At the end of every month, the International Myeloma Foundation Newsroom will feature a wrap-up of some of the most fascinating studies about multiple myeloma from medical journals. Here is the July 2025 edition.

The IMF team of medical editors has provided overviews of key studies. Yet, we encourage you to visit the actual articles in the journals for full details and to increase your understanding. Check the IMF Newsroom monthly for updates like this one.

In the Journals (Key Myeloma Research in July 2025)

"Tocilizumab Prophylaxis for Patients with Multiple Myeloma Treated with Bispecific Antibodies"

Source

Andrew Kowalski, Jillian Lykon, Benjamin T. Diamond, David G Coffey, Marcella Kaddoura, Francesco Maura, James E. Hoffman, Abhishek Pandey, Dickran Kazandjian, Carl Ola Landgren; Tocilizumab Prophylaxis for Patients with Multiple Myeloma Treated with Bispecific Antibodies. Blood Adv 2025; bloodadvances.2025016911. doi: https://doi.org/10.1182/bloodadvances.2025016911 July 1, 2025. 

Overview

Some newer treatments for multiple myeloma, called bispecific antibodies, work really well but often cause side effects like cytokine release syndrome (CRS) and ICANS reaction (a neurological side effect). CRS can cause fever, low blood pressure, or trouble breathing.

In this study, doctors gave tocilizumab—a drug usually used after CRS starts—before starting treatment, to see if it could stop CRS from happening in the first place.

They gave one dose of tocilizumab to 119 patients before their first bispecific antibody dose. The results were promising:

• Only 10% of patients had CRS, and all cases were mild (no serious or life-threatening events).
• ICANS was also low (about 6%), and similar to what’s usually seen.
• The treatment still worked well, with about 66% of patients responding.

Giving tocilizumab ahead of time may help prevent CRS without hurting how well the treatment works.

 

 

"Current Anti-Myeloma Chimeric Antigen Receptor-T Cells: Novel Targets and Methods"

Source

Vural E, Beksaç M. Current Anti-Myeloma Chimeric Antigen Receptor-T Cells: Novel Targets and Methods. Balkan Med J. 2025 Jul 1;42(4):301-310. doi: 10.4274/balkanmedj.galenos.2025.2025-4-25. 

Overview

For patients whose multiple myeloma no longer responds to standard treatments—known as triple- or penta-refractory disease—CAR-T cell therapy offers a promising new option. CAR-T stands for chimeric antigen receptor T-cell therapy. It’s a highly personalized treatment that modifies a patient’s own immune cells to better recognize and destroy myeloma cells. The process involves removing T cells from the patient’s blood, engineering them in a lab to target the cancer, growing them in large numbers, and then infusing them back into the patient after a round of mild chemotherapy.

While this therapy has shown strong results, especially when targeting a protein called BCMA found on myeloma cells, it comes with serious challenges. CAR-T treatment is complex, expensive, and only available at certain specialized centers. Producing these customized cells takes time, expertise, and tightly controlled lab conditions. Two CAR-T therapies—Abecma® (idecabtagene vicleucel, or ide-cel) and Carvykti® (ciltacabtagene autoleucel, or cilta-cel)—have been approved for relapsed or refractory myeloma and have given hope to many patients.

Still, not all patients benefit equally. CAR-T therapy can stop working over time due to T cell exhaustion, changes in the cancer that allow it to escape detection, or interference from the tumor’s environment. These issues are especially common in high-risk myeloma. To overcome them, researchers are testing new strategies like dual-targeted CAR-Ts, memory-based T cells that may last longer, and combining CAR-T with immune-boosting drugs. Faster and more cost-effective production methods are also in development.

Looking ahead, scientists are exploring whether CAR-T could be used earlier in treatment, possibly even replacing stem cell transplants for some patients. While it’s not yet a perfect solution, CAR-T therapy represents a major shift in how we approach multiple myeloma. It offers new hope for patients with limited options, even as researchers continue working to improve access, effectiveness, and long-term results.

 

 

"Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential"

Source

Kotulová, J., Baďurová, K., Chyra, Z. et al. Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential. Biomark Res 13, 92 (2025). https://doi.org/10.1186/s40364-025-00799-7 July 1, 2025. 

Overview

Multiple myeloma is a complex blood cancer driven by genetic changes and changes in the tumor’s environment. While current treatments have improved survival, they often target the same set of antigens—proteins like BCMA, CD38, SLAMF7, and GPRC5D that appear on the surface of myeloma cells. Over time, some patients develop resistance to these therapies, or their cancer cells change to avoid being recognized—a process called antigen escape. Treatments can also affect healthy cells by mistake, leading to unwanted side effects known as off-tumor toxicity.

To solve these problems, researchers are now using advanced tools like surface proteomics and integrative “omics” (a way of studying genes and proteins together) to discover new, more precise targets. These new targets are proteins found mostly on cancer cells and less so on healthy cells, which may help reduce side effects and lower the chances of relapse. This recent review highlights fifteen of these promising targets that are either in early human trials or being tested in the lab. Among them, LILRB4, SEMA4A, ITGB7, CCR1, and CD70 stand out for their potential.

These new targets are being studied as part of next-generation immunotherapies, such as antibody–drug conjugates, bispecific antibodies, and CAR-T cell therapy. Early studies suggest these treatments may be safer and more effective, thanks to their ability to zero in on cancer cells while avoiding healthy tissues. Some also show ways to work around immune resistance, a major hurdle in treating advanced myeloma.

By mapping out the biology of these targets and how they contribute to myeloma’s growth and survival, researchers are building the foundation for future therapies. This work brings hope for treatments that are not only more powerful but also gentler on the body, with the ultimate goal of improving outcomes for people living with multiple myeloma.

 

 

"CALR regulates the proliferation and drug sensitivity of multiple myeloma cells through the BCL2 signaling pathway"

Source

Wang, Y., Hu, X., Song, Y. et al. CALR regulates the proliferation and drug sensitivity of multiple myeloma cells through the BCL2 signaling pathway. Mol Biol Rep 52, 664 (2025). https://doi.org/10.1007/s11033-025-10749-z July 1, 2025. 

Overview

Researchers are continuing to study what makes multiple myeloma grow and how to make treatments more effective. One protein they’re looking at is calreticulin (CALR), which has been linked to the development of other types of cancer. Until now, its role in multiple myeloma wasn’t well understood.

In this study, scientists found that CALR levels are higher than normal in myeloma cells. When they reduced CALR in these cells—both in lab tests and in animal models—the cancer cells grew more slowly, responded better to the drug Velcade® (bortezomib), and were more likely to die off. The results suggest that CALR helps myeloma cells survive and resist treatment.

Further testing showed that lowering CALR seems to activate the cell’s natural self-destruct process (called apoptosis), possibly by affecting a pathway linked to a protein called BCL2, which helps cells avoid death. This discovery could be important for improving treatment.

In short, this research suggests that targeting CALR might help slow myeloma growth and make current treatments, like bortezomib, work better. More research is needed, but it offers a potential new path for therapy.

 

 

"Exploring what matters most to patients in relapsed refractory multiple myeloma treatment: a Canadian discrete choice experiment with patients, caregivers and physicians"

Source

Hall, R., Chua, G.N., Macfarlane, B. et al. Exploring what matters most to patients in relapsed refractory multiple myeloma treatment: a Canadian discrete choice experiment with patients, caregivers and physicians. BMC Cancer 25, 1095 (2025). https://doi.org/10.1186/s12885-025-14490-5 July 1, 2025.  

Overview

For people living with relapsed or refractory multiple myeloma (RRMM), choosing a treatment often means weighing tough trade-offs between side effects and the hope of longer survival. A new Canadian study looked at what patients value most when making these decisions and how closely caregivers and healthcare providers understand those preferences.

The study asked over 100 patients, along with caregivers and healthcare professionals, to compare different treatment options. These included both CAR-T cell therapy and conventional treatments. Participants were given a series of choices between made-up treatment scenarios that varied in five areas: how long the cancer stayed under control (progression-free survival), the chance of being alive in 10 years, the risk of serious side effects, the risk of long-term moderate side effects, and how the treatment was given (like by IV or injection).

Across the board, the most important factors for patients were longer survival and keeping the cancer from coming back. They were willing to accept a higher risk of side effects if it meant a better chance of living longer. Interestingly, long-term moderate side effects—like nerve pain or fatigue—were more concerning than short-term serious ones. How the treatment was given mattered the least. Caregivers and healthcare providers were generally in tune with what patients prioritized.

While patients didn’t strongly prefer how CAR-T therapy is administered compared to standard options, they did favor it for its potential to improve survival and reduce long-term side effects. These insights could help guide treatment decisions and shape how new therapies like CAR-T are offered and covered in Canada.

 

 

"Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting"

Source

Zhang, Q., Song, Y., Zhou, K. et al. Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting. Biomark Res 13, 90 (2025). https://doi.org/10.1186/s40364-025-00803-0 July 1, 2025. 

Overview

At the 2024 ASH Annual Meeting, researchers shared exciting progress in treating relapsed or refractory multiple myeloma, especially for patients who have already been through many rounds of treatment. These updates focused on new drugs with unique ways of attacking the disease, including novel antibodies, T-cell engagers, and next-generation versions of existing therapies. Many of these treatments were tested in combination for the first time, showing encouraging results.

One promising therapy is Cevostamab, which targets a protein called FcRH5. It showed a 30% response rate in patients who had already been treated with BCMA-targeted therapies and over 60% in patients who hadn’t. A new dosing approach helped lower the risk of cytokine release syndrome, a common side effect. Lisaftoclax, a drug that blocks BCL-2 (a protein that helps cancer cells survive), showed strong response rates—ranging from 61% to 100%—when used in combination with other treatments, with many patients achieving deep responses.

Other updates included Inobrodib, the first oral epigenetic drug shown to overcome resistance to pomalidomide, achieving a 71% response rate when combined with lenalidomide. Elrexfio (elranatamab), a BCMA-targeting bispecific antibody, combined with carfilzomib and dexamethasone, showed an 83% response rate with responses lasting longer than the study follow-up period. Mezigdomide, a new generation CELMoD, had an 86% response rate and a progression-free survival of nearly 18 months in patients whose cancer was resistant to lenalidomide.

A standout in the new wave of therapies is ISB 2001, a tri-specific antibody that targets BCMA, CD38, and CD3 all at once. In heavily pretreated patients, it achieved a 90% response rate with only mild side effects.

Together, these advances signal a shift toward more targeted, longer-lasting, and personalized treatments for multiple myeloma. By combining therapies and finding ways to overcome drug resistance, doctors are getting closer to giving patients better outcomes and more treatment options, even in the most challenging cases.

 

 

"MASS-4 is more suitable than MASS-3 for prognostic stratification in transplant-eligible patients with newly diagnosed multiple myeloma"

Source

Yang, F., Liu, J., Gu, J., Chen, M., Huang, B., Kuang, L., & Li, J. (2025). MASS-4 is more suitable than MASS-3 for prognostic stratification in transplant-eligible patients with newly diagnosed multiple myeloma. Annals of Medicine, 57(1). https://doi.org/10.1080/07853890.2025.2519671 July 1, 2025. 

Overview

Doctors use staging systems to help predict how multiple myeloma will progress and how well a patient might respond to treatment. In China, the Mayo Additive Staging Systems (MASS-3 and MASS-4) have been useful for patients with newly diagnosed multiple myeloma (NDMM), but it wasn't clear how well they worked for patients healthy enough to undergo a stem cell transplant.

This study looked back at the records of 215 transplant-eligible patients treated between 2013 and 2022. All of them received induction therapy followed by an autologous stem cell transplant (ASCT). Researchers compared how well MASS-3 and MASS-4 predicted patient outcomes, including how long patients lived without their cancer getting worse (progression-free survival, or PFS) and how long they lived overall (overall survival, or OS).

The results showed that MASS-4 did a better job than MASS-3 at identifying which patients were likely to have worse outcomes. For example, in MASS-4, patients in the highest risk group had a median overall survival of just 41 months, compared to over 100 months in lower-risk groups. MASS-4 also helped spot high-risk patients who wouldn’t have been identified using the older R-ISS staging system.

Interestingly, in patients who received tandem transplants (two back-to-back transplants), there was no major difference in outcomes between the stages. This suggests that tandem ASCT might help overcome poor prognosis in high-risk patients.

Overall, this study supports the use of MASS-4 as a more accurate way to predict outcomes in transplant-eligible multiple myeloma patients and helps guide decisions on who may need more aggressive treatment.

 

 

"Crystal-Storing Histiocytosis as a Red Herring in Multiple Myeloma"

Source

Basu, A., Rath, A., Vinarkar, S. et al. Crystal-Storing Histiocytosis as a Red Herring in Multiple Myeloma. Indian J Hematol Blood Transfus (2025). https://doi.org/10.1007/s12288-025-02080-1  July 1, 2025. 

Overview

Multiple myeloma (MM) is a cancer of plasma cells that can cause damage to organs by producing abnormal proteins. In rare cases, these proteins can form crystals inside immune cells called histiocytes, leading to a condition known as crystal-storing histiocytosis (CSH). It’s even more unusual for MM, CSH, and amyloidosis—another condition where abnormal proteins build up in tissues—to all occur in the same patient. This case report describes one of these rare instances.

A 56-year-old man came to the hospital with chronic lower back pain and high levels of creatinine, a marker of kidney trouble. Testing showed signs of multiple myeloma, including high beta-2 microglobulin, abnormal immunoglobulin levels, and changes in his blood. A bone marrow test showed both myeloma cells and histiocytes filled with protein crystals. Further testing confirmed the presence of amyloid deposits in the blood vessels—signs of amyloidosis.

This combination of MM, CSH, and amyloidosis is extremely rare and can make diagnosis more difficult. For example, the crystal-storing histiocytes can hide or mask the number of myeloma cells, making it seem like there are fewer cancer cells than there really are.

The patient began treatment with Velcade® (bortezomib)-based chemotherapy, and after three cycles, he achieved a very good partial response—meaning his cancer has significantly improved but isn’t completely gone. This case shows the importance of recognizing unusual features like CSH in order to accurately diagnose and treat multiple myeloma.

 

 

"Cardiac biomarkers for risk stratification in newly diagnosed high-risk multiple myeloma in the GMMG-CONCEPT trial"

Source

Leypoldt, L.B., Guo, L., Besemer, B. et al. Cardiac biomarkers for risk stratification in newly diagnosed high-risk multiple myeloma in the GMMG-CONCEPT trial. Cardio-Oncology 11, 63 (2025). https://doi.org/10.1186/s40959-025-00358-x   July 3, 2025.  

Overview

In a recent study, researchers looked at how certain heart-related blood markers might help predict heart problems in patients with high-risk multiple myeloma who are starting treatment with a four-drug combination that includes Kyprolis® (carfilzomib). Carfilzomib is known to sometimes cause heart-related side effects, so finding ways to identify who is most at risk could help improve care.

The study followed 126 patients and monitored two heart markers in the blood: NT-proBNP and high-sensitive Troponin I (hsTropI). Most patients—about three out of four—already had high NT-proBNP levels before treatment began. However, these elevated levels didn’t help predict who would go on to develop heart problems during treatment. On the other hand, even slightly higher levels of hsTropI at the start of treatment were linked to a higher risk of cardiovascular events.

The key takeaway: patients with very low hsTropI levels before treatment were much less likely to experience heart issues. This suggests hsTropI could be a useful tool to help doctors identify patients at lower risk for heart complications during treatment with carfilzomib.

 

 

"Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial"

Source

Aurore Perrot, Cyrille Touzeau, Jerome Lambert, Cyrille Hulin, Denis Caillot, Lionel Karlin, Bertrand Arnulf, Philippe Rey, Laurent Garderet, Margaret Macro, Martine Escoffre Barbe, Julie Gay, Thomas Chalopin, Romain Gounot, Jean-Marc Schiano, Mourad Tiab, Mohamad Mohty, Frederique Kuhnowski, Jean Fontan, Salomon Manier, Frederique Orsini-Piocelle, Laure Vincent, Sophie Rigaudeau, Xavier Leleu, Benjamin Hebraud, Laurent Flet, Jean-Valere Malfuson, Caroline Jacquet, Driss Chaoui, Nathalie Meuleman, Wajed Abarah, Lydia Montes, Riad Benramdane, Cecile Sonntag, Hacene Zerazhi, Alina Danu, Olivier Allangba, Mamoun Dib, Murielle Roussel, Sophie Cereja, Julien Depaus, Nicolas Branche, Helene Demarquette, Valentine Richez, Brieuc Cherel, Laurent Frenzel, Marie-Christiane Vekemans, Noemie Bigot, Herve Avet-Loiseau, Jill Corre, Philippe Moreau; Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial. Blood 2025; 146 (1): 52–61. doi: https://doi.org/10.1182/blood.2024026230  July 3, 2025. 

Overview

For patients newly diagnosed with multiple myeloma who are eligible for a stem cell transplant, starting treatment with a four-drug combination is the standard approach. The MIDAS study looked at how well one of these combinations—Sarclisa® (isatuximab), Kyprolis® (carfilzomib), Revlimid® (lenalidomide), and dexamethasone (called IsaKRD)—worked as induction therapy before transplant. The study included 791 patients, with a median age of 59, and followed them through six 28-day treatment cycles.

The results were promising. Most patients (96%) completed all six cycles, and 94% were able to collect enough stem cells for a possible tandem (two-step) transplant. About 91% of patients had a very good partial response or better, and 63% showed no detectable cancer cells (MRD-negative) at a sensitive testing level. Only 7 patients had their disease get worse during this phase, and 5 died—mostly from disease or heart-related issues.

Serious side effects were mostly related to low white blood cells, low platelets, and infections. Peripheral neuropathy, a common concern with myeloma treatments, was reported at any level in just 13% of patients. Overall, IsaKRD induction led to strong early responses, deep remission, and successful stem cell collection, with a safety profile in line with what’s already known. Longer-term follow-up is ongoing to see how well these results hold up over time.

 

 

"Are we ready for an MRD-driven approach in multiple myeloma?"

Source

Francesca Gay, Roberto Mina; Are we ready for an MRD-driven approach in multiple myeloma?. Blood 2025; 146 (1): 2–4. doi: https://doi.org/10.1182/blood.2024028273  July 3, 2025. 

Overview

The MIDAS study is testing a new way to treat patients with newly diagnosed, transplant-eligible multiple myeloma—one that’s based on how well their disease responds early in treatment, rather than just their risk at diagnosis. The early results are promising: about two-thirds of patients reached MRD negativity after induction therapy with a four-drug combination called IsaKRd (isatuximab, carfilzomib, lenalidomide, and dexamethasone). MRD negativity means no detectable myeloma cells using very sensitive tests, and it’s linked to better long-term outcomes.

What makes MIDAS different is its goal to personalize treatment. Instead of treating every patient the same way, the study will now split patients into different groups based on whether or not they reach MRD negativity. Those who are MRD-negative may be able to skip a stem cell transplant, while those who are MRD-positive may need more intensive treatment, like a second transplant. The idea is to give each patient just the right amount of therapy—enough to be effective, but not so much that it causes unnecessary side effects or cost.

The MIDAS study also shows that using MRD to guide treatment decisions is realistic. Over 99% of patients were able to have their MRD status checked after induction. The IsaKRd regimen led to the highest post-induction MRD-negative rates ever reported in a phase 3 trial. It was also generally well tolerated, with low rates of heart issues and nerve damage.

That said, MRD alone might not tell the whole story. Some high-risk patients still face a greater chance of relapse, even if they reach MRD negativity. For example, patients with certain genetic changes like del17p or t(11;14) didn’t respond as strongly to treatment. This raises questions about whether MRD should fully replace genetic risk factors when making treatment decisions. Another open question is how sensitive MRD testing needs to be—tests that detect one cancer cell among a million (10⁻⁶) might be better than those that detect one in 100,000 (10⁻⁵), but they are also harder to do consistently.

In short, MIDAS is a major step toward more tailored, response-driven treatment in multiple myeloma. As the study continues, it may help redefine the standard of care, where MRD, not just a patient’s diagnosis or biology, helps guide the path forward.

 

 

"Identification and validation of the m6A-binding protein LRPPRC to promote tumorigenesis in multiple myeloma"

Source

Tang, J., Li, J., Qin, S., Xiao, Y., Liu, J., Chen, X., & Zhang, Y. (2025). Identification and validation of the m6A-binding protein LRPPRC to promote tumorigenesis in multiple myeloma. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2523082 July 3, 2025.  

Overview

Researchers are studying a protein called LRPPRC to understand its role in multiple myeloma and whether it could help predict how the disease will behave. This protein is linked to m6A, a chemical change in RNA that affects how cells grow and survive. The study looked at LRPPRC levels in both lab-grown myeloma cells and bone marrow samples from patients.

They found that LRPPRC was present at higher levels in myeloma patients compared to healthy individuals, and the amount of this protein went up with more advanced stages of the disease. Patients with higher LRPPRC levels tended to have a worse outlook. When researchers reduced LRPPRC levels in myeloma cells in the lab, the cancer cells grew more slowly, were more likely to die, and showed signs of being stuck in an earlier phase of the cell cycle.

LRPPRC seems to help myeloma cells grow and survive. This makes it a potential marker for how aggressive a patient’s myeloma might be.

 

 

"Large-scale dependency and drug screens to characterize the therapeutic vulnerabilities of multiple myeloma with 1q"

Source

Romanos Sklavenitis-Pistofidis, Elizabeth D. Lightbody, Mairead Reidy, Junko Tsuji, Jean-Baptiste Alberge, Michelle P. Aranha, Daniel Heilpern-Mallory, Harvey G. Roweth, Daisy Huynh, Stephen J. F. Chong, Anna Y. Chung, Jeremy Zhang, Liam Hackett, Nicholas J. Haradhvala, Ting Wu, Nang K. Su, Brianna Berrios, Saveliy Belkin, Ankit K. Dutta, Ryan A. Knudson, Carolyn Brandt, Patricia T. Greipp, Matthew S. Davids, Maria Papaioannou, Gad Getz, Irene M. Ghobrial, Salomon Manier; Large-scale dependency and drug screens to characterize the therapeutic vulnerabilities of multiple myeloma with 1q+. Blood 2025; 146 (1): 89–103. doi: https://doi.org/10.1182/blood.2024025102  July 3, 2025. 

Overview

For many people with multiple myeloma, new targeted treatments are limited because most patients don’t have genetic changes that can be easily targeted with drugs. However, a common genetic feature called “1q gain” or “1q+” is found in a large number of myeloma cases. This means there are extra copies of part of chromosome 1, and it's linked to faster disease progression and worse outcomes. Because 1q+ is so common, finding therapies that work specifically for this group could help many patients.

In this study, researchers looked for weak spots in myeloma cells with 1q+ by testing different drugs and analyzing how the cells responded. They found that these cells were more sensitive to drugs that block two specific proteins: MCL1 and PI3K, both of which help cancer cells grow and survive. Using advanced techniques like single-cell RNA sequencing, the team showed that cells with 1q+ had higher activity in both the MCL1 and PI3K pathways compared to cells without this genetic change, even when the cells came from the same patient.

They also confirmed these results by testing lab-grown myeloma cells engineered to have or not have the 1q+ feature. Again, the cells with 1q+ were more vulnerable to the same two types of drugs. Even more encouraging, when MCL1 and PI3K inhibitors were used together, the effect was even stronger, stopping the cancer cells from growing further.

These findings suggest that patients with 1q+ multiple myeloma may respond especially well to MCL1 and PI3K inhibitors—possibly even at lower doses. This could lead to safer, more effective treatments for a large group of patients who currently face limited options.

 

 

"Another 1q bites the dust"

Source

Vikas A. Gupta, Lawrence H. Boise; Another 1q bites the dust. Blood 2025; 146 (1): 7–8. doi: https://doi.org/10.1182/blood.2025028903 July 3, 2025.  

Overview

Researchers are working to improve treatment options for people with multiple myeloma who have a genetic change called “gain of 1q,” which means there are extra copies of a part of chromosome 1. This genetic change is found in about 40% of newly diagnosed patients and is linked to worse outcomes, especially when it shows up as a stronger version called 1q amplification. Because it's so common and tied to higher risk, finding ways to target 1q is an important step toward more effective, personalized care.

In a recent study, scientists used powerful lab tools, including CRISPR gene editing and drug screening, to search for weak spots in myeloma cells with 1q gain. They discovered that these cells are especially sensitive to drugs that block two key proteins: MCL1 and PI3K. These proteins help myeloma cells grow and survive. When researchers treated 1q+ cells with MCL1 or PI3K inhibitors—especially when both were used together—the cancer cells stopped growing.

They also studied how these drugs work on a deeper level. MCL1 blockers appeared to freeze cells in a phase of the cell cycle where they normally prepare to divide. PI3K blockers seemed to shut down stress-related proteins and parts of the cell’s internal support structure. Together, these effects weakened the cancer cells without necessarily killing them right away—what scientists call a cytostatic effect.

Although MCL1 and PI3K inhibitors have been tested before in multiple myeloma, they haven’t been very successful on their own, partly because of side effects like heart issues. But the discovery that 1q+ cells are extra sensitive to these drugs means they might work well at lower doses, which could help avoid those side effects.

The research also raises important questions. Will these drugs work equally well in patients who have other common myeloma-related genetic changes, like t(11;14) or del(17p)? Will they be enough to control the full range of myeloma cells in the body, or will they need to be combined with standard treatments? And could increasing levels of MCL1 in the cancer eventually make even these drugs less effective?

Overall, this research is an exciting step toward personalized treatment for a large group of myeloma patients. By focusing on the biology of 1q gain, scientists are paving the way for more targeted therapies that could be both safer and more effective.

 

 

"Loss of BCL7A permits IRF4 transcriptional activity and cellular growth in multiple myeloma"

Source

Chandraditya Chakraborty, Srikanth Talluri, Moritz Binder, Eugenio Morelli, Jessica Encinas Mayoral, Sanika Derebail, Anil Aktas Samur, Charles Epstein, Kenneth C. Anderson, Masood Shammas, Mehmet K. Samur, Mariateresa Fulciniti, Nikhil C. Munshi; Loss of BCL7A permits IRF4 transcriptional activity and cellular growth in multiple myeloma. Blood 2025; 146 (1): 104–114. doi: https://doi.org/10.1182/blood.2024026588  July 3, 2025. 

Overview

Multiple myeloma is a complicated blood cancer with many genetic changes, but until recently, researchers hadn't found one common mutation that showed up in a large number of patients. In this new study, scientists used whole-genome sequencing and discovered that about 62% of people with multiple myeloma have mutations in a specific area of a gene called BCL7A. This region doesn’t code for proteins directly, but it plays a big role in controlling how the gene functions.

They also found that BCL7A is barely active in most myeloma cells compared to healthy plasma cells. When researchers turned off BCL7A in lab-grown myeloma cells, the cancer cells grew faster. But when they forced the cells to express BCL7A again, the cancer cells became weaker and less able to survive. This suggests that BCL7A acts like a tumor suppressor—a gene that normally helps keep cancer in check.

Digging deeper, they discovered that BCL7A works with another key protein called IRF4, which helps define what makes a plasma cell. Normally, BCL7A keeps IRF4 from activating too many genes that help cancer cells grow. But when BCL7A is lost, IRF4 becomes more active, increasing the production of growth-promoting signals while also lowering energy use and stress signals in the cells. In short, losing BCL7A gives myeloma cells more power to grow and survive.

This research points to BCL7A as a major piece of the puzzle in how multiple myeloma develops—and may one day lead to new treatment strategies that restore its tumor-suppressing effects.

 

 

"Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury"

Source

E. Bridget Kim, Jack E. Malespini, Matthew Lei, Samuel S. Han, Cole W. Minsky, Andrew R. Branagan, Elizabeth K. O’Donnell, Diana Cirstea, Noopur S. Raje, Andrew J. Yee; Early daratumumab therapy improves renal outcomes in newly diagnosed patients with myeloma admitted with kidney injury. Blood Adv 2025; 9 (13): 3129–3135. doi: https://doi.org/10.1182/bloodadvances.2025015901 July 8, 2025. 

Overview

Cast nephropathy is the leading cause of acute kidney injury (AKI) in people newly diagnosed with multiple myeloma (MM), and reversing kidney damage quickly is crucial for better outcomes. This study looked at 20 patients with MM and AKI who were treated with a daratumumab-based therapy. Daratumumab is a monoclonal antibody that targets CD38 and is known to be effective in treating MM.

The results were strong: all patients showed at least a 50% drop in serum free light chains (sFLCs)—a key marker of disease—within the first cycle of treatment, and it happened fast, with a median time of just 3 days. Most patients also brought their sFLC levels down to 500 mg/L or less within two weeks. After three months, 85% of patients had some level of kidney recovery, and half had full recovery. Of the patients who started on dialysis, more than half were off dialysis by three months, and nearly all were dialysis-free by a year.

The treatment also worked well against the cancer itself. Every patient responded, with 90% reaching a very good partial response or better. After a median follow-up of just over two years, most patients were still alive, and many had not yet seen their disease return. These results show that starting daratumumab-based therapy early in patients with MM and AKI can quickly lower toxic light chain levels, improve kidney function, and possibly avoid the need for plasmapheresis.

 

 

"Comprehensive machine learning analysis of PANoptosis signatures in multiple myeloma identifies prognostic and immunotherapy biomarkers"

Source

Feng, Y., Wang, S., Zhang, J. et al. Comprehensive machine learning analysis of PANoptosis signatures in multiple myeloma identifies prognostic and immunotherapy biomarkers. Sci Rep 15, 22478 (2025). https://doi.org/10.1038/s41598-025-06376-0 July 2, 2025. 

Overview

Researchers are exploring a new way to understand and treat multiple myeloma by looking at a process called PANoptosis—a form of programmed cell death that may affect how cancer starts and responds to treatment. While its role in myeloma hasn’t been clear, this study used large sets of patient data and advanced machine learning tools to find seven key PANoptosis-related genes (PRGs) that could help predict patient outcomes.

The scientists built a risk model based on these genes and tested it in multiple groups of patients. It consistently identified high-risk individuals—those whose cancer had more mutations, fewer healthy immune cells in the tumor, and greater tumor “purity,” meaning more cancer cells and fewer normal cells. These high-risk patients also showed increased sensitivity to several drugs, including cyclophosphamide, Sinularin, Wee1 inhibitors, and others, suggesting this model could help guide personalized treatment choices.

Further testing showed that some of the key genes—PARP1, ZBP1, LY96, and CASP3—were especially active in myeloma plasma cells. These findings were confirmed using lab techniques like qPCR and tissue staining. In particular, PARP1 was shown to play a big role in helping myeloma cells survive.

In short, this new PANoptosis-based model offers a promising way to predict how multiple myeloma might progress and to tailor treatment more precisely for each patient.

 

 

"The impact of high-risk cytogenetics on treatment efficacy and outcomes of patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis of randomized controlled trials"

Source

Ntanasis-Stathopoulos, I., Filippatos, C., Malandrakis, P. et al. The impact of high-risk cytogenetics on treatment efficacy and outcomes of patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis of randomized controlled trials. Leukemia (2025). https://doi.org/10.1038/s41375-025-02677-5 July 2, 2025. 

Overview

Certain genetic changes in multiple myeloma—like translocations t(4;14), t(14;16), and deletion of part of chromosome 17 (known as del(17p))—are usually seen as “high-risk” because they’re linked to worse outcomes in newly diagnosed patients. But it’s been less clear how these high-risk features affect patients whose myeloma has come back or stopped responding to treatment, known as relapsed/refractory multiple myeloma (RRMM).

To better understand this, researchers reviewed 28 clinical trials that compared treatment results between patients with high-risk and standard-risk genetics. They looked at how long patients lived without their disease getting worse (progression-free survival) and overall survival. The results showed that, overall, having high-risk genetic features didn’t lead to worse outcomes in RRMM. In other words, these patients seemed to respond to treatment similarly to those without high-risk genetics.

One interesting observation was that patients with high-risk genetics who received anti-BCMA therapies (a newer type of treatment) may have had slightly better results, but the difference wasn’t large enough to be considered statistically significant. Among all the genetic changes studied, del(17p) appeared to have the biggest potential impact on how well treatments worked, though again, the data wasn’t strong enough to confirm this.

The main takeaway is that, in the setting of relapsed or refractory myeloma, traditional high-risk genetic markers may not be as useful in predicting how well patients will respond to treatment. This highlights the need for better tools to guide treatment decisions when myeloma returns.

 

 

"Landscapes of immunoglobulin heavy-chain gene repertoire and its cytogenetic abnormalities in Chinese patients with multiple myeloma"

Source

Gong, Y., Tao, T., Zhou, M. et al. Landscapes of immunoglobulin heavy-chain gene repertoire and its cytogenetic abnormalities in Chinese patients with multiple myeloma. Sci Rep 15, 22837 (2025). https://doi.org/10.1038/s41598-025-04158-2 July 2, 2025. 

Overview

Multiple myeloma (MM) is a complex cancer, and researchers are still working to fully understand how it develops. B-cell receptors, which are involved in how the immune system responds to threats, are known to play an important role in the disease. However, the genetic details behind this process—especially in Chinese patients—haven’t been well studied.

In this research, scientists looked at the immunoglobulin heavy-chain (IGH) gene rearrangements in 301 Chinese patients who were newly diagnosed with MM. They used next-generation sequencing (NGS) and checked for chromosomal changes using FISH testing. They discovered that one gene, IGHV4-39, showed up much more often than expected. This gene was linked to a higher rate of mutation and shorter HCDR3 regions, both of which may influence how the cancer behaves.

Importantly, IGHV4-39 was also strongly connected to high-risk genetic changes, especially the t(4;14) translocation, which is known to signal a more aggressive form of MM. This study is the largest of its kind in Asia and is the first to show a connection between specific IGHV genes and high-risk features in Chinese MM patients.

 

 

"Optimized strategy to mitigate daratumumab interference in blood bank testing: Reducing cost and time"

Source

Tom Yu, Antonio Insigne, Walia Anushka, Elena Nedelcu, Optimized strategy to mitigate daratumumab interference in blood bank testing: Reducing cost and time, American Journal of Clinical Pathology, 2025;, aqaf060, https://doi.org/10.1093/ajcp/aqaf060  July 2, 2025. 

Overview

Patients with multiple myeloma who are treated with daratumumab (DARA) often need blood transfusions, but DARA can interfere with standard blood testing. This interference makes it harder for doctors to ensure that the blood a patient receives is a safe match. Current guidelines say patients should have their red blood cell type checked before starting DARA, but there's no standard process for testing once treatment begins.

This study looked at nearly a decade of data from 850 multiple myeloma patients who were treated with DARA. About 20% of them received at least one blood transfusion. The researchers tested each patient’s blood before and after DARA treatment. After receiving DARA, every patient showed a reaction in the lab known as a "panagglutinin" — a common effect of the drug — but none developed dangerous new antibodies that would complicate transfusions.

The team also compared different testing strategies. They found that by using a more efficient approach, they could reduce both the time it took to prepare for a transfusion and the cost, without increasing risk to patients. In short, this large study confirmed that DARA doesn't raise the risk of serious immune reactions during transfusions, and it offers a safer, more cost-effective way to manage blood testing in these patients.

 

 

"Development and Validation of a Patient-Reported Outcome Measure to Assess the Impact of Steroids in the Treatment of Myeloma: The Steroid Symptom Questionnaire–Multiple Myeloma"

Source

Tracy King, Louise Acret, Claudia Rutherford, Margaret-Ann Tait, Jacqueline Jagger, Julija Sipavicius, Georgia McCaughan, Douglas Joshua, Kate White, Development and Validation of a Patient-Reported Outcome Measure to Assess the Impact of Steroids in the Treatment of Myeloma: The Steroid Symptom Questionnaire–Multiple Myeloma, Seminars in Oncology Nursing, 2025, 151943, ISSN 0749-2081, https://doi.org/10.1016/j.soncn.2025.151943. July 2, 2025.  

Overview

Steroids are a common part of treatment for multiple myeloma, but they often cause side effects that can affect how patients feel and function day to day. Until now, there wasn’t a specific tool to measure how these steroid side effects impact people with multiple myeloma. To address this, researchers created and tested a new questionnaire called the Steroid Symptom Questionnaire–Multiple Myeloma (SSQ-MM).

The team started by reviewing existing research and talking to patients, caregivers, and doctors to understand the most important and common steroid-related symptoms. They then developed a draft version of the SSQ-MM and tested it with a group of patients to make sure it was clear, relevant, and easy to use. After refining it, they tested the final version with a larger group of 140 patients across multiple treatment centers.

The final SSQ-MM has 20 questions that cover a range of symptoms. The tool was shown to be reliable and accurate in measuring how steroids affect patients. It also worked well when compared to other standard quality-of-life surveys and could tell the difference between patients with more or fewer side effects.

In short, the SSQ-MM is now a validated way for doctors and researchers to better understand how steroids impact patients with multiple myeloma. It can help guide treatment decisions, like whether a patient might benefit from a lower steroid dose to feel better overall.

 

 

"Deciphering the dynamics of histone acetylation and chromatin remodeling in multiple myeloma: a tale beyond the tails"

Source

Sinan Xiong, Jianbiao Zhou, Wee Joo Chng; Deciphering the dynamics of histone acetylation and chromatin remodeling in multiple myeloma: a tale beyond the tails. Blood 2025; blood.2025028403. doi: https://doi.org/10.1182/blood.2025028403 July 3, 2025. 

Overview

While genetic changes play a key role in multiple myeloma, they don’t fully explain why patients respond so differently to treatment or why the disease behaves in such varied ways. New research shows that epigenetic changes—which affect how genes are turned on or off without altering the DNA itself—also play a major role in how myeloma develops and how it resists treatment.

These epigenetic changes can lead to instability in how cells read their genetic instructions, helping cancer cells survive, adapt, and resist both targeted treatments and immunotherapy. One major focus is on how changes to histones—proteins that help package DNA—can influence vital processes like DNA repair and cell survival. When these histone modifications go wrong, they can make the disease harder to treat.

Because of this, researchers are exploring new therapies that target these epigenetic mechanisms. This includes drugs aimed at HDACs, CBP/p300, and BET proteins—key players in controlling gene activity. This area of research is still growing, but it offers hope for more precise and effective treatments for multiple myeloma, especially in cases where standard therapies aren’t working.

 

 

"Beneficial effects of aerobic exercises on multiple myeloma: Mechanisms and clinical observations"

Source

He S, Wen J, Zou Z, et al. Beneficial effects of aerobic exercises on multiple myeloma: Mechanisms and clinical observations. Int J Cancer. 2025; 1-11. doi:10.1002/ijc.70032  July 4, 2025. 

Overview

Research into how exercise affects multiple myeloma treatment has had mixed results, but a recent study is shedding new light on the potential benefits. In this study, scientists looked at both mice with multiple myeloma and real patients to see if regular aerobic exercise could improve treatment outcomes.

In the lab, mice with myeloma were treated with two common drugs—bortezomib and dexamethasone—while also following a six-week aerobic exercise routine on a treadmill. The mice that exercised lived over 10 days longer on average than those that didn’t. Their immune systems also responded differently: they had fewer regulatory T cells (which can suppress the immune response) and more natural killer (NK) cells (which help attack cancer). Exercise also boosted two proteins, IL-15 and irisin, which may help the body fight the cancer more effectively.

To see if this holds true in humans, researchers looked back at data from 65 patients receiving maintenance therapy for multiple myeloma at West China Hospital. They found that patients who followed the World Health Organization’s guidelines for physical activity had longer periods without their cancer progressing.

The study suggests that regular, moderate aerobic exercise may help support the immune system and improve how well some people respond to myeloma treatment. While more research is needed, exercise could be a helpful addition to treatment plans for some patients.

 

 

"Practical Guidance on the Clinical Management of Ocular Adverse Events Associated with Belantamab Mafodotin for Patients with Relapsed/Refractory Multiple Myeloma: Latin American Expert Panel Recommendations"

Source

Hungria, V., Abello Polo, V., Corzo, A. et al. Practical Guidance on the Clinical Management of Ocular Adverse Events Associated with Belantamab Mafodotin for Patients with Relapsed/Refractory Multiple Myeloma: Latin American Expert Panel Recommendations. Oncol Ther (2025). https://doi.org/10.1007/s40487-025-00354-2  July 4, 2025. 

Overview

Multiple myeloma remains a serious health issue around the world, especially in Latin America, where outcomes are often worse due to limited access to care. While treatments have improved in recent years, many patients eventually stop responding to standard therapies. That’s where new options like belantamab mafodotin come in.

Belantamab mafodotin is a new kind of treatment called an antibody–drug conjugate. It targets a protein found on myeloma cells, helping deliver powerful medication directly to the cancer. In two recent clinical trials—DREAMM-7 and DREAMM-8—this drug showed strong results in patients whose myeloma had come back or stopped responding to treatment. However, some patients did experience eye-related side effects, which are common with this type of drug.

To help doctors safely use belantamab mafodotin in Latin America, a team of experts from Argentina, Brazil, Colombia, and Mexico came together to create clear, practical guidelines. These recommendations cover how to spot and manage eye problems, how different specialists should work together, and how to keep patient care front and center. The goal is to make sure patients across the region can benefit from this promising new treatment safely and effectively.

 

 

"Di-(2-ethylhexyl) Phthalate (DEHP) and Its Metabolite Promote Multiple Myeloma Progression and Bortezomib Resistanc"Practical Guidance on the Clinical Management of Ocular Adverse Events Associated with Belantamab Mafodotin for Patients with Relapsed/Refractory Multiple Myeloma: Latin American Expert Panel Recommendations"

Source

Wenxia Li, Hangjie Fu, Lijian Zhu, Wei Wang, Wenli Yang, Wenbin Yang, Hua Huang, Bin Ding, Jie Sun, Hongyan Tong, Di-(2-ethylhexyl) Phthalate (DEHP) and Its Metabolite Promote Multiple Myeloma Progression and Bortezomib Resistance, Journal of Hazardous Materials, 2025,139147, ISSN 0304-3894, https://doi.org/10.1016/j.jhazmat.2025.139147. July 4, 2025.  

Overview

Di-(2-ethylhexyl) phthalate (DEHP) is a chemical commonly used to make plastics more flexible. It’s found in many everyday items—including some medical products—and can easily leak into the environment. Once inside the body, DEHP is broken down into a compound called MEHP. New research is now showing that both DEHP and MEHP may play a role in cancer growth and resistance to treatment, including in multiple myeloma.

In this study, scientists looked at how long-term exposure to DEHP affects multiple myeloma cells. They found that DEHP made the cancer cells grow faster and caused them to become resistant to bortezomib, a drug often used to treat myeloma. They discovered that DEHP activates two important pathways in the body—Wnt/β-catenin and NF-κB—that help the cancer cells survive and resist treatment. MEHP had similar effects.

These findings suggest that DEHP and its byproducts may be environmental risk factors for multiple myeloma. The results also point to potential new treatment strategies by targeting the pathways activated by DEHP. This research highlights the need to take a closer look at how DEHP exposure—especially through medical products—might affect people with myeloma and shape future health policies.

 

 

"Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma"

Source

Atanackovic, D., Luetkens, T., Schneider, D. et al. Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma. Nat Commun 16, 6154 (2025). https://doi.org/10.1038/s41467-025-60980-2  July 4, 2025.  

Overview

This study looked closely at how two types of CAR T-cell therapies—Carvykti® (ciltacabtagene autoleucel, or cilta-cel) and Abecma® (idecabtagene vicleucel, or ide-cel)—perform in real-world treatment of multiple myeloma. Researchers followed 39 patients who received one of these therapies and found that cilta-cel led to better response rates, but also came with a higher risk of unusual side effects like certain nerve problems and infections.

The study showed that cilta-cel produced more CAR T cells in the body, especially a type called CD4+ cells, which seemed to help the treatment work better. These cells were more active, showed stronger memory and immune functions, and stayed in the body longer than those from ide-cel. This longer presence was linked to a higher level of a specific receptor called IL-7R, which helps the cells survive. Lab tests confirmed that cilta-cel cells remained active even without ongoing exposure to cancer cells and had more energy to keep working.

In some patients who had nervous system side effects after cilta-cel treatment, the researchers found that CAR T cells had entered the brain and showed a unique pattern of inflammation. This suggests that while cilta-cel may be more powerful, it also requires careful monitoring for side effects.

Overall, this research helps explain the biological differences between cilta-cel and ide-cel and may help doctors make more personalized decisions when using CAR T-cell therapy to treat multiple myeloma.

 

 

"Mechanism of Brucea javanica against multiple myeloma via TNF-NF-κB signaling"

Source

Wang, Y., Zhang, A., Chen, Y. et al. Mechanism of Brucea javanica against multiple myeloma via TNF-NF-κB signaling. Sci Rep 15, 24311 (2025). https://doi.org/10.1038/s41598-025-10271-z  July 7, 2025. 

Overview

This study looked at how a natural plant extract called Brucea javanica (BJ) might help treat multiple myeloma. Researchers used lab techniques and computer modeling to explore how the active compounds in BJ affect cancer cells, and then tested their findings in multiple myeloma cell lines.

They found that BJ contains several active ingredients, with one of the most important being luteolin. Both the BJ extract and luteolin showed the ability to kill multiple myeloma cells in a dose-dependent way, meaning the higher the dose, the stronger the effect. BJ and luteolin slowed down cancer cell growth, caused the cells to self-destruct (a process called apoptosis), and stopped the cells from continuing to divide.

One key discovery was that BJ and luteolin seem to work by blocking the TNF/NF-κB signaling pathway, which is known to help cancer cells survive and grow. The treatments reduced the levels of important molecules involved in this pathway, including TNF-α and several proteins linked to inflammation and cell survival.

These findings suggest that Brucea javanica—and especially luteolin—could be promising natural compounds to explore further as part of multiple myeloma treatment, working by targeting key pathways that fuel the disease.

 

 

"Enhancing detection of central nervous system involvement in multiple myeloma: A novel multidimensional dot-plot based analysis for flow cytometry"

Source

Palicskó, B., Janovák, L., Rejtő, L., Váróczy, L., Hevessy, Z., & Kárai, B. (2025). Enhancing detection of central nervous system involvement in multiple myeloma: A novel multidimensional dot-plot based analysis for flow cytometry. Cytometry Part B: Clinical Cytometry, 1–7. https://doi.org/10.1002/cyto.b.22245  July 7, 2025. 

Overview

In rare cases, multiple myeloma can spread to the brain and spinal cord, leading to serious complications. This is called central nervous system (CNS) involvement, and it usually comes with a poor outlook. Detecting it early is critical, but current testing methods—like looking for cancer cells in spinal fluid (CSF) under a microscope—often miss cases, especially when there aren’t many cells in the sample.

This study tested a new, more advanced way to detect myeloma cells in spinal fluid using a special software tool called a multidimensional radar dot-plot, combined with an 8-color flow cytometry method. Researchers looked at 125 CSF samples from patients suspected of having CNS involvement. Out of those, 89 samples from 40 patients were closely studied.

The new method was more sensitive and accurate than the traditional one. It was able to clearly tell the difference between normal plasma cells, abnormal myeloma cells, and cell debris—even in samples with very few cells. In 25% of cases, the older method suggested cancer was present when it wasn’t, but the new method helped rule those out correctly. It was also able to detect myeloma cells in extremely diluted samples, which is important for patients with low cell counts in their spinal fluid.

This new radar dot-plot approach may help doctors spot brain and spinal cord involvement in myeloma more reliably and earlier, which could lead to better care and treatment decisions. More research in larger groups is still needed, but the results are promising.

 

"A somatic multiple myeloma mutation unravels a mechanism of oligomerization-mediated product inhibition in GGPPS"

Source

Yehia, R., Portašiková, J.M., Mor Yosef, R., Da'adoosh, B., Kádek, A., Man, P., Giladi, M. and Haitin, Y. (2025), A somatic multiple myeloma mutation unravels a mechanism of oligomerization-mediated product inhibition in GGPPS. FEBS J. https://doi.org/10.1111/febs.70181  July 7, 2025

Overview

This study looked at a key enzyme called GGPPS, which plays an important role in the growth and survival of multiple myeloma cells. GGPPS helps with a process called protein prenylation, which allows certain proteins to function properly inside cancer cells. Understanding how this enzyme works could open the door to new treatment options.

Researchers studied different forms of GGPPS to understand how its structure affects its activity. They found that the enzyme usually forms larger complexes (called hexamers) that help keep it in check. But in some myeloma cells—like the commonly used RPMI-8226 cell line—a mutation called GGPPSR235C weakens these complexes. This makes the enzyme work faster and release its products more easily, which may support cancer cell growth.

An even more unstable version of the enzyme, created in the lab, confirmed that when GGPPS can’t form stable complexes, it loses a “lid” that normally helps keep the enzyme's activity under control. These discoveries show that the shape and stability of GGPPS are key to how it behaves in myeloma cells.

Overall, this research highlights why it’s important to choose the right cell models in drug development and suggests that targeting the structure of GGPPS could be a new way to treat multiple myeloma.

 

 

"Immune Alterations in Myeloma Evolution and Outcomes: Quo Vadis?"

Source

Madhav V. Dhodapkar, Bruno Paiva; Immune Alterations in Myeloma Evolution and Outcomes: Quo Vadis?. Blood 2025; blood.2024026227. doi: https://doi.org/10.1182/blood.2024026227 July 7, 2025. 

Overview

Multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined significance (MGUS), are both linked to changes in the immune system that happen with age. MGUS is common in older adults, but only about 1% of people with it go on to develop myeloma each year. Scientists believe that long-term stress on the immune system may help trigger MGUS, and that both the innate and adaptive immune systems play a role in keeping it in check.

Recent studies show that even in the MGUS stage, the immune system begins to show signs of aging and dysfunction. As MGUS progresses to multiple myeloma, these immune changes become more complex. In multiple myeloma, not only does the tumor grow in different areas of the bone marrow, but the immune system in those regions also becomes less effective. This weakening of immune response—called immune paresis—makes it easier for cancer cells to spread and increases the risk of infections.

The immune system in people with myeloma varies a lot, and this affects how well they respond to treatments, especially those that rely on the immune system like CAR T-cell therapy or bispecific antibodies. Researchers are working to better understand these immune changes to help predict who is at higher risk of disease progression or who might respond better to certain treatments.

Going forward, improving long-term outcomes in multiple myeloma may depend on preserving or restoring immune function. This includes identifying specific immune markers that can be tracked over time and adding them into risk models to better guide treatment and prevention strategies.

 

 

"Fine particulate matter exposure is linked to worse myeloma outcomes in a diverse urban cohort."

Source

Wysota, M., Pradhan, K., Jacobs, S. et al. Fine particulate matter exposure is linked to worse myeloma outcomes in a diverse urban cohort. Blood Cancer J. 15, 115 (2025). https://doi.org/10.1038/s41408-025-01301-0  July 7, 2025. 

Overview

This study looked at how air pollution might affect survival in people with multiple myeloma. Poor air quality is linked to millions of deaths each year, including over 100,000 in the U.S. While some pollutants have decreased over time, outdoor air pollution (OAP)—especially in neighborhoods like the Bronx—remains a serious health issue. These areas, often historically redlined, face higher pollution levels and worse health outcomes.

Researchers used a new method that matched patients’ home addresses with highly detailed air pollution data. They found that long-term exposure to fine particles in the air, known as PM2.5, was linked to worse survival in myeloma patients. Interestingly, exposure to sulfate—a component of PM2.5—was tied to longer survival, though the reason for this is still unclear and needs more research.

Most earlier studies on air pollution and cancer focused on solid tumors like lung or breast cancer. This study is one of the first to look closely at blood cancers like multiple myeloma using local-level pollution data. That makes the findings more accurate and relevant for understanding how where a person lives might impact their health.

There were some limitations. The study didn’t account for people moving during the research period, and it couldn’t measure indoor or workplace pollution. Some patients had missing medical or demographic information due to gaps in older records. Also, other health factors—like genetic changes or shifts in treatment over time—weren’t fully included.

Still, the study shows a possible link between air pollution and higher myeloma death rates, especially with pollutants like PM2.5 and black carbon. These findings suggest that where you live and the air you breathe may play a bigger role in cancer outcomes than previously thought. Future research could help shape cleaner air policies that support better health for people living with myeloma and other blood cancers.

 

 

"EHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma"

Source

Dimopoulos, M.A., Terpos, E., Boccadoro, M. et al. EHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma. Nat Rev Clin Oncol (2025). https://doi.org/10.1038/s41571-025-01041-x July 7, 2025. 

Overview

Since the 2021 release of treatment guidelines for smouldering multiple myeloma (SMM) and multiple myeloma (MM), there have been major updates in how doctors stage, monitor, and treat the disease. A new international staging system—called R2-ISS—has been introduced, and new tools are now being used in clinics to better predict outcomes. These include tests for minimal residual disease (MRD), circulating plasma cells, and monoclonal proteins using mass spectrometry.

At the same time, 14 new treatment options have been approved by major health agencies like the EMA and FDA. Because of all these changes, experts from across Europe updated the previous guidelines. These new evidence-based recommendations help doctors choose the best treatments for newly diagnosed patients as well as those whose myeloma has returned or stopped responding to treatment. They also include clear advice on when and how to use the latest immunotherapies.

For patients with smouldering multiple myeloma, the guidelines offer updated strategies to identify who might benefit from early treatment. In addition, they provide recommendations for managing common complications of myeloma, like bone disease, kidney problems, and infections, as well as side effects linked to newer therapies, such as cytokine release syndrome (CRS) and neurological symptoms tied to T-cell therapies.

These updated guidelines are designed to help healthcare providers offer the most effective and personalized care based on the latest research and approved treatments.

 

"Restarting teclistamab and talquetamab after prolonged dose delay may not require re–step-up dosing"

Source

Carlyn Rose Tan, Alice Wang, David Nemirovsky, Andriy Derkach, Tala Shekarkhand, Issam Hamadeh, Kylee Maclachlan, Malin Hultcrantz, Hani Hassoun, Sham Mailankody, Alexander Lesokhin, Urvi A. Shah, Sridevi Rajeeve, Hamza Hashmi, Dhwani Patel, Ross Firestone, Eric Jurgens, Kevin Miller, Gunjan L. Shah, Michael Scordo, Heather J. Landau, Sergio A. Giralt, Neha Korde, Saad Z. Usmani; Restarting teclistamab and talquetamab after prolonged dose delay may not require re–step-up dosing. Blood Adv 2025; 9 (13): 3331–3335. doi: https://doi.org/10.1182/bloodadvances.2024015344  July 8, 2025. 

Overview

This letter to the editor shares real-world experience from Memorial Sloan Kettering on restarting teclistamab and talquetamab—two bispecific antibodies used to treat multiple myeloma—after treatment delays. These drugs are used in patients whose myeloma has stopped responding to standard therapies. They work by redirecting the immune system to attack myeloma cells, but can cause serious side effects like cytokine release syndrome (CRS) and neurotoxicity (ICANS), especially when treatment is started or restarted.

To reduce the risk of these side effects, the FDA recommends a "step-up dosing" (SUD) schedule—gradually increasing the drug dose, with premedication and hospital monitoring—especially after long breaks in treatment (more than 28 days). However, in this study, doctors looked at what happened when patients did not repeat the step-up dosing after such delays.

Out of 136 patients treated with teclistamab or talquetamab between late 2022 and mid-2024, 33 patients restarted treatment after a long break without repeating the step-up process. These breaks were often due to travel, scheduling, hospitalizations, infections, or other health issues. The median delay was just over a month.

Importantly, none of these patients experienced CRS or ICANS when restarting the therapy—even without the extra hospital precautions. Most received their doses as outpatients, and many didn’t need premedication. Only two patients had fevers after restarting, and both were due to unrelated infections (COVID-19 and pneumonia).

Most patients maintained their response to treatment or even improved after restarting, although two showed signs that their disease had progressed. These results suggest that in some patients, repeating step-up dosing may not be necessary after a treatment delay, though more research is needed to confirm this approach.

For patients and caregivers, this finding could eventually mean fewer hospital stays and simpler care plans if future guidelines are updated. But any changes to treatment should always be discussed carefully with your care team.

 

 

"Targeting proteostasis in multiple myeloma through inhibition of LTK"

Source

Våtsveen, T.K., Giliberto, M., Bjornsdottir, V. et al. Targeting proteostasis in multiple myeloma through inhibition of LTK. Leukemia (2025). https://doi.org/10.1038/s41375-025-02682-8  July 9, 2025. 

Overview

Multiple myeloma (MM) cells produce large amounts of immunoglobulin, or antibody proteins. To survive, these cells rely heavily on systems that help them manage and dispose of excess or faulty proteins—a process known as proteostasis. Current treatments, like proteasome inhibitors, target the part of this system that breaks down proteins, and they’ve been effective for many patients. However, there’s been less focus on stopping the production or release of these proteins.

This study identifies a new potential target in this process: a protein called LTK, which helps myeloma cells handle the stress of constantly producing and secreting immunoglobulins. Researchers found that by blocking LTK with drugs originally designed for a similar protein (ALK), they could disrupt this secretory process. When LTK was blocked, the proteins built up inside the cells, causing stress in the endoplasmic reticulum (ER)—a part of the cell involved in protein processing—and eventually triggered cell death in myeloma cells.

Even more promising, this approach worked in myeloma cells from patients who no longer responded to standard proteasome inhibitor treatments. This means LTK could be a powerful new treatment target for people with drug-resistant multiple myeloma.

 

 

"Myeloma interaction with bone marrow stromal cells suppresses ciliogenesis and osteogenic potential in myeloma bone disease"

Source

Ying Xie et al. Myeloma interaction with bone marrow stromal cells suppresses ciliogenesis and osteogenic potential in myeloma bone disease.Sci. Transl. Med.17,eadq2961(2025). DOI:10.1126/scitranslmed.adq2961 July 9, 2025. 

Overview

Myeloma bone disease is a common and serious complication of multiple myeloma. It happens when the bone marrow stops producing healthy bone tissue, leading to weakened bones and a higher risk of fractures. This study looked into why bone damage happens in myeloma by focusing on bone marrow stromal cells (BMSCs)—the cells that help bones grow and repair.

Researchers found that when myeloma cells are present, they interfere with a key structure in BMSCs called the primary cilium—a small antenna-like part of the cell that helps it sense its environment and send signals to promote bone formation. This disruption happens through a specific interaction between the cancer cells and BMSCs using proteins called CD40 and CD40L. When these two proteins connect, they reduce the activity of another protein called SENP1, which normally helps keep a balance in protein modification.

Without enough SENP1, another protein called OFD1 becomes overly modified and starts to build up in the wrong places, which blocks the formation of the primary cilium. As a result, the BMSCs lose their ability to sense mechanical pressure or activate important bone-growth pathways like the Hedgehog signaling pathway. This breakdown in signaling leads to less bone formation and more bone loss.

The good news is that treating mice with a CD40-blocking antibody helped reduce both bone damage and tumor growth. This suggests that targeting the CD40-SENP1-OFD1 pathway could be a promising new way to treat bone disease in multiple myeloma patients.

 

 

"Rising unmet need in multiple myeloma management after first-line treatment with DRd: expected epidemiological evolution in Italy"

Source

M. Boccadoro, R. Mercati, C. Vassallo, B. Canali, F. Fiorentino, C. Galeone, Rising unmet need in multiple myeloma management after first-line treatment with DRd: expected epidemiological evolution in Italy, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.07.001. July 9, 2025.  

Overview

In Italy, many patients with newly diagnosed multiple myeloma who aren’t eligible for a stem cell transplant are now receiving a powerful first-line treatment: daratumumab combined with lenalidomide and dexamethasone (DRd). This combination has improved outcomes, but it also creates a new challenge—what to do when the disease comes back.

Currently, there are only three approved second-line treatments in Italy for patients whose myeloma returns after DRd. This is especially limiting for patients who are now resistant to lenalidomide, a key drug in the DRd combo. As more patients start DRd as their first treatment, more will eventually need a second-line therapy—but options remain limited.

Researchers used a model to estimate how many patients would face this issue in the coming years. They found that between 2025 and 2027, around 1,743 patients in Italy are expected to progress to second-line treatment after receiving DRd as their first therapy.

This highlights a growing unmet medical need in multiple myeloma care. As DRd becomes more common in frontline treatment, there's an urgent need to expand and approve new second-line options to support patients when their disease returns.

 

 

"MIF as a prognostic biomarker in multiple myeloma: clinical significance and in vitro effects"

Source

Dehu Li, Bing Qiao, Qianwen Cheng, Lei Chen, Fei Zhao, Liping Zuo, Qun Li, Chunyan Sun, MIF as a prognostic biomarker in multiple myeloma: clinical significance and in vitro effects, Carcinogenesis, 2025;, bgaf033, https://doi.org/10.1093/carcin/bgaf033 July 9, 2025.  

Overview

This study looked at a protein called macrophage migration inhibitory factor (MIF) and its role in newly diagnosed multiple myeloma (NDMM) patients. MIF is known to play a part in inflammation and cancer, and while it's been studied in other tumors, its role in multiple myeloma hasn’t been well understood—until now.

Researchers found that MIF levels were much higher in the blood of myeloma patients compared to healthy individuals. Patients with high MIF levels also tended to have more advanced disease stages, based on the International Staging System (ISS) and the revised R2-ISS. These patients were more likely to have serious symptoms such as high calcium levels, kidney problems, a large tumor burden, and cancer spreading outside the bone marrow (known as extramedullary disease).

The study also showed that high MIF levels were linked to shorter survival and faster disease progression. In lab experiments, MIF was found to help myeloma cells grow and spread more easily.

In short, this research suggests that MIF could be an important biomarker—a signal doctors can use to better understand a patient's prognosis. Testing for MIF levels may help identify high-risk patients early and guide treatment planning more effectively.

 

 

"Outcomes on peritoneal dialysis in patients with primary kidney disease related to multiple myeloma: A cohort study with data from the French Language Peritoneal Dialysis Registry"

Source

Jolec L, Bechade C, Lanot A, et al. Outcomes on peritoneal dialysis in patients with primary kidney disease related to multiple myeloma: A cohort study with data from the French Language Peritoneal Dialysis Registry. Peritoneal Dialysis International. 2025;0(0). doi:10.1177/08968608251357226  July 9, 2025. 

Overview

This study looked at a protein called macrophage migration inhibitory factor (MIF) and its role in newly diagnosed multiple myeloma (NDMM) patients. MIF is known to play a part in inflammation and c

Kidney problems are common in people with multiple myeloma, and some patients eventually need dialysis to manage chronic kidney disease (CKD). One type of dialysis, called peritoneal dialysis (PD), can offer better quality of life than traditional hemodialysis (HD) because it can be done at home and is less physically demanding. However, PD hasn’t been studied much in people whose kidney disease is caused by myeloma.

This study looked at patients in France who started PD between 2010 and 2020. Out of nearly 13,000 people, 96 had kidney disease related to multiple myeloma (CKD-MM). These patients had more health issues overall and were less likely to be put on the waiting list for a kidney transplant compared to others with different causes of kidney disease.

Even so, the study found that PD worked just as well for CKD-MM patients as it did for others. More than half of the CKD-MM patients passed away during the study period, and 30% eventually switched to HD. Only 5% received a kidney transplant, and this group had a significantly lower chance of receiving a transplant than others.

The results show that PD is a safe and effective dialysis option for myeloma patients with kidney failure, offering similar survival and treatment outcomes as in patients with other types of kidney disease. Improving access to PD and transplant options could help further support this group.

 

 

"Real-World Practice in the Management of Transplant-Eligible Newly Diagnosed Multiple Myeloma: A US-based Cross-Sectional National Survey"

Source

Hossam M. Ali, Zainab Yusufali Motiwala, Yara Shatnawi, Jack Khouri, Faiz Anwer, Hussein Awada, Anam Ashfaque, Danai Dima, Louis S. Williams, Nausheen Ahmed, Al-Ola Abdallah, Leyla O. Shune, Sandra Mazzoni, Muhammad Anns Asif, Maheen Ahmad, Tara Roy, Joslyn Rudoni, Mikhaila Rice, Jonathan Kissam, Diana Basali, Christy J. Samaras, Jason Valent, Beth M. Faiman, Shahzad Raza, Real-World Practice in the Management of Transplant-Eligible Newly Diagnosed Multiple Myeloma: A US-based Cross-Sectional National Survey, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650,https://doi.org/10.1016/j.clml.2025.07.003. July 9, 2025. 

Overview

For patients with newly diagnosed multiple myeloma who are healthy enough for a stem cell transplant (also called transplant-eligible NDMM), treatment usually includes three phases: induction therapy to shrink the cancer, high-dose chemotherapy with transplant, and maintenance therapy to keep the disease under control long term.

This study surveyed U.S. doctors between May and July 2024 to see how treatment choices vary in real-world practice. It looked at how doctors choose treatments based on a patient’s genetic risk, and also how the doctor’s specialty, experience, and type of institution (like academic or community hospital) influence decisions.

The survey found that most doctors now use a four-drug combo—Darzalex® (daratumumab), Velcade® (bortezomib), Revlimid® (lenalidomide), and dexamethasone (Dara-VRd)—as the go-to induction therapy, even in patients with high-risk genetic features. This regimen is often given with weekly subcutaneous bortezomib, lower doses of dexamethasone, and lenalidomide on a 21-day schedule to improve tolerability while still being effective.

After transplant, doctors commonly continue treatment with lenalidomide alone as maintenance therapy. However, the study also found that minimal residual disease (MRD) testing—used to check if any cancer remains after treatment—is still underused.

Overall, the findings show that many doctors are adopting modern, antibody-based four-drug regimens, but there’s still variation in how maintenance therapy is handled and how MRD testing is used. The study highlights the need for more consistent guidelines to help personalize care and improve outcomes for all patients.

 

 

 

"Deletion polymorphisms in the glutathione S-transferase genes are associated with the development of multiple myeloma: a meta-analysis"

Source

Tiongco, R., Mañalac, A., Cayanan, N. et al. Deletion polymorphisms in the glutathione S-transferase genes are associated with the development of multiple myeloma: a meta-analysis. Egypt J Intern Med 37, 100 (2025). https://doi.org/10.1186/s43162-025-00491-0  July 10, 2025. 

Overview

Researchers have been studying certain genes that may affect a person’s risk of developing multiple myeloma. Two of these genes—GSTM1 and GSTT1—are part of a family called glutathione S-transferase (GST), which helps protect cells from damage. Sometimes, people can have missing sections (called deletion polymorphisms) in these genes, and past research has linked these deletions to different types of cancer.

This new study looked at data from four earlier studies, including over 1,100 people, to see if these gene deletions are linked to multiple myeloma. The results showed two different effects: people with a GSTM1 deletion actually had a lower risk of developing myeloma, while those with a GSTT1 deletion had a higher risk.

These findings suggest that changes in GST genes may play a role in determining who develops multiple myeloma, although further research is needed, especially in different populations worldwide, to better understand how these gene deletions influence risk.

 

 

"Maintenance Therapy in the Era of Quadruplets for Multiple Myeloma: When, What, and for How Long?"

Source

H. Mian and L. J. Costa, “ Maintenance Therapy in the Era of Quadruplets for Multiple Myeloma: When, What, and for How Long?,” American Journal of Hematology (2025): 1–3, https://doi.org/10.1002/ajh.70002.  July 10, 2025.  

Overview

In recent years, quadruplet therapy—a combination of four drugs, including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody—has become the standard first treatment for people newly diagnosed with multiple myeloma. These treatments are highly effective, leading to deep and long-lasting responses. Because of this, experts are now questioning whether continuous maintenance therapy—ongoing treatment after the initial response—is still necessary for everyone.

Maintenance therapy became common when early treatments were less powerful. Back then, studies showed that continuing drugs like Revlimid (lenalidomide) after initial therapy helped patients live longer without their disease coming back. But those studies were based on older treatments—often using only two drugs—and may not apply to the newer, more effective quadruplet regimens.

Recent trials show that many patients treated with quadruplet therapy do very well even without indefinite maintenance. For example, in the CASSIOPEIA and PERSEUS trials, patients receiving quadruplets had long periods of remission—often over six years—even without long-term maintenance. And in studies like MASTER, doctors used minimal residual disease (MRD) testing to guide when to stop treatment. Patients who reached deep responses (MRD-negative) were able to safely stop therapy early and still did very well, especially if they didn’t have high-risk genetic features.

On the other hand, continuous maintenance therapy can have downsides. Lenalidomide can cause fatigue, low blood counts, stomach issues, and even increase the risk of new cancers. Long-term use of CD38 antibodies can suppress the immune system, raising the risk of infections and reducing vaccine effectiveness. There's also the financial burden of long-term treatment, which could last 8 to 15 years.

The bottom line is that while maintenance therapy has been a standard part of myeloma care, its role in the era of modern quadruplet treatments is less clear. Some patients may not need treatment forever, especially if they achieve deep, sustained responses. Ongoing studies are exploring how long maintenance therapy should continue and whether stopping it earlier is safe.

For patients, this means a shift toward more personalized treatment plans, with doctors potentially using tools like MRD testing to decide how long maintenance should last, reducing side effects and improving quality of life without sacrificing results.

 

 

"Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma"

Source

Surbhi Sidana, Nausheen Ahmed, Othman Salim Akhtar, Ruta Brazauskas, Temitope Oloyede, Matthew Bye, Doris Hansen, Christopher Ferreri, Ciara L. Freeman, Aimaz Afrough, Larry D. Anderson, Binod Dhakal, Devender Dhanda, Lohith Gowda, Hamza Hashmi, Melanie J. Harrison, Amani Kitali, Heather Landau, Abu-Sayeef Mirza, Pallavi Patwardhan, Muzaffar Qazilbash, Saad Usmani, Krina Patel, Taiga Nishihori, Siddhartha Ganguly, Marcelo C. Pasquini; Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma. Blood 2025; 146 (2): 167–177. doi: https://doi.org/10.1182/blood.2024026216  July 10, 2025.  

Overview

Abecma® (Idecabtagene vicleucel, or ide-cel) is the first CAR-T cell therapy approved by the FDA for treating relapsed or refractory multiple myeloma (R/R MM). While clinical trials showed strong results, those trials only included carefully selected patients. This study looked at how ide-cel performs in the real world, where patients often have more health challenges.

Researchers followed 821 patients who received ide-cel as part of standard care. Most had already been through seven prior treatments and 77% had at least one serious health condition. About one-third were 70 or older, and the group included Black (15%) and Hispanic (7%) patients—groups often underrepresented in trials.

The results were encouraging. The overall response rate was 73%, with 25% of patients achieving a complete response. On average, patients went about 9 months without disease progression. While 80% experienced cytokine release syndrome (CRS)—a known side effect of CAR-T—only 3% had severe cases. Neurological side effects occurred in 28% of patients, with 5% being more serious, but no cases of Parkinsonism were reported.

About 6% of patients died from treatment-related causes, and 45% experienced serious infections. A small number (4%) developed a second cancer, including 1% who developed a type of blood cancer.

Overall, this is the largest real-world study of ide-cel so far, and it shows that the treatment remains effective and generally safe, even for patients who would not have qualified for clinical trials. This gives hope to more people with advanced myeloma who are looking for options after other treatments have stopped working.

 

 

"Real-world data provide a CARbon copy for ide-cel"

Source

Timothy Schmidt; Real-world data provide a CARbon copy for ide-cel. Blood 2025; 146 (2): 131–133. doi: https://doi.org/10.1182/blood.2025029274  July 10, 2025.  

Overview

This commentary highlights a major new real-world study showing that Abecma® (idecabtagene vicleucel, or ide-cel)—the first FDA-approved CAR-T cell therapy for multiple myeloma—works well and is generally safe for patients even outside of clinical trials.

Ide-cel was first approved in 2021 after strong results in the KarMMa trial, where patients with advanced, heavily pretreated myeloma had a 73% response rate and nearly 9 months of progression-free survival. But clinical trials often include only select patients, raising questions about how well these results apply to everyday patients with more complex health issues.

To answer that, a research group analyzed data from over 800 patients treated with ide-cel in real-world clinics across the U.S. The results mirrored those from the original trial, showing similar response rates, survival times, and side effects—even among patients who were older or had other health conditions.

The study also offered important insights into how ide-cel works best:

1. Disease status at the time of infusion matters. Patients who had better control of their myeloma before receiving CAR-T therapy had better long-term results, even if they had received “bridging therapy” (treatment given while waiting for CAR-T cell manufacturing). This suggests that being in a good response before CAR-T may lead to better outcomes.
2. The type of chemotherapy used before CAR-T affects results. The standard drugs used to prepare the body—fludarabine and Cytoxan® (cyclophosphamide) (Flu/Cy)—gave better results than alternatives like bendamustine, which was used more during a fludarabine shortage.
3. Previous treatment with BCMA-targeting drugs can reduce effectiveness. Ide-cel targets the BCMA protein on myeloma cells. If a patient has already received a BCMA-targeting treatment—like another CAR-T, a bispecific antibody, or an antibody-drug conjugate (such as belantamab mafodotin)—ide-cel may not work as well, even if that treatment was given a while ago.

While this study doesn’t answer all the questions—like how ide-cel compares directly to other BCMA-targeted therapies like Carvykti® (cilta-cel), Tecvayli® (teclistamab), or Elrexfio™ (elranatamab)—it confirms that ide-cel is a strong and safe option for many patients, even those who wouldn’t have been eligible for clinical trials. It’s especially effective when used in patients with controlled disease, no prior BCMA therapy, and the right pre-treatment.

In a fast-changing treatment landscape, this kind of real-world data helps doctors and patients make more informed choices about when and how to use CAR-T cell therapy.

 

 

"Characterizing Cellular Expansion of Idecabtagene Vicleucel and Association with Clinical Efficacy and Safety in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma"

Source

Wu, F., Zheng, X., Burnett, J., Masilamani, M., Zhang, W., Zhong, X., Caia, A., Cook, M., Piasecki, J., Kondic, A., Lamba, M. and Zhou, J. (2025), Characterizing Cellular Expansion of Idecabtagene Vicleucel and Association with Clinical Efficacy and Safety in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma. J Clin Pharm. https://doi.org/10.1002/jcph.70075  July 10, 2025.   

Overview

Abecma® (Idecabtagene vicleucel, or ide-cel) is a CAR-T cell therapy designed for people with triple-class-exposed relapsed/refractory multiple myeloma (TCE RRMM. Ide-cel has already shown strong results, helping patients live longer without their disease progressing and increasing overall response rates.

This study looked deeper into how ide-cel behaves inside the body after it’s infused, focusing on how the number of CAR-T cells expands over time and how that expansion relates to both treatment effectiveness and side effects.

Researchers found that the amount of ide-cel a patient received didn’t always predict how much the CAR-T cells would expand in the body. However, when the CAR-T cells expanded more, patients tended to have better outcomes, including longer periods without disease progression and higher response rates. But there was a trade-off: greater cell expansion was also linked to a higher chance of side effects, especially cytokine release syndrome (CRS), which sometimes required treatment with drugs like tocilizumab or steroids.

These results were consistent with earlier findings from the original KarMMa trial, giving doctors more confidence in adjusting the dosing range. Based on this data, the recommended dose range may be safely extended from 300–460 million CAR-T cells to 300–510 million, offering more flexibility in treating patients with TCE RRMM.

In short, this study helps confirm that ide-cel’s effectiveness depends more on how the cells behave inside the body than on the exact starting dose, and that higher cell activity brings both better responses and a need for careful monitoring of side effects.

 

 

"Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma"

Source

Sha Ma, Jieyun Xia, Miao Zhang, Wenyu Li, Meng Xiao, Yuqian Sha, Wenya Wang, Jianteng Zhou, Ying Wang, Kunming Qi, Chunling Fu, Zengtian Sun, Dian Zhou, Qian Sun, Tingting Qiu, Zhiling Yan, Feng Zhu, Wei Chen, Hai Cheng, Wei Sang, Jiang Cao, Depeng Li, Zhenyu Li, Mariateresa Fulciniti, Yao Yao, Kailin Xu, Mingshan Niu; Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma. Blood 2025; 146 (2): 178–190. doi: https://doi.org/10.1182/blood.2024026622  July 10, 2025. 

Overview

GPRC5D is a newer target being used in CAR-T cell therapy for treating multiple myeloma, and early results have shown it can be effective. However, as with many cancer treatments, some patients eventually relapse. This study looked into why that happens by analyzing tissue samples from patients whose myeloma came back after receiving GPRC5D-targeted CAR-T therapy.

Researchers studied the DNA and gene activity from 10 patients. They found that 8 out of 10 patients had lost GPRC5D expression in their myeloma cells. In 3 of these patients, the loss was due to actual genetic damage to the GPRC5D gene or its nearby control areas. Basically, parts of the DNA were missing. But in most other cases, the gene wasn't deleted; it was silenced through a process called DNA methylation, where chemical changes block the gene from being turned on.

The researchers also tested lab-grown myeloma cells and confirmed that when the methylation levels were high, GPRC5D expression was low. Interestingly, when they treated these cells with azacitidine, a drug that reduces DNA methylation, GPRC5D activity came back.

These findings suggest that in many cases, treatment resistance happens not because the gene is gone, but because it's been switched off. Understanding this gives researchers new ideas for how to potentially re-sensitize myeloma cells to CAR-T therapy by using drugs that reverse this gene silencing.

 

 

"Silence of the myeloma clones: GPRC5D epigenetic regulation"

Source

Holly Lee, Nizar J. Bahlis; Silence of the myeloma clones: GPRC5D epigenetic regulation. Blood 2025; 146 (2): 133–135. doi: https://doi.org/10.1182/blood.2025028865  July 10, 2025.  

Overview

This commentary explains important findings from a recent study on GPRC5D-targeted CAR-T therapy, a newer type of treatment for relapsed or refractory multiple myeloma (MM). CAR-T therapies that target GPRC5D—a protein found on myeloma cells—have shown strong results, especially in patients who have already been treated with other therapies like BCMA-targeted drugs. However, most patients eventually relapse, and this research explores why that happens.

The study looked at tumor samples from 10 patients whose myeloma came back after receiving GPRC5D CAR-T therapy. In most of these patients, the myeloma cells had lost GPRC5D expression, meaning the target the CAR-T cells were supposed to find was no longer present. In some cases, this was due to genetic changes, like deletions in the GPRC5D gene or its regulatory regions. But in other patients, the GPRC5D gene wasn’t deleted—it was still there but had been "silenced" by a process called hypermethylation, a chemical change that prevents the gene from being active.

Importantly, the researchers found that in lab tests, a drug called azacitidine, which reduces methylation, was able to turn the GPRC5D gene back on. This raises the possibility of using demethylating agents to restore the effectiveness of GPRC5D-targeted treatments in patients who relapse due to gene silencing—not gene loss.

The study also highlights a key difference between GPRC5D and BCMA, another common CAR-T target. While loss of BCMA is rare, loss or silencing of GPRC5D appears to be much more common after CAR-T therapy. This may be because BCMA is essential for myeloma cells to survive, making it harder for the cancer to get rid of it. GPRC5D, on the other hand, isn’t as critical for myeloma cell survival, so the cells can more easily silence or delete it to escape treatment.

Because of this, scientists are exploring combination therapies that pair GPRC5D-targeted CAR-T with other myeloma treatments. These combinations could help improve immune response, kill cancer cells more effectively, and prevent or delay relapse. Ongoing studies are also looking into whether similar gene-silencing issues affect other CAR-T targets, like BCMA.

In summary, this research shows that relapse after GPRC5D CAR-T therapy is often due to the cancer hiding its target, either by deleting it or turning it off through gene silencing. New strategies—like combining CAR-T with demethylating drugs or other treatments—could help overcome this problem and improve long-term outcomes for patients with multiple myeloma.

 

 

"Boosting CAR T-Cell Efficacy by Blocking Proteasomal Degradation of Membrane Antigens"

Source

Leonie Rieger, Kilian Irlinger, Franziska Füchsl, Marlene Tietje, Anna Purcarea, Nicolas Mathis Barbian, Melanie Faber, Carolin Vogelsang, Lisa Pfeuffer, Sonja Stotz, Oleksandra Karpiuk, Tobias Schulze, Abirami Augsburger, Nadine Glaisner, Verena Konetzki, Sabrina Friedel, Andrej Besse, Lenka Besse, Christoph Driessen, Maike Buchner, Kristina Schwamborn, Katja Steiger, Piero Giansanti, Sebastian Theurich, Johannes M. Waldschmidt, Klaus Martin Kortüm, Michael Hudecek, Hermann Einsele, Marion Högner, Bernhard Kuster, Angela Krackhardt, Judith S. Hecker, Florian Bassermann; Boosting CAR T-Cell Efficacy by Blocking Proteasomal Degradation of Membrane Antigens. Blood 2025; blood.2024027616. doi: https://doi.org/10.1182/blood.2024027616  July 10, 2025. 

Overview

This commentary explains important findings from a recent study on GPRC5D-targeted CAR-T therapy, a newer type of treatment for relapsed or refractory multiple myeloma (MM). CAR-T therapies that target GPRC5D—a protein found on myeloma cells—have shown strong results, especially in patients who have already been treated with other therapies like BCMA-targeted drugs. However, most patients eventually relapse, and this research explores why that happens.

The study looked at tumor samples from 10 patients whose myeloma came back after receiving GPRC5D CAR-T therapy. In most of these patients, the myeloma cells had lost GPRC5D expression, meaning the target the CAR-T cells were supposed to find was no longer present. In some cases, this was due to genetic changes, like deletions in the GPRC5D gene or its regulatory regions. But in other patients, the GPRC5D gene wasn’t deleted—it was still there but had been "silenced" by a process called hypermethylation, a chemical change that prevents the gene from being active.

Importantly, the researchers found that in lab tests, a drug called azacitidine, which reduces methylation, was able to turn the GPRC5D gene back on. This raises the possibility of using demethylating agents to restore the effectiveness of GPRC5D-targeted treatments in patients who relapse due to gene silencing—not gene loss.

The study also highlights a key difference between GPRC5D and BCMA, another common CAR-T target. While loss of BCMA is rare, loss or silencing of GPRC5D appears to be much more common after CAR-T therapy. This may be because BCMA is essential for myeloma cells to survive, making it harder for the cancer to get rid of it. GPRC5D, on the other hand, isn’t as critical for myeloma cell survival, so the cells can more easily silence or delete it to escape treatment.

Because of this, scientists are exploring combination therapies that pair GPRC5D-targeted CAR-T with other myeloma treatments. These combinations could help improve immune response, kill cancer cells more effectively, and prevent or delay relapse. Ongoing studies are also looking into whether similar gene-silencing issues affect other CAR-T targets, like BCMA.

In summary, this research shows that relapse after GPRC5D CAR-T therapy is often due to the cancer hiding its target, either by deleting it or turning it off through gene silencing. New strategies—like combining CAR-T with demethylating drugs or other treatments—could help overcome this problem and improve long-term outcomes for patients with multiple myeloma.

 

 

"A Multi-stakeholder Qualitative Analysis of Barriers to Autologous Stem Cell Transplantation for Multiple Myeloma"

Source

James Fan Wu, Idayat M. Akinola, Anita D’Souza, Rachel Cusatis, A Multi-stakeholder Qualitative Analysis of Barriers to Autologous Stem Cell Transplantation for Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.07.002. July 11, 2025. 

Overview

This study looked at why some people with multiple myeloma (MM) have trouble getting autologous stem cell transplants (ASCT). Researchers interviewed patients, transplant doctors, and referring doctors across Wisconsin to understand the challenges from all sides.

They found four main barriers: lack of caregiver support, patient concerns and understanding, financial stress, and logistical issues like travel and scheduling. Patients without nearby family or close friends—especially those who are single, childless, or live in rural areas—often struggled most with finding someone to help them during recovery. Many patients also worried about side effects, long hospital stays, and how treatment might affect their quality of life.

While patients often searched the internet and joined support groups to learn more, discussions about costs were rare, even though nearly all patients felt financial pressure. Getting to a transplant center was another big hurdle, especially for people living far away or needing help with transportation and coordinating care.

Another key issue was that some patients were never referred to a transplant center in the first place—especially those treated in smaller community clinics. These patients may face the biggest barriers and never even get the chance to consider ASCT.

Overall, this study gives important insight into the real-world obstacles patients and doctors face when it comes to stem cell transplants. To make sure more people can benefit from ASCT, new strategies are needed to improve support systems, patient education, affordability, and referral processes.

 

 

"Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics"

Source

Raymond K.H. Yip, Jeremy Er, Lei Qin, Quoc Hoang Nguyen, Allan Motyer, Joel S Rimes, Amanda Light, Ruvimbo D Mishi, Ling Ling, Casey J.A. Anttila, Ellen Tsui, Daniela Amann-Zalcenstein, Mark R Dowling, Kelly L. Rogers, Rory Bowden, Yunshun Chen, Simon J Harrison, Edwin D Hawkins; Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics. Blood 2025; blood.2025028896. doi: https://doi.org/10.1182/blood.2025028896  July 11, 2025.  

Overview

Researchers are learning that the bone marrow environment plays a major role in how multiple myeloma starts and grows. But until now, the specific details of how this environment works—especially how it supports cancerous plasma cells—haven’t been well understood.

In this study, scientists used a cutting-edge technique called spatial transcriptomics to look at the activity of over 5,000 genes directly within bone marrow samples. They studied tissue from 21 people, including those with healthy bone marrow, pre-myeloma conditions, and newly diagnosed multiple myeloma.

By combining this technology with a special method for preserving bone marrow tissue, the team was able to clearly identify different types of cells—including normal and cancerous plasma cells—and where they were located in the bone marrow. They found that in many cases, myeloma cells clustered into distinct areas, and the surrounding environment in those areas was quite different from one patient to another—even within the same bone marrow sample.

These findings suggest that there’s no single “one-size-fits-all” bone marrow environment that supports myeloma growth. Instead, different subgroups of myeloma cells may create their own unique environments, which can vary widely across patients and even within a single patient.

Understanding these differences could help doctors develop more targeted and personalized treatments, based on the specific environment surrounding the cancer in each person’s bone marrow.

 

 

"Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma"

Source

Tim Richardson, Udo Holtick, Jan Hendrik Frenking, Hishan Tharmaseelan, Hyatt Balke-Want, Ruth Flümann, Elias K Mai, Sandra Sauer, Raphael Teipel, Malte von Bonin, Michael Hallek, Christoph Scheid, Philipp Gödel; Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma. Blood Adv 2025; bloodadvances.2025016712. doi: https://doi.org/10.1182/bloodadvances.2025016712  July 11, 2025.   

Overview

Treating multiple myeloma after it returns following BCMA-targeted CAR-T cell therapy remains a big challenge. This study looked at whether it’s possible—and safe—to give a second CAR-T therapy targeting the same protein, BCMA, using a different product.

Researchers followed 10 patients who had already received idecabtagene vicleucel (ide-cel) and later relapsed. These patients were then treated with a second CAR-T therapy called Carvykti® (ciltacabtagene autoleucel, or cilta-cel). Some patients received other treatments between the two CAR-T infusions to help control their disease.

The results were promising. The second round of CAR-T therapy was safe, with no unexpected or serious immune side effects. All patients had a strong response—100% achieved a very good partial response (VGPR) or better, and 60% reached minimal residual disease (MRD) negativity, meaning no signs of myeloma were detectable. At 6 months, nearly 65% were still in remission.

The study also found that patients who responded well to the first CAR-T treatment were more likely to have longer-lasting responses to the second. Only one patient lost the BCMA target on their myeloma cells after the second CAR-T, which can make treatment less effective. Unfortunately, two of the three patients who relapsed again after the second CAR-T passed away within a year and didn’t respond to follow-up treatments with bispecific antibodies.

This early real-world data suggests that sequential treatment with two different BCMA CAR-T therapies is both possible and effective, especially for patients who responded well to their first CAR-T therapy.

 

 

"Cognitive Performance in Patients with Multiple Myeloma Treated with an Autologous Stem Cell Transplant: Results of the Brilliant Study"

Source

Cesar Rodriguez, Melanie Tam, David Hurd, Emily V. Dressler, Sarada Krishnamurthy, Rakhee Vaidya, Sydney Smith, Stephen R. Rapp, Michelle L. Wallander, Katie E. Duckworth, Cognitive Performance in Patients with Multiple Myeloma Treated with an Autologous Stem Cell Transplant: Results of the Brilliant Study, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.07.004.  July 11, 2025. 

Overview

This study looked at how autologous stem cell transplant (ASCT) affects cognitive function in people with newly diagnosed multiple myeloma. While we know ASCT is an important part of treatment after chemotherapy, it's not clear whether it affects how patients think, remember, or process information.

Researchers followed 38 patients through their transplant journey. They used two types of cognitive tests: one that patients could do themselves (SAGE) and one that was given by a trained provider (MoCA). Patients took these tests before the transplant, 100 days after, and again one year later.

The results showed no signs of cognitive decline after transplant. In fact, the scores slightly improved over time, though the changes weren’t statistically significant. Patients had no strong preference between doing the tests themselves or having a provider administer them.

Overall, this study suggests that ASCT does not appear to harm cognitive function. Testing brain function during and after treatment is both doable and well-received by patients. This helps reassure patients and providers that memory and thinking abilities are likely to remain stable through this part of multiple myeloma treatment.

 

 

"Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma"

Source

Grigoris Georgiou, George Minadakis, Nestoras Karathanasis, Kyriaki Savva, Efi Athieniti, Marilena M Bourdakou, George M Spyrou, Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma, Computational and Structural Biotechnology Journal, 2025, ISSN 2001-0370, https://doi.org/10.1016/j.csbj.2025.07.017. July 12, 2025. 

Overview

Researchers are working to better understand how multiple myeloma (MM) progresses by studying how genes behave at different stages of the disease. MM is a type of blood cancer where abnormal plasma cells build up in the bone marrow and produce too much of one type of antibody, which can damage organs over time.

In this study, scientists used a computer-based approach to look at gene activity in patients with MM, based on how advanced their disease was. They focused on three kinds of gene behavior: genes that change a lot between stages (called differentially expressed genes), genes that increase or decrease steadily across stages (monotonically expressed genes), and pairs of genes that change in a predictable ratio as MM progresses.

By studying these gene patterns, the team was able to identify small groups of key genes that may help doctors tell what stage a patient's MM is in. These genes were also linked to important biological processes like how cells grow and divide. This could help scientists better understand what drives MM and possibly lead to new tools for tracking or treating the disease more precisely in the future.

This study developed a new way to find and analyze gene patterns in MM that could help improve how the disease is monitored and understood.

 

 

"B4GALT3 as a Key Glycosyltransferase Gene in Multiple Myeloma Progression: Insights From Bioinformatics, Machine Learning, and Experimental Validation"

Source

Yang, A., Ke, M., Feng, L., Yang, Y., Chen, J. and Zeng, Z. (2025), B4GALT3 as a Key Glycosyltransferase Gene in Multiple Myeloma Progression: Insights From Bioinformatics, Machine Learning, and Experimental Validation. Molecular Carcinogenesis. https://doi.org/10.1002/mc.70013 July 13, 2025. 

Overview

Researchers are learning more about how certain sugar-related processes in cells—called glycosylation—may affect the growth and survival of multiple myeloma (MM). Glycosylation is important in many types of cancer, but its role in MM hasn't been well understood. This study focused on a group of genes called glycosyltransferases (GTs) that control glycosylation, to see if they could help predict how MM develops and progresses.

Using data from large MM patient databases, the researchers built a glycosyltransferase-related prognostic model (GTPM). This model used machine learning to sort patients into high-risk and low-risk groups. People in the low-risk group lived significantly longer. The model also outperformed other well-known tools used to predict MM survival.

One gene in particular, called B4GALT3, stood out. It was found at higher levels in patients with more advanced MM and was linked to shorter survival times. Lab tests showed that when B4GALT3 was reduced in MM cells, the cancer cells slowed down, stopped spreading as much, and were more likely to die. The study also uncovered how B4GALT3 works—by affecting cell stress in the endoplasmic reticulum and by altering a key cancer pathway known as Wnt/β-catenin.

This research offers a new way to predict MM outcomes and identifies B4GALT3 as a promising target for future treatments.

 

 

"Inhibition of FOXM1 Synergizes with BH3 Mimetics Venetoclax and Sonrotoclax in Killing Multiple Myeloma Cells through Repressing MYC Pathway"

Source

Z. Wen, Y. Wang, K. C. Fox, A. M. Bissonnette, L. F. Moat, T. E. Kitchner, K. Springstroh, S. H. Kim, D. S. Sheerar, P. Tanawattanacharoen, C. A. Leon, S. O. Fagbemi, J. A. Katzenellenbogen, S. J. Hebbring, B. S. Katzenellenbogen, S. Janz, A. A. Onitilo, Inhibition of FOXM1 Synergizes with BH3 Mimetics Venetoclax and Sonrotoclax in Killing Multiple Myeloma Cells through Repressing MYC Pathway. Adv. Sci. 2025, e08822. https://doi.org/10.1002/advs.202508822  July 14, 2025.  

Overview

Relapsed and refractory multiple myeloma (RRMM) continues to be the main cause of death from multiple myeloma, and finding better treatment options is critical. One protein, called FOXM1, is known to play a major role in RRMM, making it an important target for new therapies.

In this study, researchers tested several FDA-approved drugs to see which ones could work well with a FOXM1-blocking drug called NB73. They found that Venetoclax, a drug already used in some myeloma cases, worked especially well when combined with NB73. This combination effectively killed myeloma cells in both lab models and animal studies without causing serious side effects.

NB73 works by tagging FOXM1 so it can be broken down by the cell. Venetoclax makes this process even stronger. Together, they also stop FOXM1 from turning on other cancer-related genes like PLK1, which is involved in cell growth. Blocking PLK1 directly with another drug (GSK461364) also worked well when paired with NB73.

Interestingly, in one myeloma cell line that didn’t respond to Venetoclax, adding newer drugs like Sonrotoclax and Ceritinib helped restore sensitivity to treatment.

These results show that targeting FOXM1 could make existing drugs like Venetoclax more effective for people with RRMM. The findings may also help explain why some past trials, like the Phase III CANOVA study, didn’t meet expectations, possibly because they didn’t account for the role of FOXM.

 

 

"Label-free protein-structure-sensitive live-cell microscopy for patient-specific assessment of myeloma therapy"

Source

Gasparin, F., Tietje, M.R., Katab, E. et al. Label-free protein-structure-sensitive live-cell microscopy for patient-specific assessment of myeloma therapy. Nat. Biomed. Eng (2025). https://doi.org/10.1038/s41551-025-01443-3 July 14, 2025. 

Overview

Current tests to check how well treatment is working in multiple myeloma often rely on looking at large numbers of cells or blood samples to measure certain proteins. These methods, like flow cytometry and blood tests for light chains or monoclonal antibodies, are useful but time-consuming and only provide information about the overall tumor, not individual cells.

This new study introduces a more advanced and efficient approach. Researchers developed a single-cell imaging technique that needs far fewer cells and can track how individual myeloma cells respond to treatment over time. The method uses mid-infrared optoacoustic microscopy, a technology that captures sound waves generated by light absorbed in the cell. This lets scientists “see” how proteins are changing inside living cells, without needing labels or dyes.

A key feature of the technique is its ability to detect intermolecular β-sheets, a type of protein structure that helps signal whether a cell is alive or dying. This structure becomes more noticeable when proteasome inhibitors—common drugs used in myeloma treatment—start working.

Overall, this technology offers a powerful new way to track how well treatments are working in real time, even at the single-cell level. It could help doctors better understand which patients are responding to therapy and tailor treatment more precisely.

 

 

"Solitary but not simple─a call for precision risk stratification and individualized treatment in solitary plasmacytoma"

Source

Zanwar, S., Rajkumar, S.V. Solitary but not simple─a call for precision risk stratification and individualized treatment in solitary plasmacytoma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02701-8 July 14, 2025. 

Overview

Solitary plasmacytoma is a rare condition where a single mass of abnormal plasma cells forms, either in bone or soft tissue, without signs of full-blown multiple myeloma. Doctors confirm this diagnosis by ruling out systemic disease through blood tests, scans, and bone marrow evaluation. But not all solitary lesions are the same. Some patients have no plasma cells in the bone marrow, while others may have a small number. When 10% or more of the marrow is involved, it’s classified as multiple myeloma. These differences matter because they affect how the disease progresses and how it's treated.

Traditionally, patients with solitary plasmacytoma have been treated with localized radiation or surgery. Many stay in remission, but some eventually relapse or progress to multiple myeloma, sometimes unpredictably. One of the biggest challenges is figuring out which patients are at higher risk of this happening. While there's some evidence that adding systemic therapy (treatment that affects the whole body) may help in borderline cases, there are no large clinical trials to guide doctors on when or how to use it.

A recent study by Burroni and colleagues sheds new light on this issue. They analyzed tumor samples from 47 patients with solitary bone plasmacytoma using advanced genetic tests. They found that the disease is more complex at the genetic level than previously thought. About 60% of patients had mutations in the MAPK pathway—a group of genes involved in cell growth. One gene in particular, KRAS, stood out. Patients with KRAS mutations were more likely to progress quickly to multiple myeloma. The same was true for mutations in TP53 and other genes related to DNA repair. When both KRAS and TP53 mutations were present, the outcomes were especially poor. On the flip side, patients without these high-risk genetic changes had a much better chance of remaining progression-free for at least five years.

While the study has some limitations—it didn’t clearly separate patients with minimal bone marrow involvement from those without any—it shows that genetic testing could help doctors better predict outcomes and tailor treatment. It also highlights the importance of follow-up care, especially for patients with high-risk features. Ultimately, more research is needed, but these findings could help shape future treatment strategies and improve care for patients with solitary plasmacytoma.

 

 

"Neurologic Adverse Events Associated With T-cell Engager Therapy in Multiple Myeloma: A Pharmacovigilance Study"

Source

Khan M, Khan F, Irfan S, et al. (July 14, 2025) Neurologic Adverse Events Associated With T-cell Engager Therapy in Multiple Myeloma: A Pharmacovigilance Study. Cureus 17(7): e87950. doi:10.7759/cureus.87950  July 14, 2025.  

Overview

T-cell engager (TCE) therapies like teclistamab, talquetamab, and elranatamab are promising treatments for relapsed or refractory multiple myeloma (RRMM). But these newer drugs can also cause serious side effects—especially ones that affect the brain and nervous system. This study looked at how often these neurological side effects (called NAEs) were reported for each of the three drugs and compared their overall safety profiles.

Out of nearly 2,000 reports of side effects in the FDA's 2024 database, over a quarter involved the nervous system. Teclistamab had the highest total number of side effect reports, including the most neurological ones, followed by talquetamab and then elranatamab. However, when researchers looked at the proportion of neurological effects compared to total side effects, talquetamab showed the highest relative risk. Elranatamab had the lowest.

One serious complication across all three drugs was ICANS (immune effector cell–associated neurotoxicity syndrome), a potentially dangerous condition. It was most commonly reported with teclistamab and elranatamab, and less so with talquetamab. The study also found other neurological problems like peripheral neuropathy and nerve damage, especially with elranatamab. Interestingly, taste disorders were common with talquetamab, possibly because it targets a specific receptor (GPRC5D) also found on the tongue.

Teclistamab, the first of the three to be approved by the FDA, had more widespread use, which might explain its higher number of side effect reports. Still, the data suggest it may carry a higher risk of neurotoxicity, especially in people with pre-existing nerve or brain issues. The findings also emphasize the need for doctors to watch for early signs of neurological problems and act quickly with treatments like steroids or dose changes if needed.

While this study provides helpful real-world insights, it has limitations. Reports to the FDA system are voluntary, which means some side effects might be underreported or missing important details. Even so, the data help us understand how these therapies are working outside of clinical trials and underline the importance of careful monitoring and further research.

In short, while TCE therapies are effective for RRMM, they can cause neurological side effects, especially ICANS with teclistamab and taste issues with talquetamab. Patients and doctors should stay alert to symptoms and work together to manage side effects without giving up effective treatment.

 

 

"Analysis of remobilization efficiency of etoposide combined with cytarabine and pegfilgrastim, with or without plerixafor, for multiple myeloma recurrence following autologous hematopoietic stem cell transplantation"

Source

Zhou, Y., Qian, H., Zheng, J. et al. Analysis of remobilization efficiency of etoposide combined with cytarabine and pegfilgrastim, with or without plerixafor, for multiple myeloma recurrence following autologous hematopoietic stem cell transplantation. Clin Exp Med 25, 247 (2025). https://doi.org/10.1007/s10238-025-01784-y July 14, 2025. 

Overview

For patients with multiple myeloma (MM) who relapse after initial treatment, a second stem cell transplant (called salvage ASCT) is often recommended, especially if the first remission lasted more than 18 months. However, collecting enough healthy stem cells for this second transplant can be difficult. Factors like age, previous chemotherapy, and weakened bone marrow can all reduce the number of stem cells available.

Traditionally, drugs like Cytoxan® (cyclophosphamide), cytarabine, or etoposide have been used to help release (mobilize) stem cells into the blood. But these regimens often cause serious side effects such as low white blood cell and platelet counts, infections, and even rare deaths. Another option, plerixafor, can boost stem cell collection and is less toxic, but it's expensive and not widely available.

To improve results, researchers studied a combination of etoposide, cytarabine, and pegfilgrastim, known as the EAP regimen, either alone or with plerixafor. They tested this approach on 11 patients across three medical centers in China, all of whom had relapsed more than 18 months after their first ASCT. The results were promising: all 11 patients successfully collected enough stem cells for another transplant. Nearly half used plerixafor and still achieved a 100% success rate. On average, collection was completed in just under two days.

While some patients experienced temporary drops in blood counts or moderate infections, there were no severe complications, bleeding events, or treatment-related deaths. Most patients went on to receive a second ASCT, with good recovery of both white blood cells and platelets afterward.

In short, this study suggests that the EAP regimen—with or without plerixafor—is a safe and effective option for collecting stem cells in relapsed MM patients. It works well even in people who’ve had previous transplants, shortens the number of collection days, and has manageable side effects. Larger studies are needed, but these findings point to a practical and potentially lifesaving option for patients preparing for a second ASCT.

 

 

"Utilizing genomics to identify novel immunotherapeutic targets in multiple myeloma high-risk subgroups"

Source

Liu, E., Jaouadi, O., Sharma, R. et al. Utilizing genomics to identify novel immunotherapeutic targets in multiple myeloma high-risk subgroups. Genome Med 17, 79 (2025). https://doi.org/10.1186/s13073-025-01503-y  July 15, 2025. 

Overview

Immunotherapy is a key part of treatment for multiple myeloma, with most therapies targeting proteins like BCMA, CD38, and GPRC5D found on myeloma cells. But because myeloma is a highly variable disease—both between patients and within the same patient—new and more specific targets are needed to improve how well these therapies work.

In this study, researchers analyzed large datasets using a method called “multi-omics,” which looks at different layers of biological information, including gene expression and cell surface markers. Their goal was to discover new proteins on the surface of myeloma cells that could be used as future immunotherapy targets. They focused on proteins that are present on cancer cells but not on most healthy tissues to reduce the risk of side effects.

The researchers found several promising new targets. Some of these, like ITGA4 and LAX1, were common across many patients. Others were linked to specific genetic subtypes of myeloma. For example, they found CD20 in patients with the t(11;14) subtype, and GPRC5D in cases with 1q gain. They confirmed that these proteins were actually present on myeloma cells using lab techniques like flow cytometry and gene editing.

Importantly, they also discovered that even within a single patient, different subgroups of cancer cells might show different target proteins. This helps explain why some patients stop responding to certain treatments—if the protein being targeted disappears or changes, the treatment becomes less effective. One way this can happen is through a process called “alternative splicing,” where the cancer cells change how a protein is made so it no longer looks the same to the immune system.

Overall, this research lays out a new, systematic way to find better and more personalized targets for myeloma immunotherapy. It could lead to improved treatment strategies, especially for patients whose disease no longer responds to current options.

 

 

"Comprehensive analysis of exosome-related gene signature in multiple myeloma prognosis and immune microenvironment evaluation"

Source

Zheng, D., Zhang, B., Wang, Q. et al. Comprehensive analysis of exosome-related gene signature in multiple myeloma prognosis and immune microenvironment evaluation. Cancer Immunol Immunother 74, 269 (2025). https://doi.org/10.1007/s00262-025-04097-x July 15, 2025. 

Overview

Researchers are always looking for better ways to predict how multiple myeloma (MM) will progress in different patients. A new study has focused on tiny particles called exosomes, which are released by tumor cells. These exosomes help cancer grow by affecting the immune system and surrounding tissue. While exosomes are known to play a role in cancer, their impact on myeloma hadn’t been fully explored—until now.

In this study, scientists looked at genes related to exosomes, called exosome-related genes (ERGs), to create a new tool that helps predict survival in people with myeloma. They analyzed patient data from two large databases and found six ERGs that were linked to patient outcomes. These genes—BIRC5, LDHA, MRPS30, MRPL15, RPL26L1, and S1PR2—were used to build a risk score. Patients with higher scores were more likely to have aggressive disease and lower survival rates.

This new model was able to predict 3-year survival with fairly high accuracy and worked well when tested on different patient groups. When combined with other important factors like age and stage of disease, it provided even more accurate predictions.

The researchers also found that patients in the high-risk group had changes in their immune systems. Specifically, they had fewer immune cells that help fight cancer and signs of being less likely to respond to immunotherapy. These findings were confirmed using lab experiments and data from other cancer research projects.

Overall, this study introduces a new, more precise way to assess risk in myeloma patients by focusing on exosome-related genes. This could help doctors personalize treatment plans based on how aggressive the disease is likely to be.

 

 

"Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial"

Source

Vania Hungria, Paweł Robak, Marek Hus, Vera Zherebtsova, Christopher Ward, P Joy Ho, Roman Hájek, Kihyun Kim, Sebastian Grosicki, Hanlon Sia, Adam Bryant, Marcelo Pitombeira de Lacerda, Gracia Aparecida Martinez, Anna Sureda Balarí, Irwindeep Sandhu, Claudio Cerchione, Peter Ganly, Meletios A Dimopoulos, Chengcheng Fu, Mamta Garg, Al-Ola Abdallah, Moshe E Gatt, Albert Oriol Rocafiguera, Michele Cavo, Robert Rifkin, Tomoaki Fujisaki, Michał Mielnik, Joseph Ficek, Alejandro Mantero, Nick Pirooz, Sybil Varghese, Joe Lee, Astrid McKeown, Rachel Rogers, Hena Baig, Lydia Eccersley, Sumita Roy-Ghanta, Pralay Mukhopadhyay, Jacqueline Nielsen, Joanna Opalinska, María-Victoria Mateos, Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial, The Lancet Oncology, 2025, ISSN 1470-2045, https://doi.org/10.1016/S1470-2045(25)00330-4. July 15, 2025. 

Overview

A major clinical trial called DREAMM-7 has shown promising results for a new treatment combination for people with relapsed or refractory multiple myeloma (RRMM). In this study, researchers compared two treatment options: one combining Blenrep® (belantamab mafodotin), Velcade® (bortezomib), and dexamethasone (BVd) and the other using Darzalex® (daratumumab), bortezomib, and dexamethasone (DVd). Both treatments were tested in patients who had already received at least one prior therapy for multiple myeloma.

The updated results from the trial, which included nearly 500 patients from around the world, showed that patients who received BVd lived significantly longer than those who received DVd. At the time of this follow-up, the median overall survival for the BVd group hadn’t even been reached, which means many patients were still alive. This is a strong sign of the treatment’s effectiveness.

BVd also helped more patients reach deep remissions. In fact, twice as many patients on BVd had no measurable signs of disease at a molecular level compared to those on DVd. The duration of response was also much longer in the BVd group, which was over 40 months compared to under 18 months with DVd.

The treatment was generally well-tolerated, though side effects were more common with BVd. These included low platelet counts and infections like pneumonia. Still, most of these side effects were manageable. A small number of patients in both groups experienced serious side effects that led to death, though this was slightly higher in the BVd group.

Overall, the results suggest that BVd may offer a more effective option for patients with RRMM and could become a new standard of care. It provided better survival outcomes, longer-lasting responses, and deeper remissions compared to DVd.

 

 

"Patient-reported outcomes with belantamab mafodotin, bortezomib, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): results from a phase 3, open-label, randomised controlled trial"

Source

Vania Hungria, Marek Hus, ChengCheng Fu, Vera Zherebtsova, Christopher Ward, P Joy Ho, Damian Mikulski, Ludmila Muronova, Claudio Cerchione, Angely Loubert, Laurine Bunod, Manal M'Hari, Nick Pirooz, Rachel Rogers, Chee Paul Lin, Sumita Roy-Ghanta, Joanna B Opalinska, Molly Purser, Astrid McKeown, Simon McNamara, Hena Baig, Lydia Eccersley, Farrah Pompilus, María-Victoria Mateos, Abhinav Chandra, Adam Bryant, Albert Oriol, Alberto Velasco Valdazo, Alessandra Larocca, Alessandro Rambaldi, Al-Ola Abdallah, Ana Carolina Ribas de Almeida, Andrew Lim, Andrew Spencer, Angelo Maiolino, Angelo Belotti, Anna Maria Sureda, Anupkumar George, Aristeidis Chaidos, Baijun Fang, Bing Chen, Bradley Augustson, Bulat Bakirov, Caressa Meert, Carmen Martinez Chamorro, Carolina Villarim, Ceri Bygrave, Chai Phua, Chang Ki Min, Chengcheng Fu, Christopher Ward, Claudia Cellini, Claudio Cerchione, Cristina Encinas Rodríguez, Dominik Dytfeld, Eirini Katodritou, Esther González García, Felipe De Arriba de la Fuente, Francesco Di Raimondo, Gang An, Gordon Marron, Gracia Aparecida Martinez, Habte Yimer, Hanlon Sia, Henri Schots, Ho-Jin Shin, Ignacio Casas Avilés, Igor Davydkin, Ioannis Kotsianidis, Irit Avivi, Irwindeep Sandhu, Ivan Moiseev, Ivan Spicka, Jae-Cheol Jo, James Essell, Jean-Samuel Boudreault, Jie Jin, Joanna Romejko-Jarosinska, Ka Chun Cheung, Kamaraj Karunanithi, Kevin Boyd, Kihyun Kim, Krzysztof Giannopoulos, Laura Maria Fogliatto, Laurent Garderet, Ludek Pour, Mamta Garg, Marcelo Pitombeira de Lacerda, Marek Hus, Margaret Macro, María Victoria Mateos, Marie-Christiane Vekemans, Mark-David Levin, Martin Kortuem, Meletios A. Dimopoulos, Mercedes Gironella, Merit Hanna, Michele Cavo, Michihiro Uchiyama, Miriam Kull, Monica Bocchia, Moshe Gatt, Nicholas Weber, Olaposi Yomade, Olga Samoilova, Olivier Decaux, P Joy Ho, Paolo Corradini, Paul Cannell, Paula Rodriguez Otero, Pawel Robak, Peter Presgrave, Peter Ganly, Rachel Hall, Robert Rifkin, Roland Fenk, Roman Hajek, Sebastian Theurich, Sebastian Grosicki, Sergey Voloshin, Soo-Mee Bang, Stephen Ting, Sujun Gao, Szymon Fornagiel, Tatyana Shelekhova, Tomoaki Fujisaki, Udo Holtick, Valerio De Stefano, Vania Hungria, Vera Zherebtsova, Vladimir Maisnar, Wenming Chen, Wilfried W.H. Roeloffzen, Wojciech Jurczak, Wojciech Janowski, Yulia Dyachkova, Zhen Cai, Zhongjun Xia, Patient-reported outcomes with belantamab mafodotin, bortezomib, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): results from a phase 3, open-label, randomised controlled trial, The Lancet Haematology, 2025, ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(25)00163-2. July 15, 2025. 

Overview

A new analysis from the DREAMM-7 clinical trial looked at how patients with relapsed or refractory multiple myeloma (RRMM) felt during treatment with two different drug combinations. Both groups received Velcade® (bortezomib) and dexamethasone, but one group also got Blenrep® (belantamab mafodotin), while the other received Darzalex® (daratumumab). The goal was to see how each treatment affected patients’ quality of life—how they felt physically and emotionally during their care.

The results showed that most patients in both groups maintained or even improved their overall quality of life during treatment. This included feeling better in areas like general health, physical function, daily activities, and symptoms related to their disease. Patients also reported that side effects were manageable, with the majority saying they were “not at all,” “a little,” or only “somewhat” bothered by them.

Importantly, the study found that people receiving belantamab mafodotin had a similar or better experience with their treatment compared to those on  daratumumab, adding to earlier findings that belantamab also helps patients live longer without disease progression. These results support the growing case for belantamab mafodotin as a strong treatment option for patients with RRMM. 

 

 

"Selinexor-loaded polymeric micelle for multiple myeloma therapy, Chinese Chemical Letters"

Source

Peipei Yang, Ying Qu, Bingyang Chu, Wen Chen, Xue Wei, Meng Pan, Mengyao Wang, Yun Yang, Qingya Liu, Yuhuan Zheng, Ting Niu, Zhiyong Qian, Selinexor-loaded polymeric micelle for multiple myeloma therapy, Chinese Chemical Letters, 2025, 111586, ISSN 1001-8417, https://doi.org/10.1016/j.cclet.2025.111586. July 15, 2025. 

Overview

Researchers are working on a new way to deliver the multiple myeloma drug selinexor to make it safer and more effective. Xpovio® (selinexor) is already approved for relapsed or hard-to-treat myeloma and has shown it can help patients live longer. However, it often causes serious side effects—especially stomach-related issues—that can limit how much patients can take and how well they tolerate treatment.

To solve this, scientists created a micelle-based nanoformulation—a tiny, controlled-release delivery system made from special materials (called mPEG-PCL). This system wraps around selinexor to help the drug work better while reducing harm to the body. In lab studies and in mice with myeloma, the new micelle version of selinexor showed strong cancer-fighting effects at lower doses and helped the animals live longer than those given regular selinexor.

Just as important, this new version caused fewer side effects, especially in the stomach and intestines. It helped protect the gut lining and supported a healthier mix of gut bacteria. This improved tolerability could help more patients stay on treatment and get better results.

This new formulation of selinexor may offer a safer, more effective way to treat multiple myeloma, especially for those who struggle with side effects from the standard drug.

 

 

"Lymphocyte Kinetics and Outcomes of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma With Out of Specification Products"

Source

S. Dingli, P. Rothweiler, M. Binder, et al., “ Lymphocyte Kinetics and Outcomes of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma With Out of Specification Products,” American Journal of Hematology (2025): 1–4, https://doi.org/10.1002/ajh.70001. July 15, 2025

Overview

CAR-T cell therapy has become an exciting treatment option for patients with relapsed or refractory multiple myeloma. Unlike most other treatments, CAR-T requires collecting a patient's own immune cells and sending them to a lab, where they're modified and grown over several weeks. While the process is carefully controlled, sometimes the final CAR-T product doesn’t meet all the quality requirements set by the FDA. These products are called "out-of-specification" (OOS), and they may vary in dose, cell quality, or activity. Still, in many cases, patients and doctors choose to go ahead with these treatments because other options are limited.

In this study, doctors looked at how patients responded to OOS CAR-T therapy using Carvykti® (cilta-cel) and compared the results with those who received the “in-spec” version. Out of 73 patients who got cilta-cel at their center, 22 (about 30%) received an OOS product. The groups had similar disease characteristics, including age, prior treatments, and disease risk level.

Side effects like cytokine release syndrome (CRS) and neurotoxicity (ICANS) were seen in both groups, with a slightly lower rate of CRS and a higher—but shorter-lasting—rate of ICANS in the OOS group. Early on, the immune system took longer to recover in the OOS group, but by day 15 after CAR-T treatment, recovery was similar between the two groups.

Importantly, the response to treatment was strong in both groups. At three months, most patients had a very good partial response (VGPR) or better, with no significant difference in outcomes. While some early signs suggested fewer minimal residual disease (MRD) negative results in the OOS group, this gap closed by month three. After about 1.5 years of follow-up, there was no meaningful difference in how long patients lived or how long they stayed in remission.

The study suggests that even if a cilta-cel product doesn’t meet all FDA specifications, patients may still respond just as well as those who receive an in-spec version. Although the number of patients in this study was small, the findings offer reassurance for patients and doctors facing tough decisions. As CAR-T therapy moves into earlier stages of treatment, the frequency of OOS products may go down—but when they do occur, this data shows they can still be effective and safe.

 

 

"Construction of a machine learning-based screening model for IgD myeloma"

Source

Manli Zhou, Sisi Feng, Construction of a machine learning-based screening model for IgD myeloma, Clinica Chimica Acta, 2025, 120488, ISSN 0009-8981, https://doi.org/10.1016/j.cca.2025.120488. July 15, 2025. 

Overview

Immunoglobulin D (IgD) myeloma is a rare form of multiple myeloma, making up only about 1–2% of all cases. Because IgD levels in the blood are very low, this subtype is easy to miss during routine tests, which can lead to delayed or missed diagnosis.

To help solve this problem, researchers used machine learning to develop a tool that could identify IgD myeloma using common blood tests and lab results. They studied data from 83 patients with IgD myeloma and 166 patients with other types of myeloma. Several machine learning methods were tested, and the best results came from a model called random forest.

This model used seven key features—LDH, albumin, creatinine, calcium, β2 microglobulin, age, and hemoglobin—to spot patterns linked to IgD myeloma. It performed very well, with an accuracy rate of over 95% in identifying patients with IgD myeloma. It also had strong results when tested on a separate group of patients.

This machine learning tool could become a helpful screening aid for doctors, especially in settings where IgD-specific tests aren’t routinely done. Early detection allows for faster, more personalized treatment and better use of healthcare resources.

 

 

"Evolution of clonal hematopoiesis on and off lenalidomide maintenance for multiple myeloma"

Source

Cooperrider, J.H., Karaoglu, D.A., Kubicki, T. et al. Evolution of clonal hematopoiesis on and off lenalidomide maintenance for multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02707-2 July 16, 2025. 

Overview

Some treatments for multiple myeloma (MM) can raise the risk of developing new blood cancers later on. This letter to the editor discusses how long-term lenalidomide maintenance therapy—often used after autologous stem cell transplant (ASCT)—might contribute to this risk by promoting the growth of dangerous mutations in blood-forming cells.

Multiple myeloma is a cancer that usually relapses over time. Patients often live longer due to better treatments, but this has led to a rise in second primary blood cancers (SPHM), like therapy-related leukemia. Studies suggest about 7% of MM patients may develop an SPHM. Some of these cases may be linked to lenalidomide, a maintenance drug given to keep the cancer in remission.

The researchers focused on a condition called clonal hematopoiesis (CH), where certain mutations appear in blood cells even before cancer develops. CH is more common with age but becomes risky when certain mutations—like in the TP53 gene—are present. These mutated cells can grow faster after patients receive chemotherapy or stem cell transplants, especially under the influence of lenalidomide.

To study this, the team analyzed blood samples from MM patients enrolled in two clinical trials: ATLAS and MRD2STOP. One group stayed on lenalidomide maintenance, and the other stopped after reaching deep remission. Using sensitive genetic tests, they tracked changes in CH mutations over two years.

They found that patients on lenalidomide were more likely to have increasing TP53 mutations, known to be linked with later development of leukemia. In contrast, those who stopped lenalidomide often showed stable or shrinking levels of these mutations. Importantly, some patients who had rising TP53 mutations later developed therapy-related blood cancers.

The findings suggest that long-term use of lenalidomide may encourage the growth of dangerous CH clones in some patients. Stopping lenalidomide, especially after reaching deep remission, may help lower this risk without harming myeloma control.

These results point to a possible way to personalize treatment. By using regular genetic testing to monitor CH over time, doctors might identify patients at higher risk for future blood cancers and adjust maintenance treatment accordingly. While more research is needed, this approach could lead to safer, more targeted care for people living with multiple myeloma.

 

 

"Current and future role of carfilzomib-based quadruplet combinations as therapy for newly diagnosed multiple myeloma"

Source

Landgren, O., Biran, N., O'Donnell, E.K., Mikhael, J., Weisel, K.C., Broijl, A., Usmani, S.Z., Moreau, P., Gay, F.M., Mina, R., Rodríguez-Otero, P., Jakubowiak, A.J. and Derman, B.A. (2025), Current and future role of carfilzomib-based quadruplet combinations as therapy for newly diagnosed multiple myeloma. HemaSphere, 9: e70178. https://doi.org/10.1002/hem3.70178 July 16, 2025.  

Overview

Treatment for newly diagnosed multiple myeloma (NDMM) has improved significantly, with many patients now starting therapy with powerful combinations of drugs. The standard approach often includes a triplet of a proteasome inhibitor (PI), an immunomodulatory drug, and a steroid. A commonly used triplet is Velcade® (bortezomib), Revlimid® (lenalidomide), and dexamethasone (VRd). But another option is a similar combination that replaces bortezomib with a newer PI called Kyprolis® (carfilzomib), known as KRd.

For patients who are healthy enough for a stem cell transplant, KRd is recommended in U.S. treatment guidelines, even though it doesn’t yet have full FDA approval for use in newly diagnosed cases. Some studies are also testing whether adding an anti-CD38 antibody, like Sarclisa® (isatuximab) or daratumumab, to KRd (creating Isa-KRd or D-KRd) can make the treatment even more effective. Early results are promising, showing deep and long-lasting responses, including in patients with high-risk myeloma. Some patients even reach a level called “minimal residual disease negativity,” meaning no signs of cancer can be found using very sensitive tests.

KRd-based combinations may be a good alternative to VRd for certain patients. Ongoing research is looking at how to select the right patients, reduce side effects, and fine-tune the dosing to make KRd-based quadruplets a more common first-line treatment option in multiple myeloma care.

 

 

"Prognostic implications of splenomegaly in BCMA-directed CAR T-Cell therapy for relapsed myeloma"

Source

Thomas Wiemers, Maximilian Ferle, Jonas Ader, Veronika Sotikova, David Fandrei, Nora Grieb, Luise Fischer, Patrick Born, Heike Weidner, Song Yau Wang, Madlen Jentzsch, Georg-Nikolaus Franke, Carmen Herling, Klaus Metzeler, Marco Herling, Simone Heyn, Timm Denecke, Kristin Reiche, Uwe Platzbecker, Vladan Vucinic, Thomas Neumuth, Hans-Jonas Meyer, Maximilian Merz, Prognostic implications of splenomegaly in BCMA-directed CAR T-Cell therapy for relapsed myeloma, Transplantation and Cellular Therapy, 2025, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2025.07.003. July 16, 2025. 

Overview

A new study looked at whether spleen size could help doctors predict how patients with relapsed or refractory multiple myeloma (RRMM) will respond to CAR T-cell therapy. This type of treatment, which targets a protein called BCMA, has helped many patients but can cause serious side effects—especially low platelet counts (thrombocytopenia) and problems linked to the immune system.

Researchers studied 73 patients who had received CAR T-cell therapy and used CT scans to measure their spleen size. They found that patients with larger spleens (a condition called splenomegaly) were more likely to develop severe and long-lasting thrombocytopenia. These patients also had more cancer in their bodies (higher metabolic tumor volume) and higher levels of a blood marker called soluble BCMA (sBCMA), which can signal how active the disease is.

Most importantly, a larger spleen was linked to shorter progression-free survival and overall survival, meaning the cancer came back sooner and patients didn’t live as long. In fact, spleen size turned out to be a better predictor of outcomes than other commonly used tools like sBCMA levels, the EASIX score, or the CAR-HEMATOTOX score.

This research suggests that simply checking spleen size could help doctors better understand each patient's risk, make smarter treatment decisions, and plan for possible complications during CAR T-cell therapy.

 

 

"Iron-dependent cell death: Unlocking ferroptosis as a key to multiple myeloma therapy"

Source

Fatemeh Karimian, Melika Khademi, Amirsalar Nikkhah bahrami, Maryam Nabigol, Fatemeh Mikanik, Mehdi Bakhtiyaridovvombaygi, Nader Vazifeh Shiran, Iron-dependent cell death: Unlocking ferroptosis as a key to multiple myeloma therapy, Clinical Immunology, 2025, 110570, ISSN 1521-6616, https://doi.org/10.1016/j.clim.2025.110570. July 16, 2025. 

Overview

Ferroptosis is a special kind of cell death that depends on iron and causes damage by creating high levels of reactive oxygen species (ROS). These molecules attack the fats in cell membranes, leading to cell breakdown. This happens when the balance between oxidation and the body’s natural defenses is thrown off. In this process, iron and fat metabolism drive the damage, while a protective enzyme called GPX4 usually helps prevent it.

In multiple myeloma—a cancer of plasma cells—researchers have found that the cancer cells are especially sensitive to ferroptosis. That means triggering this type of cell death could be a new way to target and kill myeloma cells. Even though treatments for multiple myeloma have improved, the disease still has a poor long-term outlook. Scientists are now studying how ferroptosis could work together with current drugs, like Velcade®  (bortezomib), to make treatments more effective and potentially improve patient outcomes.

 

 

"Moving Beyond G-CSF Mobilization—Learning From a 15-Year Experience of Different Stem Cell Mobilization Regimens in Multiple Myeloma"

Source

S. Mirgh, B. Bagal, S. Punatar, et al., “Moving Beyond G-CSF Mobilization—Learning From a 15-Year Experience of Different Stem Cell Mobilization Regimens in Multiple Myeloma,” Cancer Medicine 14, no. 14 (2025): e71068, https://doi.org/10.1002/cam4.71068. July 16, 2025. 

Overview

In this 15-year study, doctors looked at different ways to collect stem cells from patients with multiple myeloma before a stem cell transplant. The goal was to find out which method worked best at collecting enough stem cells with the fewest complications. Stem cell mobilization helps move stem cells from the bone marrow into the blood, where they can be collected for transplant. The four regimens studied included different combinations of medications: Bortezomib with G-CSF, G-CSF with Plerixafor, Velcade® (bortezomib) with Cytoxan® (cyclophosphamide) and G-CSF, and Cyclophosphamide with G-CSF.

The results showed that using Cyclophosphamide-based regimens (with or without Bortezomib) led to higher total stem cell yields overall. In fact, the best results came from using all three drugs—Bortezomib, Cyclophosphamide, and G-CSF. This combination not only helped collect more stem cells, but also had no cases of mobilization failure in the study. G-CSF with Plerixafor also performed well, especially when only one collection session was needed. However, using Bortezomib with G-CSF alone was the least effective method and had the highest failure rate.

The study also looked at how factors like prior treatments with lenalidomide or radiation therapy affected results. For patients who had radiation to areas where stem cells are made (like the spine or pelvis), the combination of Bortezomib, Cyclophosphamide, and G-CSF worked better than G-CSF with Plerixafor. Based on these findings, the center now recommends G-CSF with Plerixafor for most patients—but prefers the triple combination if the patient has had radiation to the bone marrow.

Overall, this large study helps guide which mobilization method might work best depending on a patient’s treatment history. While each approach has pros and cons, Cyclophosphamide-based regimens—especially with Bortezomib—offer strong results in collecting enough stem cells for transplant.

 

 

"Microwave assisted solvothermal green synthesis of Fe3O4 nanoparticles using sea buckthorn for multiple myeloma and monocytic leukemia treatment"

Source

Alzaidy, A.H., Ganduh, S.H., Abed, M.J. et al. Microwave assisted solvothermal green synthesis of Fe3O4 nanoparticles using sea buckthorn for multiple myeloma and monocytic leukemia treatment. Sci Rep 15, 25743 (2025). https://doi.org/10.1038/s41598-025-11532-7 July 16, 2025.  

Overview

In this 15-year study, doctors looked at different ways to collect stem cells from patients with multiple myeloma before a stem cell transplant. The goal was to find out which method worked best at collecting enough stem cells with the fewest complications. Stem cell mobilization helps move stem cells from the bone marrow into the blood, where they can be collected for transplant. The four regimens studied included different combinations of medications: Bortezomib with G-CSF, G-CSF with Plerixafor, Velcade® (bortezomib) with Cytoxan® (cyclophosphamide) and G-CSF, and Cyclophosphamide with G-CSF.

The results showed that using Cyclophosphamide-based regimens (with or without Bortezomib) led to higher total stem cell yields overall. In fact, the best results came from using all three drugs—Bortezomib, Cyclophosphamide, and G-CSF. This combination not only helped collect more stem cells, but also had no cases of mobilization failure in the study. G-CSF with Plerixafor also performed well, especially when only one collection session was needed. However, using Bortezomib with G-CSF alone was the least effective method and had the highest failure rate.

The study also looked at how factors like prior treatments with lenalidomide or radiation therapy affected results. For patients who had radiation to areas where stem cells are made (like the spine or pelvis), the combination of Bortezomib, Cyclophosphamide, and G-CSF worked better than G-CSF with Plerixafor. Based on these findings, the center now recommends G-CSF with Plerixafor for most patients—but prefers the triple combination if the patient has had radiation to the bone marrow.

Overall, this large study helps guide which mobilization method might work best depending on a patient’s treatment history. While each approach has pros and cons, Cyclophosphamide-based regimens—especially with Bortezomib—offer strong results in collecting enough stem cells for transplant.

 

 

"Access and Outcomes of Racial and Ethnic Minority Populations Receiving Commercial Anti-BCMA CART for Myeloma"

Source

Luca Paruzzo, Khashayar Eshaghi, Guido Ghilardi, Abigail Doucette, Matthew Ho, Alberto Carturan, Dan T. Vogl, Adam J. Waxman, Shivani Kapur, Eugenio Fardella, Martina Pucillo, Antonio Imparato, Federico Stella, Puneeth Guruprasad, Vitor B. De Souza, Luke Maillie, Sofia Kaparis, Riemke Bouvier Bs, Adam D. Cohen, Jalpa A. Doshi, David L. Porter, Alfred L. Garfall, Edward A. Stadtmauer, Carmen E. Guerra, Sandra P. Susanibar Adaniya, Marco Ruella, Access and Outcomes of Racial and Ethnic Minority Populations Receiving Commercial Anti-BCMA CART for Myeloma, Blood Immunology & Cellular Therapy, 2025, 100007, ISSN 3050-5976, https://doi.org/10.1016/j.bict.2025.100007. July 16, 2025. 

Overview

CAR T-cell therapy targeting BCMA is a powerful treatment for multiple myeloma, but getting access to it isn’t easy—especially for patients from racial and ethnic minority populations (REMPs), who are already more affected by the disease. This study looked at how REMPs are represented among patients receiving this advanced therapy at the Abramson Cancer Center (ACC) and whether their outcomes differ from other patients.

Out of 140 people who received CAR T-cell therapy between 2021 and 2024, only 17% were from REMP backgrounds. That’s much lower than their representation in the general multiple myeloma population in the area, where REMPs made up nearly 34%. The study also found that REMP patients who did get the therapy tended to live closer to the treatment center and were less likely to be married.

Despite these differences in access, the results of the treatment were nearly the same for everyone. REMP patients responded just as well as non-REMPs, with similar rates of cancer control, survival, and side effects. That means the treatment works equally well regardless of race or ethnicity.

The main takeaway? CAR T-cell therapy is effective for all patients, but not everyone is getting a fair chance to receive it. The study points to an urgent need to reduce barriers and improve access for underserved groups so that more patients can benefit from this life-extending treatment.

 

 

"Outcomes of Calcium-Channel Blocker Use in Patients With Multiple Myeloma: A Propensity-Matched Study From the Global Federated Health Research Network"

Source

Eidbo S, Malin J H, Barnett M, et al. (July 16, 2025) Outcomes of Calcium-Channel Blocker Use in Patients With Multiple Myeloma: A Propensity-Matched Study From the Global Federated Health Research Network. Cureus 17(7): e88087. doi:10.7759/cureus.88087 July 16, 2025. 

Overview

This study looked at how calcium channel blockers (CCBs)—a common medication for heart conditions like high blood pressure—might affect people with multiple myeloma. Many multiple myeloma patients already take CCBs for other health problems, but it’s unclear how these drugs might interact with complications of the disease, especially high calcium levels in the blood (hypercalcemia), which is common in myeloma.

Researchers analyzed data from thousands of patients with multiple myeloma over a five-year period, comparing those who were prescribed CCBs to those who were not. They looked at serious health outcomes like kidney damage, the need for dialysis, seizures, heart rhythm problems, ICU admissions, and overall survival.

They found that patients who were not taking CCBs generally had lower risks of kidney problems, seizures, and abnormal heart rhythms—but their risk of death was slightly higher. When looking at specific drugs within the CCB group—like amlodipine, nifedipine, diltiazem, and others—the results varied. Some CCBs were linked to higher survival rates but also came with increased risks of other serious issues, like irregular heartbeats or kidney failure.

Overall, the study suggests that certain CCBs may worsen some complications in multiple myeloma, possibly because of how they interact with calcium levels in the body. More research is needed to fully understand these connections, but this finding highlights the importance of personalized treatment plans and close monitoring for patients with multiple myeloma who are also taking medications for other conditions.

 

 

"Whole body MRI by MY-RADS for imaging response assessment in multiple myeloma"

Source

Messiou, C., Porta, N., Koh, DM. et al. Whole body MRI by MY-RADS for imaging response assessment in multiple myeloma. Blood Cancer J. 15, 122 (2025). https://doi.org/10.1038/s41408-025-01327-4 July 17, 2025. 

Overview

This study looked at how whole-body MRI (WB-MRI) can help detect leftover cancer, or minimal residual disease (MRD), in patients with multiple myeloma after a stem cell transplant. While blood tests and bone marrow biopsies are commonly used to check for MRD, they can sometimes miss signs of disease because they only sample small areas. Imaging with WB-MRI offers a fuller picture of the entire body and may catch disease that other methods miss.

In this clinical trial, 70 patients with newly diagnosed or relapsed multiple myeloma had WB-MRI scans before treatment and again about 100 days after receiving an autologous stem cell transplant. The scans followed the MY-RADS protocol, a standardized method for interpreting MRI results in myeloma.

The findings were clear: patients who still had signs of disease on their MRI after the transplant had worse outcomes. Their cancer returned sooner—on average after 24 months—compared to 42 months or more in those with no detectable disease. They also had shorter overall survival. MRI results added valuable information, helping to fine-tune what doctors already knew from lab tests and bone marrow MRD analysis.

This study supports using WB-MRI as a key tool in checking for residual disease in multiple myeloma. It gives doctors a more complete view of a patient’s response to treatment and helps guide future care.

 

 

"DEK facilitates bortezomib resistance of multiple myeloma by modulating ferroptosis"

Source

Wang, H., Zhang, J., Chen, L. et al. DEK facilitates bortezomib resistance of multiple myeloma by modulating ferroptosis. Clin Exp Med 25, 252 (2025). https://doi.org/10.1007/s10238-025-01673-4 July 17, 2025. 

Overview

Multiple myeloma is the second most common blood cancer, and while treatments have improved, drug resistance remains a major challenge—especially with commonly used medications like Velcade® (bortezomib). This study focused on figuring out why some myeloma cells become resistant to bortezomib and how to possibly overcome that resistance.

Researchers looked at hundreds of genes and identified one in particular—called DEK—that stood out. DEK was found at higher levels in patients with multiple myeloma and in lab-grown myeloma cells that were resistant to bortezomib. When DEK was present in large amounts, myeloma cells were more likely to resist the effects of the drug. However, when DEK was blocked or removed, the cancer cells became more sensitive to treatment, in part because they began a process called ferroptosis—a type of cell death triggered by iron and oxidative stress.

These findings suggest that DEK plays a key role in helping myeloma cells survive bortezomib treatment. Targeting DEK may offer a new way to treat patients whose myeloma no longer responds to this important drug.

 

 

"Exploring the role of cyclin D1 in the pathogenesis of multiple myeloma beyond cell cycle regulation"

Source

Cardona-Benavides, I.J., Cristobal-Vargas, S., De Ramón, C., Rojas, E.A., Misiewicz-Krzeminska, I., Isidro, I., Pérez, J.J., Paiva, B., Puig, N., Alcoceba, M., Mateos, M.-V., Corchete, L.A., Cuadrado, M. and Gutiérrez, N.C. (2025), Exploring the role of cyclin D1 in the pathogenesis of multiple myeloma beyond cell cycle regulation. Mol Oncol. https://doi.org/10.1002/1878-0261.70085 July 17, 2025. 

Overview

Although multiple myeloma isn’t known for rapid cell growth like some cancers, this study looked at a group of proteins called cyclins D—especially cyclin D1 and D2—to see if they play other roles in how the disease behaves. Cyclins D are usually linked to cell division, but researchers suspected they might be doing more in multiple myeloma.

In lab tests, when cyclin D1 or D2 was added to myeloma cells that didn’t have them, they didn’t cause the cells to multiply faster. Instead, cyclin D1 showed up in parts of the cell where it usually isn’t found and affected how the cells interact with their environment. Specifically, it changed how myeloma cells stuck to surrounding tissues and reduced levels of CD56—a protein that helps cells stay in place. This was confirmed in a group of 85 patients, where most people with high cyclin D1 had low or no CD56. These patients were also more likely to have cancer cells circulating in their blood, suggesting the disease may spread more easily.

The study shows that cyclin D1 may help myeloma cells break away and move through the body, not just grow. This new insight could lead to better ways of understanding how the disease spreads and how to treat it.

 

 

"Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells"

Source

Xinlong Guo, Xuelian Ren, Cong Yan, He Huang, Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells, ACS Chemical Biology, 2025,ISSN 1554-8937, https://doi.org/10.1021/acschembio.5c00270. July 23, 2025. 

Overview

Multiple myeloma (MM) is a blood cancer caused by the buildup of abnormal plasma cells. Revlimid® (lenalidomide) is a key treatment, but over time, many patients stop responding to it. This study looked into why that happens, focusing on a type of protein change called lysine lactylation (Kla), which hasn’t been studied much in MM.

Researchers found that lenalidomide-resistant MM cells had higher Kla levels, especially when driven by increased glycolysis—a process cancer cells often use for energy. When they blocked glycolysis, the cancer cells became sensitive to lenalidomide again. Using advanced protein analysis, the team studied thousands of proteins and identified changes in Kla and acetylation patterns. They found that several proteins linked to drug resistance were more active, while others tied to the drug’s target, CRL4-CRBN, were less active.

One key discovery was that histone H4 with a Kla modification at position K8 (H4K8la) was linked to higher levels of two genes—CDK6 and ECHS1—that help MM cells resist treatment. These findings suggest Kla plays a major role in how MM cells become resistant to lenalidomide, offering a possible path to reverse resistance and improve treatment outcomes.

 

 

"Rewriting Risk: A Data-Driven Look at Myeloma Genetics"

Source

Krina Patel et al. Rewriting Risk: A Data-Driven Look at Myeloma Genetics. JCO 0, JCO-25-00988 DOI:10.1200/JCO-25-00988 July 18, 2025. 

Overview

Over the past 20 years, treatment for multiple myeloma has improved dramatically, more than doubling survival for many patients. But there’s still a serious challenge: people with high-risk myeloma, especially those with what's now called double-hit myeloma. These patients have two or more high-risk genetic abnormalities and tend to have worse outcomes, even with the best current therapies.

A new 2024 expert consensus from the International Myeloma Society (IMS) and the International Myeloma Working Group (IMWG) now provides an updated way to identify high-risk patients using modern genetic testing. Instead of looking at single mutations alone, this new model uses combinations of genetic changes—including del(17p), TP53 mutations, and certain changes on chromosomes 1 and 14—to define risk more accurately. These combinations, especially when two or more are present, make up what’s now known as double-hit myeloma, previously referred to as ultra-high-risk myeloma.

Backed by a massive international meta-analysis of more than 13,900 patients across 24 clinical trials, the new staging system clearly shows that double-hit patients do far worse than those with only one or no high-risk changes. They relapse sooner and have shorter overall survival, regardless of treatment type or where the study was done. These results confirm the importance of expanded genetic testing at diagnosis and relapse to catch these high-risk cases early.

Even though we now better understand who is at higher risk, treating these patients remains tough. Standard treatments, including stem cell transplants and powerful drug combinations, don’t work as well in double-hit myeloma. That’s why researchers and doctors are calling for risk-adapted care, meaning treatment should be personalized based on a patient’s genetic risk. Clinical trials for high-risk patients are now focusing on more aggressive and innovative options, like CAR T-cell therapy and bispecific antibodies, which show early promise.

Current best treatments for newly diagnosed high-risk patients often involve a four-drug combination that includes carfilzomib, an autologous stem cell transplant, and dual maintenance therapy (such as lenalidomide plus a CD38 antibody). For relapsed high-risk cases, early use of CAR T or bispecifics is recommended. However, frail patients may need adjusted doses or more carefully designed treatment plans.

In short, this new classification system and the supporting global data give doctors better tools to spot high-risk multiple myeloma sooner and more clearly. The next step is making sure this knowledge shapes how patients are treated, especially those with double-hit myeloma, who still face the greatest risk and the fewest durable options. The goal is clear: smarter risk detection, better therapy choices, and, ultimately, longer lives for the people who need it most.

 

 

"MIR4726EccDNA drives bortezomib resistance in multiple myeloma by enhancing MIR4726-5p/NXF1/NKIRAS2 axis dependent autophagy"

Source

Li, F., Long, X., Tang, S. et al. MIR4726EccDNA drives bortezomib resistance in multiple myeloma by enhancing MIR4726-5p/NXF1/NKIRAS2 axis dependent autophagy. Cell Commun Signal 23, 346 (2025). https://doi.org/10.1186/s12964-025-02340-7  July 18, 2025. 

Overview

Researchers studying why multiple myeloma (MM) sometimes stops responding to treatment have found a new clue. They focused on a tiny piece of genetic material called extrachromosomal circular DNA (EccDNA), which floats outside normal chromosomes and can influence how cancer behaves. In one patient who had relapsed after treatment and had a specific chromosome deletion (called del(17p)), they discovered a unique EccDNA named MIR4726EccDNA.

This EccDNA appears to help myeloma cells resist bortezomib, a common drug used to treat MM. The researchers showed that this EccDNA can produce a type of microRNA—MIR4726-5p—that starts a chain reaction inside the cancer cells. This reaction boosts levels of a protein called NKIRAS2, which in turn activates a system in the cells known as the NF-κB pathway. This pathway increases autophagy, a process cells use to survive stress, including chemotherapy. The result? The cancer cells become tougher and more resistant to bortezomib.

To back up these findings, the scientists tested the EccDNA in mice with human myeloma tumors. When they boosted levels of MIR4726-5p and treated the tumors with bortezomib, the tumors grew faster and were less responsive to the drug.

This study shows that MIR4726EccDNA plays a role in making multiple myeloma harder to treat by helping cancer cells survive therapy. Understanding how this process works could lead to new strategies to overcome drug resistance in the future.

 

 

"Quantifying Preferences for CAR-T Compared to Standard of Care as a First-Line Treatment Among Patients With Multiple Myeloma"

Source

J. Sutphin, T. W. LeBlanc, E. Janssen, et al., “Quantifying Preferences for CAR-T Compared to Standard of Care as a First-Line Treatment Among Patients With Multiple Myeloma,” Cancer Medicine 14, no. 14 (2025): e71072, https://doi.org/10.1002/cam4.71072.  July 19, 2025. 

Overview

A recent study looked at how people with newly diagnosed multiple myeloma (NDMM) feel about the risks and benefits of early treatment with advanced therapies like CAR-T. While CAR-T is already used for relapsed or hard-to-treat myeloma, researchers wanted to understand how patients weigh the trade-offs when it’s used earlier in treatment, especially when it comes to avoiding long-term maintenance therapy and its daily life impact.

The study asked adults to choose between different made-up treatment options, comparing things like time without relapse, side effects, and how much treatments interfere with daily life. The goal was to see what matters most to patients and how much risk they are willing to accept for more time without the disease coming back.

Most patients said they’d rather have longer periods without relapse, even if it meant facing some serious but rare side effects like hospitalization due to ICANS or CRS (inflammatory reactions that can happen with CAR-T). For example, some said they’d accept a 30% chance of being hospitalized with side effects if it meant two extra years without relapse and only minor life disruptions—so long as there was no added risk of treatment-related death. Others would accept some risk of death to avoid other side effects.

The study found that not everyone thinks the same. About two-thirds of participants were willing to balance risks and benefits, while others were more cautious, especially about treatments that carry any risk of early death. These findings show how important it is for doctors and patients to have clear, personalized conversations when deciding on treatment plans for multiple myeloma.

 

 

"PET radiopharmaceuticals beyond 2-[18F]FDG for the evaluation of multiple myeloma and smoldering multiple myeloma"

Source

Travascio, L., Morales-Lozano, M.I., Guglielmo, P. et al. PET radiopharmaceuticals beyond 2-[18F]FDG for the evaluation of multiple myeloma and smoldering multiple myeloma. Clin Transl Imaging (2025). https://doi.org/10.1007/s40336-025-00714-y  July 19, 2025. 

Overview

This review looked at new and alternative imaging tools being studied for multiple myeloma (MM) and smoldering multiple myeloma (SMM). Specifically, it focused on radiopharmaceuticals—special radioactive tracers used in PET scans—that are different from the commonly used FDG tracer. FDG has been the standard, but researchers are exploring whether other tracers might do a better job at spotting disease earlier or more clearly.

The researchers reviewed 28 clinical studies using newer tracers like methionine, fluciclovine, choline, and several others. Some of these may better target cancer cells or bone activity in MM. They also looked at early research on newer targets like CD-138, VLA-4, BCMA, and nanoparticles, which are being studied in lab models but not yet widely tested in patients.

Overall, these newer tracers could offer clearer or more specific images compared to FDG. But for now, their use in everyday care is limited. Many are expensive, hard to get, or not yet proven in large studies. More research is needed to understand how these tools could be used in the future, especially in personalized care or combining diagnosis and treatment in one step—something called theragnostics.

 

 

"Treatment patterns of patients with multiple myeloma in a real-world setting in Spain. How are triple-class exposed patients being managed?"

Source

Julia Llinares, Sofía Toribio-Castelló, Luis Fernando García, Tamara Iglesias, Ana Heredero, Pablo Rebollo, Isabel Ricote, María Victoria Mateos, Treatment patterns of patients with multiple myeloma in a real-world setting in Spain. How are triple-class exposed patients being managed?, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.07.008. July 19, 2025. 

Overview

This study looked at how multiple myeloma (MM) is being treated in Spain, with a focus on patients who have already been exposed to the three main classes of MM drugs, known as triple-class exposed (TCE) patients. These patients have fewer treatment options left and are harder to treat.

Researchers reviewed real-world data from over 1,200 MM patients between October 2022 and September 2023. About 60% were newly diagnosed, while the rest had relapsed or refractory MM (RRMM). For RRMM patients, treatments varied widely. Most started with lenalidomide-based regimens in the second round of treatment and switched to pomalidomide-based regimens in later rounds. In fact, among patients who had gone through three or more lines of therapy, there were 82 different treatment combinations, showing just how complex and personalized treatment has become.

They found that 27.4% of all patients were already triple-class exposed, and this number increased the more treatments a patient had received. While only around 7% were TCE at the start of their current treatment, over 60% of those in their third or later round of therapy were TCE.

This growing number of TCE patients highlights the urgent need for new treatments that work in different ways. These options will be essential to help doctors better manage the disease, no matter how many treatments a patient has already received.

 

 

"Advances in RNA therapeutics and its delivery strategies against Multiple Myeloma"

Source

Kaiwen Luo, Zhongkun Zhang, Siyu Yao, Yufei Wang, Mansoor Amiji, Kenneth C. Anderson, Advances in RNA therapeutics and its delivery strategies against Multiple Myeloma, Journal of Controlled Release, 2025, 114048, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2025.114048. July 19, 2025. 

Overview

Multiple myeloma (MM) is a long-term blood cancer that, despite many treatment advances, still has no cure. Most patients eventually relapse or stop responding to current treatments. While new options like targeted drugs, antibodies, and cell therapies have improved care, the disease continues to change and adapt at the molecular level, making it hard for treatments to stay effective.

This review looks at a promising new approach: RNA therapeutics. These treatments work by either blocking or boosting specific RNA molecules inside cancer cells to stop tumor growth. When combined with other treatments, RNA therapies may help MM cells become more sensitive to drugs and improve how well patients respond.

However, there are still challenges. Scientists are still figuring out which RNA targets work best in MM and how to safely and effectively deliver these therapies into the body. This review outlines the current barriers and opportunities, showing how RNA-based treatments could play a big role in the future of MM care, if the right delivery systems and molecular targets can be developed.

 

 

"Perspectives on exercise among individuals with metastatic bone disease and multiple myeloma: a qualitative interview study"

Source

Miller, C., Lane, K., Stuart-Hill, L. et al. Perspectives on exercise among individuals with metastatic bone disease and multiple myeloma: a qualitative interview study. Support Care Cancer 33, 703 (2025). https://doi.org/10.1007/s00520-025-09701-5  July 19, 2025.  

Overview

People living with multiple myeloma (MM) or metastatic bone disease (MBD) often deal with bone damage, which can raise the risk of painful fractures. This understandably affects how they feel about staying physically active. A recent study explored how patients with MM and MBD view physical activity (PA) and what kinds of support they might need to stay active.

Researchers interviewed 20 people—most of them men—who had been diagnosed with either MM or MBD. Some had bone pain, especially during movement, but others had none at all. While many participants were physically active at different levels of intensity, about a quarter led mostly sedentary lifestyles. Still, most recognized that regular movement helped improve their health and quality of life.

The study found that people with MM and MBD are generally open to being active and want exercise to be part of their cancer care. Participants shared their thoughts on what PA means to them, what motivates or holds them back, and what kind of exercise programs they’d prefer. The main takeaway: there’s no one-size-fits-all plan. But with the right support, these patients can overcome barriers to physical activity and enjoy its full benefits—physically, mentally, and emotionally.

 

 

"Multiple Myeloma: Real-world Data on the Clinical Presentation and Outcomes From Oman"

Source

Al Nabhani, I., Al Lawati, J., Al Mahrooqi, N., Al Rawahi, A., Kumar, V., Al Riyami, N., Al Waili, K., Jabeen, Z., Al-Riyami, A.Z., Khan, H., Al Huneini, M., Al Busaidi, T., Al Kindi, S., Al Khabori, M., Al Abri, M., Fawaz, N. and Al Farsi, K. (2025), Multiple Myeloma: Real-world Data on the Clinical Presentation and Outcomes From Oman. eJHaem, 6: e70096. https://doi.org/10.1002/jha2.70096  July 21, 2025. 

Overview

A study from Sultan Qaboos University Hospital in Oman looked at how multiple myeloma (MM) presents and progresses in Omani patients. This kind of data has been limited in the region, so the study offers important insight into how MM affects people locally.

Researchers reviewed records from 98 patients diagnosed and treated for MM between 2008 and 2018. The average age at diagnosis was 61, which is younger than what’s typically seen in global studies. Half the patients were male. The most common type of myeloma was immunoglobulin G (IgG), followed by IgA, and a small number had rare forms like light chain or IgD myeloma. At the time of diagnosis, the most common symptoms were anemia, bone damage (lytic lesions), kidney problems, and high calcium levels. Almost half of the patients had advanced-stage (ISS stage III) disease when they were diagnosed.

Patients received a range of first-line treatments, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), or a combination of both. After a median follow-up of over six years, the study found that the average time without disease progression (progression-free survival) was nearly five years. The average overall survival was just over nine years, but those diagnosed at later stages had much shorter survival.

The study shows that MM patients in Oman tend to be diagnosed at a younger age but with more advanced disease. The researchers recommend more collaboration with other hospitals in the region to better understand MM outcomes and improve care through larger studies.

 

 

"Downregulation of CLEC2 Facilitates the Proliferation and Migration of Multiple Myeloma Cells via Regulating HIF-1α-Mediated Ferroptosis"

Source

Zhu, F., Hang, L., Zhang, P., Yuan, Y., Shen, J. and Zhang, F. (2025), Downregulation of CLEC2 Facilitates the Proliferation and Migration of Multiple Myeloma Cells via Regulating HIF-1α-Mediated Ferroptosis. Journal of Biochemical and Molecular Toxicology, 39: e70387. https://doi.org/10.1002/jbt.70387  July 20, 2025. 

Overview

This study looked at a protein called CLEC2 and its role in multiple myeloma (MM), especially in how it might affect a type of cell death called ferroptosis. Ferroptosis is a process where cells die due to damage from iron and harmful molecules called reactive oxygen species (ROS). In recent years, scientists have discovered that MM cells may survive longer by avoiding ferroptosis.

The researchers found that CLEC2 levels are much lower in MM cells compared to normal plasma cells. When they increased CLEC2 levels in MM cells, those cells became less active—they didn’t grow or move as much. They also showed signs of ferroptosis: more ROS and iron, and changes in several key proteins related to cell damage and survival. On the flip side, when CLEC2 was blocked, MM cells grew more, moved more, and showed fewer signs of ferroptosis.

Further testing showed that CLEC2’s effects are tied to a protein called HIF-1α, which helps cancer cells survive low-oxygen conditions. Blocking ferroptosis or increasing HIF-1α levels canceled out CLEC2’s ability to slow down MM cell growth.

The study suggests that low levels of CLEC2 help MM cells grow and spread by protecting them from ferroptosis. Boosting CLEC2—or targeting the pathways it affects—could be a potential strategy for future MM treatments.

 

 

"Management of Relapsed/ Refractory Myeloma in Resource Constrained Setting: Median age (years)Age (Years)Immunoglobulin subtypeHb (G/dl)Serum creatinine eGFR ml/minute Serum Albumin (g/dl) Serum LDH Platelets countsCirculating plasma cells Cytogenetics Hypercalcemia Comorbidities Diabetes Hypertension Hypothyroidism F/H of malignancy"

Source

Chandraprakash Prasad, Ritu Gupta, Management of Relapsed/ Refractory Myeloma in Resource Constrained Setting: Median age (years)Age (Years)Immunoglobulin subtypeHb (G/dl)Serum creatinine eGFR ml/minute Serum Albumin (g/dl) Serum LDH Platelets countsCirculating plasma cells Cytogenetics Hypercalcemia Comorbidities Diabetes Hypertension Hypothyroidism F/H of malignancy, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.07.007. July 21, 2025. 

Overview

Treating relapsed or refractory multiple myeloma (MM) can be complicated. Doctors have to consider how the disease is behaving, how the patient is doing overall, and what treatments have already been used. This study looked at how well different salvage therapies—which are treatments given after the cancer comes back—worked in patients with relapsed or refractory MM.

Researchers reviewed the records of 195 patients treated between 2014 and 2019. Most patients were symptomatic and received treatment, but 61 patients who showed only signs of disease on lab tests (called biochemical relapse) were monitored closely without starting new therapy right away.

More than half of the patients responded to treatment. About 11% had a complete response (CR), meaning no signs of active disease. Patients who reached CR had much longer periods without disease progression—over 31 months—compared to less than 9 months for others. Those whose cancer was refractory, meaning it didn’t respond to the last treatment, had shorter progression-free survival (PFS), averaging just over 5 months.

The most common serious side effects were low platelet counts, anemia, and fever-related infections. A small number of patients had to stop or change treatment due to side effects.

In summary, patients who had a strong response to salvage therapy—especially those who reached complete remission—had better outcomes. For those without symptoms but showing early signs of relapse, careful monitoring may be enough for a while. The study also highlights the need for new treatment options for patients with disease that doesn’t respond to standard therapies.

 

 

"AI-based body composition analysis of CT data has the potential to predict disease course in patients with multiple myeloma"

Source

Wegner, F., Sieren, M.M., Grasshoff, H. et al. AI-based body composition analysis of CT data has the potential to predict disease course in patients with multiple myeloma. Sci Rep 15, 26455 (2025). https://doi.org/10.1038/s41598-025-11560-3  July 21, 2025. 

Overview

Researchers studied how an AI tool that measures body composition from routine CT scans might help doctors better understand and treat multiple myeloma. They looked at 91 patients and used this tool to measure things like body fat, muscle, and bone density. They then compared those results with each patient’s medical data and outcomes.

The study found that patients who had lower amounts of fat under the skin and overall body fat were more likely to have worse outcomes, including disease progression or death. Using the AI tool, the researchers grouped patients into two types based on their body composition. One group had a much better chance of surviving than the other.

Interestingly, this body composition data didn't always match with traditional risk categories used in multiple myeloma. But when the researchers combined the AI measurements with existing clinical data, the predictions about disease progression were more accurate than using standard risk factors alone.

This study suggests that AI-powered body scans could become a valuable part of tracking and treating multiple myeloma, helping to better predict which patients may need more aggressive care.

 

 

"BCMA-targeting BiTE molecule AMG 420 in relapsed or refractory multiple myeloma: a phase 1b open-label expansion study"

Source

Rodriguez, C., Rodriguez, T., Kentos, A., Driessen, C., Suanmi, K., Lesokhin, A. M., … Quach, H. (2025). BCMA-targeting BiTE molecule AMG 420 in relapsed or refractory multiple myeloma: a phase 1b open-label expansion study. Leukemia & Lymphoma, 1–10. https://doi.org/10.1080/10428194.2025.2528115  July 21, 2025. 

Overview

AMG 420 is a new type of drug designed to help the immune system fight multiple myeloma. It works by connecting T cells—your body’s natural defenders—directly to myeloma cells, helping the immune system attack the cancer more effectively. This study tested AMG 420 on patients whose myeloma had come back or stopped responding to other treatments.

Twenty-three patients received the drug through a continuous IV over a 6-week cycle. Some patients experienced side effects, including fever, headache, and a condition called cytokine release syndrome (CRS), which can happen when the immune system becomes very active. Two serious side effects were reported: a bacterial infection and repeated CRS.

Despite these risks, the treatment showed encouraging results. About 35% of patients responded to the drug, and nearly 9% had no detectable signs of cancer after treatment. On average, patients went nearly three months without their disease getting worse. These early results suggest that AMG 420 and similar T-cell engager therapies could become a powerful new option for treating multiple myeloma, especially by targeting a protein on cancer cells called BCMA.

 

 

"Pharmacovigilance and signal detection of adverse drug events associated with proteasome inhibitors in multiple myeloma: a real-world analysis using the FAERS database"

Source

Luo, J., Chen, S., Zhang, M., Gao, Y., & Zeng, Y. (2025). Pharmacovigilance and signal detection of adverse drug events associated with proteasome inhibitors in multiple myeloma: a real-world analysis using the FAERS database. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2534758 July 21, 2025. 

Overview

Proteasome inhibitors—drugs like Bortezomib, Carfilzomib, and Ixazomib—have played a big role in improving outcomes for people with multiple myeloma. But while these treatments are effective, researchers wanted to better understand how they affect patients in everyday, real-world use—not just in clinical trials.

To do this, they reviewed more than 47,000 reports of side effects submitted to the FDA between 2004 and the end of 2024. The data showed that all three drugs were linked to a wide range of side effects, especially involving the blood, nervous system, heart, liver, and digestive system.

The study also found new potential side effects that haven’t yet been listed on drug labels. These included muscle weakness with Bortezomib, a drop in all types of blood cells (pancytopenia) with Carfilzomib, and memory or thinking issues with Ixazomib. Most of these side effects appeared within the first 30 days of starting treatment.

These findings show the importance of close monitoring, especially in the early stages of treatment, and support the need for ongoing updates to drug safety information based on real-world patient experiences.

 

 

"DOT1L inhibition reprograms innate immunity to potentiate immunomodulatory drug responses in multiple myeloma"

Source

LKazuya Ishiguro, Hiroshi Kitajima, Takeshi Niinuma, Reo Maruyama, Tomohide Tsukahara, Yoshihiko Hirohashi, Akari Takaya, Kohei Kumegawa, Ayano Yoshido, Shohei Sekiguchi, Hajime Sasaki, Akira Yorozu, Mutsumi Toyota, Masahiro Kai, Toshihiko Torigoe, Hiroshi Nakase, Hiromu Suzuki, DOT1L inhibition reprograms innate immunity to potentiate immunomodulatory drug responses in multiple myeloma, Cancer Letters, 2025, 217941, ISSN 0304-3835, https://doi.org/10.1016/j.canlet.2025.217941. July 21, 2025. 

Overview

Lenalidomide is a key drug used to treat multiple myeloma, but it doesn’t always work as well as doctors would like. Researchers are now exploring ways to make it more effective. One approach involves targeting a protein called DOT1L, which helps control how genes are turned on or off in cells.

In this study, scientists found that multiple myeloma cells depend heavily on DOT1L to survive. When DOT1L was blocked, the cancer cells activated a natural immune response—specifically, a type of response linked to interferons, which are proteins that help fight infections and cancer. Blocking DOT1L also caused stress to the DNA in myeloma cells and increased activity in the STING pathway, a key part of the body’s built-in immune defense.

The study also showed that stopping DOT1L reduced levels of proteins like IRF4 and IKZF1/3, which are important for myeloma cell growth. Most importantly, when DOT1L inhibitors were combined with lenalidomide, the treatment worked even better. This combination boosted immune activity inside the cancer cells and made them more sensitive to treatment.

These findings suggest that targeting DOT1L could make existing treatments like lenalidomide more powerful and offer a new way to fight multiple myeloma by turning the cancer’s own biology against it.

 

 

"Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Modeling of Serum M-Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma"

Source

C. Li, A. Santulli, S. Van Wart, et al., “Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Modeling of Serum M-Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma,” Clinical and Translational Science 18, no. 7 (2025): e70296, https://doi.org/10.1111/cts.70296.  July 21, 2025.  

Overview

Modakafusp alfa (TAK-573) is a new type of treatment being tested for people with relapsed or refractory multiple myeloma, meaning their cancer has returned or isn’t responding to other therapies. This drug is designed to boost the body’s immune response against myeloma cells by combining a CD38-targeting antibody with a form of interferon, a protein that activates immune cells.

In a clinical trial with 96 patients, researchers studied how the drug moves through the body (pharmacokinetics) and how it affects tumor activity by measuring levels of M-protein in the blood—a key marker of myeloma. They found that the drug's behavior in the body changes over time, partly due to the development of antibodies against the drug itself. They also discovered that body weight affects how the drug spreads in the body, but not how it's broken down or removed.

The results helped researchers choose the best dosing strategy. Instead of adjusting the dose based on a patient’s weight, they found that fixed doses work just as well. This finding guided the next phase of the trial and supported ongoing efforts to fine-tune dosing for better treatment outcomes. Overall, these results help move modakafusp alfa closer to becoming a possible new option for people with hard-to-treat multiple myeloma.

 

 

"A quantum machine learning framework for predicting drug sensitivity in multiple myeloma using proteomic data"

Source

Priyadharshini, M., Raju, B.D., Banu, A.F. et al. A quantum machine learning framework for predicting drug sensitivity in multiple myeloma using proteomic data. Sci Rep 15, 26553 (2025). https://doi.org/10.1038/s41598-025-06544-2  July 22, 2025.  

Overview

Researchers have developed a new tool called QProteoML that uses quantum machine learning to predict how well multiple myeloma patients might respond to treatment. Multiple myeloma is a very complex disease, and not all patients respond the same way to common treatments like proteasome inhibitors and immunomodulatory drugs. Predicting which patients will benefit from which drugs has been a major challenge, especially because the biological data involved is so detailed and complicated.

Traditional computer models often struggle with this kind of data because it has too many features and too few patient samples. That leads to problems like overfitting and inaccurate predictions. QProteoML uses quantum computing techniques to overcome these issues. It combines several advanced quantum tools to reduce the data’s complexity, improve pattern recognition, and balance uneven data, such as when only a small number of patients are drug-resistant.

In tests comparing QProteoML to standard machine learning models, the quantum version did a better job at correctly identifying patients who are resistant to treatment—a group that is often harder to detect. It also highlighted specific proteins linked to drug response, making the results more useful for doctors and researchers.

This technology could bring us closer to truly personalized treatment plans for multiple myeloma, helping match the right therapy to each patient more accurately. While more testing in real-world settings is needed, QProteoML shows strong potential to improve care through smarter, more precise predictions.

 

 

"Bispecific anti-CD38/CD28 antibodies for treatment of multiple myeloma"

Source

Perez-Santos, M., Anaya-Ruiz, M., Flores-Robles, D., Millán-Vega, A., & Sierra-Martínez, P. (2025). Bispecific anti-CD38/CD28 antibodies for treatment of multiple myeloma. Pharmaceutical Patent Analyst, 1–6. https://doi.org/10.1080/20468954.2025.2535944 July 22, 2025. 

Overview

Researchers are exploring a new type of antibody treatment for multiple myeloma that targets a protein called CD38, which is found in high amounts on myeloma cells. A recent patent describes two bispecific antibodies—bsAb6031 and bsAb7945—that are designed to target both CD38 and another immune-related protein called CD28.

In lab tests, these new antibodies helped activate the immune system by boosting the activity of CD4+ and CD8+ T cells, which are key players in attacking cancer cells. They also triggered the release of immune signaling proteins like IFN-γ, IL-2, and TNF-α, which help the body fight tumors. While the antibodies showed promising results in killing myeloma cells in the lab, they were less effective when tested alone in live animal models.

However, combining these anti-CD38/CD28 antibodies with another type of bispecific antibody that targets BCMA and CD3 showed stronger results in shrinking tumors. This suggests that the best use of these antibodies may be in combination therapies, rather than as stand-alone treatments.

While more research and clinical testing are needed, this approach could offer a new strategy for enhancing the immune system’s ability to fight multiple myeloma, especially in patients who don’t respond well to current therapies.

 

 

"Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders"

Source

Zanwar, S., Rajkumar, S.V. Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders. Leukemia (2025). https://doi.org/10.1038/s41375-025-02654-y  July 23, 2025.  

Overview

Clonal plasma cell disorders include a range of conditions such as multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), Waldenström macroglobulinemia (WM), and AL amyloidosis. These disorders all involve abnormal plasma cells, but each behaves differently and carries a unique risk of progression.

For MGUS, SMM, and MM, the chance of disease worsening depends on several factors. These include how many abnormal cells are present, changes in the cells’ DNA (cytogenetics), the environment inside the bone marrow, and the patient’s overall health. Waldenström macroglobulinemia is usually slow-growing but has its own unique genetic changes and unpredictable outcomes. AL amyloidosis is especially influenced by which organs are affected and how severely.

This summary comes from a review that looks at how doctors currently assess risk in these conditions. It explains the pros and cons of the tools used to predict disease progression and offers guidance on how best to apply them in real-life care. Understanding these differences helps doctors personalize treatment and monitoring plans for each patient.

 

 

"Development and Preclinical Validation of a Novel 89Zr-Labeled BCMA-Targeting Antibody for ImmunoPET Imaging: Application in Multiple Myeloma Models and First-In-Nonhuman-Primates"

Source

Tianyao Wang, Qi Yang, Wenpeng Huang, Xinyao Sun, Youlan Lei, Hui Xu, Lele Song, Xiaojiang Duan, Futao Liu, Wenzhi Wang, Zheng Bao, Jinquan Gao, Feng Wang, Lei Kang, Development and Preclinical Validation of a Novel 89Zr-Labeled BCMA-Targeting Antibody for ImmunoPET Imaging: Application in Multiple Myeloma Models and First-In-Nonhuman-Primates, Journal of Medicinal Chemistry, 2025, ISSN 1520-4804, https://doi.org/10.1021/acs.jmedchem.5c01010. July 23, 2025. Zanwar, S., Rajkumar, S.V. Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders. Leukemia (2025). https://doi.org/10.1038/s41375-025-02654-y  July 23, 2025.  

Overview

Researchers have developed a new imaging tool to help track multiple myeloma using a molecule that targets BCMA, a well-known marker found on myeloma cells. This new tool is based on a humanized monoclonal antibody that binds to BCMA. Scientists attached a special imaging agent called zirconium-89 to the antibody, creating a tracer named [89Zr]Zr-DFO-PFBH0L0. In lab tests, this tracer showed strong and stable binding to myeloma cells that express BCMA.

When tested in animals, the tracer successfully located myeloma tumors and showed high uptake in the cancer cells, with very little found in the blood, meaning it was highly specific. It worked especially well in a mouse model carrying human myeloma cells, clearly lighting up tumors on PET scans. For the first time, researchers also tested this tracer in nonhuman primates and found that it behaved safely and predictably, moving through the body in a way that suggests it could work well in people.

Overall, this study shows that [89Zr]Zr-DFO-PFBH0L0 could become a powerful new way to noninvasively image multiple myeloma throughout the body. It may help doctors better detect and monitor the disease, offering a new option for tracking treatment and disease progression in patients with BCMA-positive myeloma.

 

 

"Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cell"

Source

Xinlong Guo, Xuelian Ren, Cong Yan, He Huang, Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells, ACS Chemical Biology, 2025,ISSN 1554-8937, https://doi.org/10.1021/acschembio.5c00270. July 23, 2025.

Overview

Researchers are studying why some multiple myeloma (MM) patients become resistant to Revlimid® (lenalidomide), a common and effective treatment. Over time, many patients stop responding to the drug, and scientists want to understand why this happens. One focus of this study is on protein changes inside cells, called post-translational modifications (PTMs), which can affect how cancer cells grow and respond to treatment. In this case, the researchers looked closely at a specific type of PTM called lysine lactylation (Kla), which appears to increase in myeloma cells that are resistant to lenalidomide.

They found that higher levels of Kla are linked to increased glycolysis, the process cells use to make energy. When they blocked glycolysis, the resistant cells became more sensitive to lenalidomide again. Using advanced tools to study proteins in the cells, the researchers identified thousands of proteins and PTM sites, showing major differences between resistant and non-resistant cells. Some important resistance-related proteins were found to have higher Kla levels, suggesting Kla plays a key role in drug resistance. One key discovery was that a marker called histone H4K8la is tied to higher levels of two genes linked to resistance: CDK6 and ECHS1. This study helps explain how MM cells become resistant to lenalidomide and opens the door to potential new strategies to reverse resistance and improve treatment outcomes.

 

 

"A BCMA-mRNA vaccine is a promising therapeutic for multiple myeloma"

Source

Debasmita Dutta, Jiye Liu, Kenneth Wen, Arghya Ray, Alessandro Salatino, Xiangdong Liu, Annamaria Gulla, Teru Hideshima, Yan Song, Kenneth C. Anderson; A BCMA-mRNA vaccine is a promising therapeutic for multiple myeloma. Blood 2025; blood.2025028597. doi: https://doi.org/10.1182/blood.2025028597  July 23, 2025. 

Overview

Scientists have created a new type of cancer vaccine designed to treat multiple myeloma by targeting a protein called BCMA, which is commonly found on myeloma cells. Inspired by the success of mRNA vaccines for COVID-19, they developed a BCMA mRNA vaccine packaged in lipid nanoparticles (LNPs) to help it reach the spleen, where immune responses are often activated. They also included an immune-boosting molecule called Poly(I:C) to strengthen the body’s reaction to the vaccine.

In lab tests, the vaccine helped dendritic cells—immune cells that kickstart the body’s defenses—activate T cells that specifically attacked BCMA-positive myeloma cells, while leaving healthy cells alone. In mouse models, the vaccine triggered strong immune responses and led to a reduction in tumor growth. The addition of Poly(I:C) made these immune effects even stronger. This early research suggests that BCMA mRNA vaccines could offer a new way to treat multiple myeloma by training the immune system to recognize and destroy cancer cells.

 

 

"HLA-E[pHLA-G] Complex Specific Monoclonal Antibody Enhancing NK Activity in Multiple Myeloma"

Source

Muhammad Abu Ahmad, Olga Radinsky, Bar Kaufman, Kamran Waidha, Eman Gharra, Sharon Dim, Dinesh Babu Manikandan, Noa Ofir, Dirk Jäger, Marten Meyer, Moshe Elkabets, Kerry S. Campbell, Miri Zektser, Roi Gazit, Ory Rouvio, Frank Momburg, Angel Porgador; HLA-E[pHLA-G] Complex Specific Monoclonal Antibody Enhancing NK Activity in Multiple Myeloma. Blood Adv 2025; bloodadvances.2025016276. doi: https://doi.org/10.1182/bloodadvances.2025016276  July 24, 2025. 

Overview

Researchers have developed a new immune therapy that may help the body fight multiple myeloma more effectively, while causing fewer side effects. Normally, a molecule called HLA-E on tumor cells can shut down natural killer (NK) cells and CD8+ T cells by interacting with a receptor called NKG2A. Blocking this interaction has shown promise in cancer treatment, but it can also affect healthy cells, leading to unwanted toxicity.

To solve this problem, scientists created a new monoclonal antibody called 4D7 that targets a specific version of HLA-E found mostly on cancer cells. In lab tests using bone marrow samples from multiple myeloma patients, 4D7 was able to block the HLA-E:NKG2A interaction and boost the ability of NK cells to kill cancer cells—without affecting other healthy immune cells. In mouse models of myeloma, treatment with 4D7 and human NK cells led to slower tumor growth. This more targeted approach could offer a safer and more effective way to activate the immune system against multiple myeloma and possibly other cancers.

 

 

"NKG2D-mediated cytotoxicity of CD4 cytotoxic T cells in multiple myeloma"

Source

Sojeong Kim, Jeong-Eun Kwak, June-Young Koh, Ji Eun Lee, Hye Won Kook, Minchae Kim, Haerim Chung, Yu Ri Kim, Soo Jeong Kim, Jin Seok Kim, June-Won Cheong, Min Goo Lee, Hoyoung Lee, Su-Hyung Park, Eui-Cheol Shin, Saeam Shin, Sun Och Yoon, Il-Kyu Choi, Jeong Seok Lee, Hyunsoo Cho; NKG2D-mediated cytotoxicity of CD4 cytotoxic T cells in multiple myeloma. Blood 2025; 146 (4): 456–470. doi: https://doi.org/10.1182/blood.2024025875 July 24, 2025.  

Overview

New research shows that a specific group of immune cells, called CD4+ cytotoxic T lymphocytes (CTLs), may play a direct role in killing myeloma cells and improving patient outcomes. These cells are a type of CD4+ T cell, which are usually known for helping other immune cells do their jobs. However, in this study, scientists discovered that some CD4+ T cells can directly attack and destroy cancer cells in multiple myeloma.

Using advanced techniques to study individual cells from the bone marrow of patients, researchers found that CD4+ CTLs were more common and more active in people with myeloma compared to earlier stages of the disease. These cells used a protein called NKG2D to recognize and kill myeloma cells. When this protein was blocked, the cancer-fighting ability of the CD4+ CTLs stopped. Patients with higher levels of NKG2D+ CD4+ CTLs had better survival outcomes, suggesting that boosting this specific immune response could lead to new and more effective immunotherapy treatments for multiple myeloma.

 

"Cytolytic helper T cells: a new addition to myeloma immunity"

Source

Tom Cupedo; Cytolytic helper T cells: a new addition to myeloma immunity. Blood 2025; 146 (4): 402–403. doi: https://doi.org/10.1182/blood.2025028916  July 24, 2025  

Overview

In this commentary, researchers highlight an exciting new discovery: a type of CD4+ T cell in the bone marrow of people with multiple myeloma that can directly recognize and kill myeloma cells. While CD8+ T cells have been the main focus of most immunotherapy studies, this research by Kim and colleagues brings attention to a smaller, less-studied group—CD4+ T-helper cells. Using advanced single-cell RNA sequencing, the team found a subpopulation of these helper cells with a cytotoxic (cell-killing) profile. These cytolytic CD4+ T cells, which have a Th1-like identity, were more common in patients with myeloma and its precursor stages, like MGUS and smoldering myeloma, than in healthy controls. Their presence was linked to better outcomes, especially in patients not eligible for stem cell transplant.

The study also showed that these cytolytic T-helper cells use a molecule called NKG2D to recognize and destroy myeloma cells. When this molecule was blocked, the cancer-killing ability of the cells was reduced. Importantly, these T cells appear to target the myeloma cells directly, rather than reacting to viral infections or other non-cancer signals. This suggests that they could be a powerful, untapped part of the immune response to multiple myeloma. The findings highlight the need to explore this underappreciated T-cell population further and rethink how we design immunotherapies. Adding cytolytic CD4+ T-helper cells to the mix could improve current treatments and help more patients fight their disease.

 

 

"Meta-analysis of the prognostic efficacy of daratumumab combined with standard therapy in high-risk multiple myeloma"

Source

Zhou, H., Zhang, M., Jin, Y., & Lang, X. (2025). Meta-analysis of the prognostic efficacy of daratumumab combined with standard therapy in high-risk multiple myeloma. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2532893 July 24, 2025.  

Overview

This study looked at how well Darzalex® (daratumumab, or DAR), when added to standard therapy, works for people with high-risk multiple myeloma. Researchers reviewed data from 11 different studies, covering nearly 5,000 patients. They compared those who received standard treatment alone to those who received standard treatment plus DAR. The goal was to see whether adding DAR improved outcomes like response to treatment, how long patients stayed in remission, and overall survival.

The results showed that patients who received DAR had better outcomes across the board. They were more likely to respond to treatment and lived longer without their disease getting worse. Overall survival was also improved. While anemia was less common in the DAR group, they were slightly more likely to experience low platelet and white blood cell counts. Still, the side effects were considered manageable. These findings support the use of DAR in combination with standard therapy as an effective treatment option for people with high-risk multiple myeloma.

 

 

"Recommended Phase II Doses of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma From MonumenTAL-1: Clinical Pharmacology Results"

Source

Gong, J., Zhou, J., Yuan, D., Ma, X., Vishwamitra, D., Hilder, B., Masterson, T.J., Tolbert, J., Renaud, T., Heuck, C., Kane, C., Samtani, M.N., Girgis, S., Haddish-Berhane, N., Berdeja, J., Krishnan, A. and Ouellet, D. (2025), Recommended Phase II Doses of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma From MonumenTAL-1: Clinical Pharmacology Results. Clin Pharmacol Ther. https://doi.org/10.1002/cpt.70004  July 24, 2025   

Overview

Talvey® (talquetamab) is the first approved bispecific antibody that targets both GPRC5D and CD3, offering a new treatment option for people with relapsed or refractory multiple myeloma (RRMM). In the MonumenTAL-1 study, more than 66% of patients responded to subcutaneous talquetamab given at either 0.4 mg/kg weekly or 0.8 mg/kg every other week—doses chosen for Phase II testing. Researchers looked closely at how the drug behaves in the body, how the immune system responds to it, and how well it works and is tolerated at different levels.

They found that the drug stayed in the body long enough to keep attacking the cancer cells, and higher doses led to stronger immune activity. Over time, talquetamab cleared from the body more slowly, allowing for more stable levels with ongoing treatment. Some patients—those with IgG myeloma or more advanced disease—cleared the drug faster, but they didn’t need dose adjustments. The study also showed that increasing the dose didn’t significantly boost treatment response, though it was linked to more mild taste changes (dysgeusia). Importantly, the body’s immune response to the drug didn’t reduce its effectiveness or safety. These results support the current dosing schedule for talquetamab and confirm its role as a promising option for treating RRMM.

 

 

"Real-world patient profile and step-up dosing process of early initiators of teclistamab for multiple myeloma in US hospitals: An analysis using the Premier Healthcare Database"

Source

Rose Tan C, Chinaeke E, Kim N, Lin D, Hester L, Fowler J, Gifkins D, Walker S, Fu AZ, Wu B. Real-world patient profile and step-up dosing process of early initiators of teclistamab for multiple myeloma in US hospitals: An analysis using the Premier Healthcare Database. J Manag Care Spec Pharm. 2025 Aug;31(8):772-781. doi: 10.18553/jmcp.2025.31.8.772.  July 24, 2025. 

Overview

Tecvayli® (teclistamab) is the first bispecific antibody of its kind approved in the U.S. for treating relapsed or refractory multiple myeloma. After its approval, many hospitals began giving the drug using a step-up dosing (SUD) approach to lower the risk of side effects. This real-world study looked at patients who started teclistamab in hospital settings during its first year on the market. Researchers wanted to understand who these patients were, how long they stayed in the hospital, and how often they experienced cytokine release syndrome (CRS), a known side effect of this type of therapy.

The study included 413 patients with a median age of 69, most of whom had other health issues such as anemia or kidney problems. Nearly all were treated in large, urban, teaching hospitals. Among the 302 patients who completed the SUD schedule, most stayed in the hospital for just under nine days and were able to finish treatment in one admission. About one-third experienced CRS, but most cases were mild. Symptoms like fever and low blood pressure were the most common, and supportive medications like dexamethasone, acetaminophen, and diphenhydramine were widely used. Tocilizumab, a drug used to treat CRS, was given to about 30% of patients. Overall, the study shows that teclistamab can be safely started in the hospital, even for older adults with other health concerns, with side effects that are generally manageable.

 

 

"Flow Cytometry in the Diagnosis and Prognosis of Multiple Myeloma"

Source

Adam Seegmiller, Flow Cytometry in the Diagnosis and Prognosis of Multiple Myeloma, Seminars in Diagnostic Pathology, 2025, 150942, ISSN 0740-2570, https://doi.org/10.1016/j.semdp.2025.150942. July 25, 2025 

Overview

Flow cytometry is a powerful tool used to diagnose and monitor plasma cell cancers like multiple myeloma. This review explains how it helps identify and study plasma cells by looking at specific markers on their surface. By comparing the typical features of healthy plasma cells to those of cancerous ones, doctors can tell the difference and gain important information about the disease.

The review also explores how certain unusual patterns found in cancerous plasma cells can help predict how the disease will behave. In addition, it highlights how flow cytometry is used after treatment to look for tiny amounts of disease that may remain—known as measurable residual disease (MRD). Detecting MRD through flow cytometry gives doctors a clearer picture of treatment success and helps guide future care.

 

 

"Comparison of outcomes with elranatamab and real world treatments in the UK for triple class exposed relapsed and refractory multiple myeloma"

Source

Tsang, C., O’Reilly, J.E., Carpenter, L. et al. Comparison of outcomes with elranatamab and real world treatments in the UK for triple class exposed relapsed and refractory multiple myeloma. BMC Cancer 25, 1219 (2025). https://doi.org/10.1186/s12885-025-14624-9  July 25, 2025. 

Overview

Patients with triple-class exposed (TCE), relapsed and refractory multiple myeloma (RRMM) face limited treatment options and poor outcomes. Elranatamab is a new investigational therapy that targets BCMA and has shown promising results in a clinical trial called MagnetisMM-3. This study looked at how patients treated with elranatamab compared to similar patients treated in the UK’s National Health Service (NHS) with standard therapies between 2015 and 2023.

Researchers compared survival outcomes from 81 NHS patients who received various real-world treatments—including pomalidomide plus dexamethasone—to those of patients in the MagnetisMM-3 trial. The NHS group had a median progression-free survival (PFS) of just under 4 months and a median overall survival (OS) of 11 months. In contrast, patients who received elranatamab had significantly longer PFS in both unadjusted and adjusted analyses. While results for OS were mixed after adjustments, the findings suggest elranatamab may offer improved disease control for this hard-to-treat group of myeloma patients.

 

 

"Vaccination in Multiple Myeloma: Challenges and Strategies"

Source

E. A. Martino, E. Vigna, A. Bruzzese, et al., “Vaccination in Multiple Myeloma: Challenges and Strategies,” European Journal of Haematology (2025): 1–10, https://doi.org/10.1111/ejh.70013. July 26, 2025.  

Overview

People with multiple myeloma have weakened immune systems because of both the disease itself and the treatments they receive. This puts them at high risk for serious infections. Vaccines are important for protecting against these infections, but patients with myeloma often have weaker responses to standard vaccines. This review looked at how well different vaccines work in people with myeloma and what factors influence their effectiveness.

Even though vaccine responses may be reduced, studies show that vaccines for flu, pneumonia, and COVID-19 still help lower the risk of infection and hospital stays. For example, using a two-step pneumonia vaccine schedule and following a three-dose vaccine plan after stem cell transplant can help protect against serious illness. COVID-19 vaccine response is lower in patients on certain treatments like anti-CD38 or BCMA-targeted therapies, so booster shots and preventive antibodies may be needed. Vaccines for shingles, hepatitis B, and Hib are also recommended. Blood tests that measure immune cell levels can help guide vaccine planning. Overall, vaccines remain a key part of care for myeloma patients, and tailoring the approach to each patient can improve outcomes.

 

 

"Fractures incidence and its association on mortality in multiple myeloma patients: a nationwide cohort study (CAREMM-2105 study)"

Source

Ha, J., Choi, S., Park, SS. et al. Fractures incidence and its association on mortality in multiple myeloma patients: a nationwide cohort study (CAREMM-2105 study). Sci Rep 15, 27321 (2025). https://doi.org/10.1038/s41598-025-09811-4  July 27, 2025   

Overview

People with multiple myeloma often have weakened bones, which raises their risk of fractures. These fractures can lower quality of life and increase the risk of death. This study used data from Korea’s National Health Insurance to compare fracture rates in over 9,000 myeloma patients and a matched group from the general population. The results showed that people with myeloma had significantly more fractures—especially in the spine and hip—compared to those without the disease.

The study also found that having a fracture within the first year after a myeloma diagnosis increases the risk of death. Hip fractures were especially serious, doubling the risk of mortality. These findings highlight the need to closely monitor bone health in people with multiple myeloma and take steps to prevent fractures early in the disease. Doing so may help improve both quality of life and survival.

 

 

"LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy"

Source

Li, Z., Liu, R., Fang, Z. et al. LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy. Oncogene (2025). https://doi.org/10.1038/s41388-025-03513-x  July 28, 2025   

Overview

Multiple myeloma is a blood cancer that still lacks highly effective targeted treatments. A key protein called IRF4 helps myeloma cells grow and survive, but how this protein is regulated in the body hasn’t been fully understood. This study found that another protein, LAMP5, plays an important role in protecting IRF4 from being broken down by the body’s waste-removal system. LAMP5 also helps move IRF4 into the cell’s nucleus, where it can activate another cancer-promoting protein called c-MYC. In turn, c-MYC increases the production of LAMP5, creating a harmful cycle that drives myeloma progression.

Researchers identified a drug called pyrazofurin that can break this cycle by blocking the interaction between LAMP5 and IRF4. This causes IRF4 to be degraded, slowing down the growth of myeloma cells. These findings offer new insight into how myeloma progresses and point to a promising treatment strategy that targets this newly discovered pathway.

 

 

"High glutamate levels in the bone marrow of multiple myeloma patients promote osteoclast formation: a novel target for osteolytic bone disease"

Source

Toscani, D., Lungu, O., Chiu, M. et al. High glutamate levels in the bone marrow of multiple myeloma patients promote osteoclast formation: a novel target for osteolytic bone disease. Leukemia (2025). https://doi.org/10.1038/s41375-025-02715-2  July 28, 2025. 

Overview

Multiple myeloma is a cancer that depends heavily on glutamine, a type of amino acid. Because of this, the bone marrow environment in people with myeloma has lower levels of glutamine and higher levels of another substance called glutamate. This imbalance is known to block the formation of new bone-building cells, but until now, its effect on bone-resorbing cells called osteoclasts wasn’t fully understood.

This study found that bone marrow cells from myeloma patients release more glutamate than those from people with earlier-stage conditions like MGUS or smoldering myeloma. This rise in glutamate is linked to more active bone breakdown. Researchers discovered that glutamate helps osteoclasts grow by activating certain cell pathways, especially in early disease stages when glutamate levels are still low. However, in active myeloma where glutamate is already high, this effect doesn’t increase further. They also found that blocking a specific glutamate transporter (EAAT1) stops the formation of osteoclasts. These findings suggest that targeting glutamate transport could be a new way to help prevent bone damage in people with multiple myeloma.

 

 

"Practical Guidance on Clinical Management of Belantamab Mafodotin-Associated Ocular Events"

Source

E. Terpos, S. Trudel, M.-V. Mateos, et al., “Practical Guidance on Clinical Management of Belantamab Mafodotin-Associated Ocular Events,” American Journal of Hematology (2025): 1–12, https://doi.org/10.1002/ajh.70015.  July 28, 2025.  

Overview

Blenrep (belantamab mafodotin, or belamaf) is an effective treatment for people with relapsed or hard-to-treat multiple myeloma. However, a common side effect of this drug is eye problems, especially changes to the surface of the cornea. These side effects are usually mild to moderate and reversible, but they require careful management. A team of blood cancer and eye specialists reviewed data from clinical trials, real-world use, and published studies to create clear guidelines on how to identify, monitor, and manage these ocular issues during belamaf treatment.

The experts recommend that all patients get an eye exam before starting belamaf, and again before each of the first three treatment cycles. If there’s a delay in scheduling the first eye exam and the patient’s myeloma is worsening, treatment can start while waiting for the exam. Eye drops such as artificial tears and adjusting the belamaf dose or timing can help manage side effects. These changes don’t reduce how well the treatment works. After the fourth cycle, doctors can use a short vision questionnaire and their clinical judgment to decide on further dosing or the need for an eye specialist visit. These expert recommendations aim to make belamaf easier to use and improve the experience and outcomes for patients.

 

 

"Real-World Treatment Patterns and Outcomes in Patients With Relapsed/Refractory Multiple Myeloma and 1–3 Prior Lines of Therapy: Optum Database"

Source

B. Dhakal, H. Einsele, J. M. Schecter, et al., “Real-World Treatment Patterns and Outcomes in Patients With Relapsed/Refractory Multiple Myeloma and 1–3 Prior Lines of Therapy: Optum Database,” Cancer Medicine 14, no. 15 (2025): e71093, https://doi.org/10.1002/cam4.71093.  July 28, 2025.   

Overview

As more people with multiple myeloma are treated early and often with Revlimid® (lenalidomide), a growing number of patients become resistant to it. This study looked at real-world data to better understand how these patients are being treated, how often they use health care resources, and what their outcomes are like. Researchers used two large U.S. databases that tracked patients between 2016 and 2022. All patients included in the analysis had already received one to three previous lines of therapy, including a proteasome inhibitor, and were now considered lenalidomide-refractory.

The study included over 1,300 patients from one database and nearly 1,600 from another. Most patients were in their late 60s or early 70s and had multiple other health conditions. The most common drug combinations included daratumumab, pomalidomide, bortezomib, and dexamethasone. Unfortunately, treatment options became less effective as patients went through more lines of therapy. By the sixth line of treatment, over 95% of patients had either died or stopped treatment. On average, patients moved to a new treatment within 5 to 6 months, and their overall survival ranged from about 35 to 41 months. These findings show that people with lenalidomide-refractory multiple myeloma have poor outcomes and highlight the urgent need for more effective treatment options.

 

 

"ATF4:p52 complex activates oncogenic enhancers in multiple myeloma via p300/CBP recruitment to regulate BACH1"

Source

Daniel Aron Ang, Nathan Harmston, Yinghui Li, ATF4:p52 complex activates oncogenic enhancers in multiple myeloma via p300/CBP recruitment to regulate BACH1, Cancer Letters, Volume 623, 2025, 217727, ISSN 0304-3835, https://doi.org/10.1016/j.canlet.2025.217727. July 28, 2025. 

Overview

Some patients with multiple myeloma (MM) have a more aggressive form of the disease, often linked to a constantly active cell signaling pathway called the non-canonical NF-κB (ncNF-κB) pathway. A key player in this pathway is a protein called p52, which helps control certain parts of the genome known as enhancers—regions that turn genes on or off. Previous research showed that p52 boosts cancer-driving gene activity in MM, but how it does this wasn’t fully understood.

In this study, researchers looked closely at MM cells from both lab models and patient samples. They discovered that p52 teams up with another protein called ATF4 to control a set of powerful enhancers linked to MM. This duo brings in other molecules, called histone acetyltransferases (p300 and CBP), that help switch on genes involved in cancer growth. One of the key genes turned on by this complex is BACH1, which was found near a super-enhancer—a strong genetic switch—and drives MM cells to grow and divide. These findings help explain how changes in gene control may contribute to MM progression and suggest new targets for treatment

 

 

"Quality of Patient-Reported Outcomes in Multiple Myeloma Randomized Controlled Trial Protocols and Publications According to the SPIRIT-PRO and CONSORT-PRO guidelines: A Systematic Review"

Source

D. Shah, F. Sparano, V. Shah, et al., “Quality of Patient-Reported Outcomes in Multiple Myeloma Randomized Controlled Trial Protocols and Publications According to the SPIRIT-PRO and CONSORT-PRO guidelines: A Systematic Review,” European Journal of Haematology (2025): 1–11, https://doi.org/10.1111/ejh.70002.  July 29, 2025. 

Overview

Patient-reported outcomes (PROs)—how patients feel and function during treatment—are playing a growing role in multiple myeloma (MM) clinical trials. These insights can help doctors make better treatment decisions. But even though PROs are being included more often, the quality of how they’re planned and reported in clinical trial protocols is often not up to international standards.

In this study, researchers reviewed MM randomized controlled trials (RCTs) from 2014 to 2023 that used a common PRO questionnaire called the EORTC QLQ-C30. They looked at how well the trials followed guidelines for including and reporting PROs. Out of 35 trials with over 20,000 patients, about 70% had publicly available protocols. On average, these protocols followed about half of the recommended standards. Most did a good job explaining why certain PRO measures were used and when they were collected. However, many lacked important details like how to prevent missing data or how PROs would be monitored during the trial.

When it came to reporting results, most trials clearly explained their methods and statistical findings. But fewer than two-thirds included key PRO-related details, such as what they were trying to measure or how they gathered patient responses. Only 11% of trials stated a clear hypothesis for PROs. Interestingly, trials that had a separate publication focused on PROs or found statistically significant PRO differences were more likely to report higher quality PRO data, raising concerns about possible reporting bias.

Overall, while some progress has been made, many MM trials still fall short in how they plan and report PROs. Improving this could lead to better data and a clearer understanding of how treatments affect patients’ quality of life. The study highlights the need for stronger protocol design from the start, especially to reduce missing patient data, which can distort results.

 

 

"Early daratumumab-based therapy demonstrates significant effectiveness in patients with relapsed and refractory multiple myeloma: a real-world retrospective investigation"

Source

Chen, Y., Cai, Q., Qiu, Z., Geng, H., Li, Y., Zhan, R., & Zheng, Z. (2025). Early daratumumab-based therapy demonstrates significant effectiveness in patients with relapsed and refractory multiple myeloma: a real-world retrospective investigation. Journal of Chemotherapy, 1–10. https://doi.org/10.1080/1120009X.2025.2540172  July 29, 2025. 

Overview

This study looked at how well Darzalex® (daratumumab) works for patients with relapsed and refractory multiple myeloma (RRMM) in real-world settings, not just in clinical trials. Researchers reviewed the records of 62 patients treated at Union Hospital of Fujian Medical University between 2018 and 2024. Most of these patients had only received one prior line of treatment before starting daratumumab. On average, they were treated with daratumumab for about 7.5 cycles and followed for a little over 16 months.

Among the 56 patients who could be evaluated, nearly 90% responded to treatment. About 20% reached a stringent complete response, and another 23% had a complete response. The median progression-free survival (PFS)—how long patients lived without the disease getting worse—was 25.2 months. One year after treatment, 75% of patients were still progression-free; after three years, that number dropped to 25%. The median overall survival (OS) was 42.7 months, with 84% of patients alive at one year and 63% at three years. However, patients with poorer general health did not do as well. Overall, these results suggest that starting daratumumab earlier in treatment may lead to better outcomes for RRMM patients, but more research is needed to confirm these findings.

 

 

"Assessing frailty in patients with relapsed/refractory multiple myeloma: A comparison between the patient-reported frailty phenotype and the International Myeloma Working Group frailty index"

Source

Daniela Krepper, Francesco Sparano, Johannes M. Giesinger, Gianluca Gaidano, Pasquale Niscola, Katia Codeluppi, Elisabetta Antonioli, Catello Califano, Lajos Floro, Ombretta Annibali, Claudio Fozza, Agostino Tafuri, Patrizio Mazza, Leonardo Potenza, Marco Vignetti, Michele Cavo, Maria Teresa Petrucci, Fabio Efficace, Assessing frailty in patients with relapsed/refractory multiple myeloma: A comparison between the patient-reported frailty phenotype and the International Myeloma Working Group frailty index, Journal of Geriatric Oncology, Volume 16, Issue 6, 2025, 102266, ISSN 1879-4068, https://doi.org/10.1016/j.jgo.2025.102266. July 2025. 

Overview

This study looked at a new way to measure frailty in people with relapsed or refractory multiple myeloma (RRMM) using patient-reported outcomes. Frailty is an important factor in treatment planning, and the International Myeloma Working Group Frailty Index (IMWG FI) is commonly used for this. However, a newer tool—the Patient-Reported Frailty Phenotype (PRFP)—was recently proposed to better capture how patients feel and function in real life. Researchers used data from over 500 adults with RRMM to test how well this new tool worked and to explore how frailty levels relate to quality of life.

The results showed that the new PRFP tool classified about 25% of patients as frail, similar to the IMWG FI. However, the agreement between the two tools was only fair, suggesting they may measure frailty in different ways. Patients labeled as frail using the PRFP reported more side effects, more symptoms, and poorer outlooks compared to patients who were pre-frail or fit. This suggests that the PRFP may offer important insights into patients’ day-to-day experience with RRMM. More research is needed, but this patient-centered tool could help doctors better understand frailty and tailor treatments more effectively.

 

 

"A Cure, a Cure, My Kingdom for a Cure…"

Source

Sagar Lonial et al. A Cure, a Cure, My Kingdom for a Cure…. JCO 0, JCO-25-01258 DOI:10.1200/JCO-25-01258 July 29. 2025. 

Overview

For years, a true cure for multiple myeloma has felt just out of reach. While some patients have achieved long-term remissions—particularly those treated with intensive protocols or stem cell transplants—only about 10% to 15% remained free of disease a decade later. But new data from the CARTITUDE-1 trial offer a hopeful shift. In this study, nearly one-third of patients who received cilta-cel CAR T-cell therapy—after failing at least five prior treatments—remained in remission after five years. Some patients were still MRD-negative with no treatment and clear scans, a strong signal that cure might be possible, even in advanced cases. These results suggest that using immune-based therapies earlier in treatment might increase the number of patients who can achieve what researchers call a “functional cure”—meaning the disease is no longer active or life-limiting, even if it’s not completely gone at the molecular level.

Still, many questions remain. How long does remission need to last before we can confidently call it a cure? What role do MRD testing and immune recovery play in making that determination? Experts believe that a minimum of five to ten years off therapy with deep, sustained MRD negativity may be a realistic benchmark, but long-term follow-up is needed. While newer treatments like CAR T-cells and bispecific antibodies are showing unprecedented depth of response, researchers caution against scaling back therapy too soon. The path to curing more patients will likely involve careful combinations of therapies, a better understanding of immune recovery, and a strong commitment to long-term data collection. Cure may not be guaranteed for most patients yet, but it's no longer just a dream.

 

 

"Quantitative risk of underlying disease conditions for progression from monoclonal gammopathy to multiple myeloma: a nationwide cohort study"

Source

H. Ko, S. Choi, S.-S. Park, S. Jung, C.H. Lee, S. Han, C.-K. Min, Quantitative risk of underlying disease conditions for progression from monoclonal gammopathy to multiple myeloma: a nationwide cohort study, ESMO Open, Volume 10, Issue 7, 2025, 105327, ISSN 2059-7029, https://doi.org/10.1016/j.esmoop.2025.105327. July 2025. 

Overview

Researchers in South Korea studied how certain health conditions might help predict which patients with monoclonal gammopathy of undetermined significance (MGUS) are more likely to develop symptomatic multiple myeloma (MM). Using a large national health database that covers almost the entire Korean population, they followed 5,361 people with MGUS. Of those, 345 eventually developed MM, and 253 of them showed symptoms.

The study found that certain factors—being female, having chronic lung disease, diabetes, peptic ulcers, or a non-cancerous blood disorder—increased the risk of MGUS turning into symptomatic MM. Based on this, the researchers built a risk-scoring model that places patients into low-, intermediate-, or high-risk categories. Compared to the low-risk group, people in the high-risk group were over two and a half times more likely to develop symptomatic MM.

This model could be a useful tool for doctors, helping them spot high-risk patients earlier and focus more attention and monitoring on those who need it most.

 

 

"Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement"

Source

Steinhardt, M.J., Schaefers, C., Leypoldt, L.B. et al. Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement. Blood Cancer J. 15, 126 (2025). https://doi.org/10.1038/s41408-025-01330-9 July 30, 2025. 

Overview

Extramedullary multiple myeloma (EMD), which occurs outside the bone marrow, is difficult to treat and often leads to poor outcomes. While new treatments like CAR T cell therapy and bispecific antibodies (bsABs) have shown promise for relapsed myeloma, it's still unclear which option works best for EMD. In this study, researchers looked back at 80 patients with non-bone-adjacent EMD who were treated at three hospitals in Germany using one of four therapies: ide-cel, cilta-cel (both CAR T cell therapies), or teclistamab and talquetamab (both bsABs).

These patients had already been through many treatments—on average, five to seven prior lines of therapy—and many had high-risk genetic features. Most had never been treated with BCMA-targeted therapy before. The results showed that CAR T cell therapies had much higher response rates: 100% for cilta-cel and 82% for ide-cel, compared to only 29% and 36% for the bsABs. CAR T cells were also more likely to completely clear signs of EMD and led to longer remission times. For example, patients treated with cilta-cel hadn’t yet reached a median progression-free survival (PFS), while those treated with ide-cel had a PFS of 7.3 months. In contrast, patients on bsABs had shorter PFS—4.0 months for talquetamab and 2.6 months for teclistamab.

The study also found that patients who received debulking therapy—treatment to shrink tumors before CAR T cells—had better outcomes, especially if the debulking worked. However, EMD in the organs or soft tissue responded less often than EMD in other areas. Overall, the data suggest that CAR T cell therapy offers stronger, longer-lasting responses for patients with EMD compared to bispecific antibodies.

 

 

"Outcomes following different upfront stem cell transplantation strategies for multiple myeloma: a statistical perspective on behalf of the Chronic Malignancies Working Party of the EBMT"

Source

Iacobelli, S., Schönland, S., Koster, L. et al. Outcomes following different upfront stem cell transplantation strategies for multiple myeloma: a statistical perspective on behalf of the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02675-2 July 30, 2025.  

Overview

Multiple myeloma (MM) is a complex and often aggressive cancer. New treatments like bispecific antibodies and CAR T cells have helped improve response rates and survival, but most patients still experience a relapse. For those eligible, high-dose chemotherapy followed by autologous stem cell transplant (auto-HCT) remains a standard treatment. While most patients get a single auto-HCT, there has been ongoing debate about whether a planned second transplant—either another auto-HCT (tandem) or an allogeneic transplant after the first (auto-allo)—offers better long-term results.

This study analyzed outcomes from nearly 25,000 MM patients aged 20 to 65 who had their first auto-HCT between 2002 and 2015. Of those, about 3,700 received a tandem auto-HCT and nearly 900 received an auto-allo-HCT. Using advanced statistical models to track how outcomes changed over time, researchers found that tandem transplants gave a small but consistent survival benefit compared to a single transplant. However, the biggest long-term gains were seen in patients who had an auto-allo transplant, despite a higher risk of early death. These results suggest that while all three strategies have value, auto-allo-HCT may offer the best long-term survival for some patients, if they can handle the early risks.

 

 

"Closing the gaps: Tackling myeloma inequities in Latin America"

Source

Jorge Contreras, Closing the gaps: Tackling myeloma inequities in Latin America, Hematology, Transfusion and Cell Therapy, Volume 47, Issue 3, 2025, 103848, ISSN 2531-1379, https://doi.org/10.1016/j.htct.2025.103848. July-September 2025. 

Overview

Multiple myeloma (MM) remains a major global health issue, with survival rates improving thanks to new treatments. However, in Latin America, serious gaps in care continue to affect patient outcomes. Compared to wealthier countries, patients in this region are more likely to be diagnosed at a late stage, especially among Indigenous and underserved communities. This is largely due to limited awareness, weak screening programs, and structural healthcare inequities.

Social and economic factors—like income, education, and where a person lives—play a big role in how early MM is diagnosed and how well it is treated. People in rural or low-income areas often face long delays in diagnosis, poor access to specialists, and limited treatment options. Healthcare systems in many Latin American countries are fragmented, with major differences between public and private care. Many public clinics and hospitals don’t have access to essential diagnostic tools or advanced treatments like autologous stem cell transplants or proteasome inhibitors.

Cost is another big problem. Newer MM treatments are expensive, and many patients can’t afford them due to weak insurance coverage. As a result, some patients either receive lower-quality care or skip treatment entirely. On top of that, delays in referrals, poor infrastructure, and long wait times make it even harder for patients to get timely care, all of which worsens their chances of survival.

To improve MM outcomes in Latin America, targeted action is needed. This includes investing in healthcare infrastructure, expanding access to affordable treatments, and addressing the social factors that affect health. Governments, NGOs, and international partners must work together to close these gaps. Community involvement is also key. Local awareness campaigns and the use of community health workers can help reach underserved populations and encourage early diagnosis and consistent care.

More research focused on Latin America is also essential. Regional MM registries can help track treatment outcomes and highlight where interventions are most needed. Overall, the letter stresses that tackling health disparities in MM will require policy change, stronger healthcare systems, and a clear commitment to equity—so that all patients, regardless of background, can benefit from advances in care

 

 

"Advanced quantification pipeline reveals new spatial and temporal tumor characteristics in preclinical multiple myeloma"

Source

Sun, Z., Godbe, J.M., Zheleznyak, A. et al. Advanced quantification pipeline reveals new spatial and temporal tumor characteristics in preclinical multiple myeloma. EJNMMI Res 15, 95 (2025). https://doi.org/10.1186/s13550-025-01291-x July 31, 2025. 

Overview

Imaging is a key tool in studying multiple myeloma (MM), especially in tracking how the disease spreads in the bones over time. But when researchers use PET/CT scans in small animal studies, analyzing those images by hand is tricky. Human error, artifacts from normal body functions, and movement between scans can make the results unreliable. To solve this, researchers created a semi-automated system that can more accurately measure tumor activity in mice with MM.

This new system focuses on specific bone areas where MM usually appears—like the spine, pelvis, femurs, and sacrum. Using a type of artificial intelligence called Attention U-Net, the system was trained to identify and segment these bone areas on CT images. It also used custom algorithms to clean up signals from things like bladder or bowel activity and track tumor growth along the skeleton.

The results were impressive. The tool picked up early signs of MM spreading to bones, especially near joints. By day 18 after tumor cells were implanted, significant increases in tumor signals were detected in multiple bones. The system also revealed differences between male and female mice. Female mice showed more bone damage near the hips at later stages of the disease.

Overall, this new pipeline gives researchers a more accurate and consistent way to study how MM grows in bones and responds to treatment. It reduces errors, saves time, and helps reveal patterns—like joint-specific tumor spread and sex-based bone loss—that could improve how we study and treat bone-involved cancers.

 

 

"NSUN2-mediated RNA m5C modification drives multiple myeloma progression by enhancing the stability of HIP1 mRNA"

Source

Jiang, Y., Sun, J., Chen, Y. et al. NSUN2-mediated RNA m5C modification drives multiple myeloma progression by enhancing the stability of HIP1 mRNA. Sci Rep 15, 27888 (2025). https://doi.org/10.1038/s41598-025-13695-9  July 31, 2025. 

Overview

Researchers are learning more about how certain genetic changes affect multiple myeloma (MM), and one of those changes involves a type of RNA modification called 5-methylcytosine (m5C). This modification plays an important role in how genes are regulated. In this study, scientists focused on an enzyme called NSUN2, which adds m5C to RNA, to see how it might affect MM.

They found that NSUN2 levels were much higher in patients with MM, and those with more NSUN2 had worse outcomes. These patients also showed higher overall levels of m5C in their RNA. When researchers blocked NSUN2 in lab experiments, it reduced m5C levels, slowed down cancer cell growth, triggered cell death, and even shrank tumors in animal models.

Digging deeper, the team used special tests to find out which genes were being affected by NSUN2. They discovered that NSUN2 boosts the activity of a gene called HIP1 by stabilizing its RNA. When NSUN2 was blocked, HIP1 levels dropped—but if HIP1 was added back, the tumor cells kept growing, even without NSUN2. This showed that HIP1 plays a key role in how NSUN2 drives MM growth.

Overall, the study highlights NSUN2 as a potential warning sign for aggressive MM and a possible target for future treatments. Blocking NSUN2 could be a new way to slow down or stop the disease.

 

 

"A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up"

Source

Sherilyn A. Tuazon, Andrew J. Portuguese, Margot J. Pont, Andrew J. Cowan, Gabriel O. Cole, Blythe D. Sather, Xiaoling Song, Sushma Thomas, Brent L. Wood, Michelle Blake, Melissa G. Works, Mazyar Shadman, Emily C. Liang, Qian V. Wu, Jenna M. Voutsinas, Ted A. Gooley, Cameron J. Turtle, Brian G. Till, David G. Coffey, David G. Maloney, Stanley R. Riddell, Damian J. Green; A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up. Blood 2025; 146 (5): 535–545. doi: https://doi.org/10.1182/blood.2024027681  July 31, 2025. 

Overview

FCARH143 is a type of CAR T-cell therapy designed to target BCMA, a protein found on multiple myeloma (MM) cells. In a phase 1 clinical trial, it was tested in patients with relapsed or hard-to-treat MM—people who had already been through many rounds of treatment without success. Most had gone through a median of eight prior therapies, and nearly half had disease outside the bone marrow.

The treatment involved collecting each patient’s T cells, engineering them to recognize BCMA, and then infusing them back after chemotherapy to weaken the immune system. Doses ranged from 50 to 450 million CAR T cells. Of the 28 patients enrolled, 25 went on to receive the therapy. Side effects included cytokine release syndrome in 84% of patients—mostly mild—and some neurotoxicity, but there were no treatment-related deaths.

The results were impressive. Every treated patient responded to the therapy, and 64% achieved a stringent complete response, meaning no signs of disease. The median time before the cancer started to grow again (progression-free survival) was 15.5 months, and overall survival was 32.1 months. Even when including all patients originally enrolled in the study, the response rate was still very high at nearly 90%.

Overall, FCARH143 showed powerful anti-myeloma effects and manageable side effects, even in patients with high-risk features. These results support moving forward with more studies in patients with aggressive, treatment-resistant multiple myeloma.

 

 

"Time-tested safety: FCARH143’s 5-year myeloma journey"

Source

Samer Al Hadidi; Time-tested safety: FCARH143’s 5-year myeloma journey. Blood 2025; 146 (5): 519–520. doi: https://doi.org/10.1182/blood.2025029157 July 31, 2025  

Overview

This commentary looks at new long-term results from a phase 1 trial of FCARH143, a fully human BCMA-targeted CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM). The therapy showed a 100% overall response rate in heavily pretreated patients, with 68% achieving a stringent complete response. Patients in the study had already been through a median of eight treatments, and many had high-risk disease, including extramedullary disease (EMD). Even in this tough population, FCARH143 showed strong, lasting responses with a median progression-free survival of 15.5 months and overall survival of 32 months.

What makes FCARH143 stand out is its fully human design, which may reduce immune rejection and improve how long the CAR T cells last in the body. The therapy uses a balanced mix of helper (CD4+) and killer (CD8+) T cells and includes a modified EGFR marker to help track the cells after they’re infused. This marker also allows doctors to potentially shut down the cells if serious side effects occur.

The treatment was generally well tolerated. Most patients experienced mild to moderate cytokine release syndrome (CRS), with just one case of grade 3 severity and no grade 4 or 5 events. Neurotoxicity was also mild, with no serious or delayed effects. One patient developed Parkinson’s disease two years after treatment, but it wasn’t linked to the therapy. Another patient developed myelodysplastic syndrome nearly five years later, which raises the need for long-term monitoring for secondary cancers—something also noted in other CAR T trials.

Interestingly, the response didn’t seem to depend on the dose. Even patients who received the lowest dose of CAR T cells (50 million) had strong outcomes, which suggests this therapy may be more potent than others like ide-cel, where lower doses are less effective. However, patients with EMD still had worse outcomes than those without, which continues to be a challenge in the MM treatment landscape.

While the results are promising, the trial included only 25 patients at a single center, so larger studies are needed. It’s also unclear how FCARH143 will fit into the growing lineup of FDA-approved CAR T-cell therapies and bispecific antibodies. The trial didn’t define a maximum tolerated dose, but the authors suggest 450 million cells is a safe option moving forward.

Looking ahead, FCARH143 has some exciting features. The built-in EGFR safety switch could be useful in managing severe toxicities, and the fact that most patients received the therapy as outpatients could lower costs and improve the patient experience. The developers also plan to explore dual-target CAR T cells that go after both BCMA and GPRC5D, which could help prevent relapse caused by antigen loss.

In summary, FCARH143 shows strong long-term potential as a fully human CAR T-cell therapy for multiple myeloma. Its high response rates, manageable side effects, and manufacturing consistency make it a strong candidate for future development. Whether it outperforms currently approved therapies remains to be seen, but the results so far offer strong support for continuing research in this direction.

 

 

"Clonal hematopoiesis is clonally unrelated to multiple myeloma and is associated with specific microenvironmental changes"

Source

Marta Lionetti, Margherita Scopetti, Antonio Matera, Akihiro Maeda, Alessio Marella, Francesca Lazzaroni, Giancarlo Castellano, Sonia Fabris, Stefania Pioggia, Silvia Lonati, Alfredo Marchetti, Alessandra Cattaneo, Marta Tornese, Antonino Neri, Claudia Leoni, Loredana Pettine, Valentina Traini, Ilaria Silvestris, Marzia Barbieri, Giuseppina Fabbiano, Domenica Ronchetti, Elisa Taiana, Claudio De Magistris, Matteo C. Da Vià, Francesco Passamonti, Niccolò Bolli; Clonal hematopoiesis is clonally unrelated to multiple myeloma and is associated with specific microenvironmental changes. Blood 2025; 146 (5): 571–584. doi: https://doi.org/10.1182/blood.2024026236  July 31, 2025  

Overview

This commentary looks at new long-term results from a phase 1 trial of FCARH143, a fully human BCMA-targeted CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM). The therapy showed a 100% overall response rate in heavily pretreated patients, with 68% achieving a stringent complete response. Patients in the study had already been through a median of eight treatments, and many had high-risk disease, including extramedullary disease (EMD). Even in this tough population, FCARH143 showed strong, lasting responses with a median progression-free survival of 15.5 months and overall survival of 32 months.

What makes FCARH143 stand out is its fully human design, which may reduce immune rejection and improve how long the CAR T cells last in the body. The therapy uses a balanced mix of helper (CD4+) and killer (CD8+) T cells and includes a modified EGFR marker to help track the cells after they’re infused. This marker also allows doctors to potentially shut down the cells if serious side effects occur.

The treatment was generally well tolerated. Most patients experienced mild to moderate cytokine release syndrome (CRS), with just one case of grade 3 severity and no grade 4 or 5 events. Neurotoxicity was also mild, with no serious or delayed effects. One patient developed Parkinson’s disease two years after treatment, but it wasn’t linked to the therapy. Another patient developed myelodysplastic syndrome nearly five years later, which raises the need for long-term monitoring for secondary cancers—something also noted in other CAR T trials.

Interestingly, the response didn’t seem to depend on the dose. Even patients who received the lowest dose of CAR T cells (50 million) had strong outcomes, which suggests this therapy may be more potent than others like ide-cel, where lower doses are less effective. However, patients with EMD still had worse outcomes than those without, which continues to be a challenge in the MM treatment landscape.

While the results are promising, the trial included only 25 patients at a single center, so larger studies are needed. It’s also unclear how FCARH143 will fit into the growing lineup of FDA-approved CAR T-cell therapies and bispecific antibodies. The trial didn’t define a maximum tolerated dose, but the authors suggest 450 million cells is a safe option moving forward.

Looking ahead, FCARH143 has some exciting features. The built-in EGFR safety switch could be useful in managing severe toxicities, and the fact that most patients received the therapy as outpatients could lower costs and improve the patient experience. The developers also plan to explore dual-target CAR T cells that go after both BCMA and GPRC5D, which could help prevent relapse caused by antigen loss.

In summary, FCARH143 shows strong long-term potential as a fully human CAR T-cell therapy for multiple myeloma. Its high response rates, manageable side effects, and manufacturing consistency make it a strong candidate for future development. Whether it outperforms currently approved therapies remains to be seen, but the results so far offer strong support for continuing research in this direction.

 

 

"Finding the Right Time to Discuss Advance Care Planning with Myeloma Patients and Their Carers: An Opportunity for Nursing"

Source

Emma Matthews, Kate Montague-Hellen, Joanne Bird, Finding the Right Time to Discuss Advance Care Planning with Myeloma Patients and Their Carers: An Opportunity for Nursing, Seminars in Oncology Nursing, 2025, 151913, ISSN 0749-2081, https://doi.org/10.1016/j.soncn.2025.151913. July 31, 2025. 

Overview

As treatments for multiple myeloma improve, patients are living longer with the disease. But even with a focus on symptom relief and quality of life through palliative care and advance care planning (ACP), many people still think these services are only for the final stages of life. This misunderstanding leads to confusion about when these conversations should actually begin.

In this study, researchers interviewed 10 patients and 5 caregivers to better understand their experiences and preferences around ACP and end-of-life discussions. The analysis revealed three main themes: responsibility, receptivity, and resources. Many patients said ACP was never brought up, or wouldn’t have been, unless they or their caregiver raised the topic themselves. While both healthcare professionals and patients were seen as responsible for starting these conversations, most believed it should come from the medical team.

There was no single moment that felt universally right for everyone to start talking about palliative care—though most agreed it shouldn’t happen right at diagnosis. Instead, the right time depends on the person’s readiness and support systems. Resources—such as healthcare staff, community groups, or charities—also played a key role in helping patients and families feel prepared and supported.

In the end, the study shows that ACP conversations are often put off for too long. Patients and caregivers want doctors to take the lead, but also recognize that everyone’s timing and needs are different.

 

 

"The impact of age on survival and excess mortality after autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients"

Source

Mizuno S, Gras L, Baaij LG, Koster L, D’Souza A, Hari PN, Estrada-Merly N, Saber W, Cowan AJ, Iida M, Okamoto S, Takamatsu H, Kawamura K, Kodera Y, Hamad N, Ko B-S, Liam C, Ho KW, Goh AS, Keat TS, Elhaddad AM, Bazarbachi A, Chaudhry BQUN, Alfar R, Bekadja MA, Benakli M, Ortiz CAF, Riva E, Verburgh E, Galeano S, Bass F, Mian H, McCurdy A, Wang FR, Neumann D, Koh MBC, Snowden JA, Schönland S, McLornan DP, Hayden PJ, Balari AMS, Greinix HT, Aljurf M, Atsuta Y, Rondelli D, Niederwieser DW, Garderet L. The impact of age on survival and excess mortality after autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients. Haematologica; https://doi.org/10.3324/haematol.2025.288041 [Early view].  July 31, 2025. 

Overview

Even with new treatments available, autologous stem cell transplant (auto-HCT) is still the main approach for treating newly diagnosed multiple myeloma (MM). This large study looked at how age affects outcomes after transplant, using data from nearly 62,000 patients treated between 2013 and 2017.

Patients ranged in age from 18 to over 83, with most between 40 and 64 years old. Three years after transplant, overall survival (OS) rates were slightly lower with increasing age: 85.9% for those under 40, and 74.8% for those 75 and older. However, when researchers looked at excess mortality—how many patients died compared to what would be expected for their age group in the general population—the numbers were similar across all ages.

Although older patients had higher risks of complications and lower survival overall, age did not significantly increase the risk of relapse. These findings suggest that being older should not automatically rule out a stem cell transplant. With proper evaluation and care, many older adults with MM can still benefit from auto-HCT.

 

 

"MIDAS Study Group. Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma"

Source

Perrot A, Lambert J, Hulin C, Pieragostini A, Karlin L, Arnulf B, Rey P, Garderet L, Macro M, Escoffre-Barbe M, Gay J, Chalopin T, Gounot R, Schiano JM, Mohty M, Leleu X, Manier S, Mariette C, Chaleteix C, Braun T, De Prijck B, Avet-Loiseau H, Mary JY, Corre J, Moreau P, Touzeau C; MIDAS Study Group. Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma. N Engl J Med. 2025 Jul 31;393(5):425-437. doi: 10.1056/NEJMoa2505133. Epub 2025 Jun 3. 

Overview

This study looked at how measurable residual disease (MRD) testing could guide treatment for people with newly diagnosed multiple myeloma (MM) who are eligible for stem cell transplants. MRD helps show how much cancer remains after treatment, even when no signs of disease are visible. Patients first received powerful induction therapy using a four-drug combo called Isa-KRd. After that, they were split into groups based on their MRD results.

Patients who were MRD-negative—meaning no cancer was found at a sensitivity of one cancer cell per 100,000 normal cells—were randomly assigned to receive either a stem cell transplant followed by two more Isa-KRd cycles, or just six more Isa-KRd cycles without a transplant. At a more sensitive MRD level (1 in 1 million), the two groups showed nearly the same results: 86% in the transplant group and 84% in the drug-only group were still MRD-negative. This suggests skipping the transplant didn’t reduce effectiveness in these patients.

For patients who were still MRD-positive after initial treatment, researchers compared two strategies: a single transplant plus more Isa-KRd versus tandem transplants (two transplants). The MRD-negative rate at the higher sensitivity was 40% for the single transplant group and 32% for the tandem group—again, not a significant difference. Some patients in the tandem group didn’t even receive the second transplant.

Overall, the study found that tailoring treatment based on MRD results didn’t show major differences in deep response rates between groups. This could support the idea of avoiding more intensive treatments like tandem or even single transplants for some patients, without sacrificing outcomes. More follow-up is needed, but this trial points to the potential of MRD to personalize MM care.

 

 

"MIDAS Study Group. Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma"

Source

Marcoux, Curtis et al. Outcomes of Patients with Multiple Myeloma with deletion 1p Following Autologous Stem Cell Transplant. Transplantation and Cellular Therapy, Volume 0, Issue 0 July 31, 2025. 

Overview

This study looked at how measurable residual disease (MRD) testing could guide treatment for people with newly diagnosed multiple myeloma (MM) who are eligible for stem cell transplants. MRD helps show how much cancer remains after treatment, even when no signs of disease are visible. Patients first received powerful induction therapy using a four-drug combo called Isa-KRd. After that, they were split into groups based on their MRD results.

Patients who were MRD-negative—meaning no cancer was found at a sensitivity of one cancer cell per 100,000 normal cells—were randomly assigned to receive either a stem cell transplant followed by two more Isa-KRd cycles, or just six more Isa-KRd cycles without a transplant. At a more sensitive MRD level (1 in 1 million), the two groups showed nearly the same results: 86% in the transplant group and 84% in the drug-only group were still MRD-negative. This suggests skipping the transplant didn’t reduce effectiveness in these patients.

For patients who were still MRD-positive after initial treatment, researchers compared two strategies: a single transplant plus more Isa-KRd versus tandem transplants (two transplants). The MRD-negative rate at the higher sensitivity was 40% for the single transplant group and 32% for the tandem group—again, not a significant difference. Some patients in the tandem group didn’t even receive the second transplant.

Overall, the study found that tailoring treatment based on MRD results didn’t show major differences in deep response rates between groups. This could support the idea of avoiding more intensive treatments like tandem or even single transplants for some patients, without sacrificing outcomes. More follow-up is needed, but this trial points to the potential of MRD to personalize MM care.

 

 

"Outcomes of Patients with Multiple Myeloma with deletion 1p Following Autologous Stem Cell Transplant."

Source

Marcoux, Curtis et al. Outcomes of Patients with Multiple Myeloma with deletion 1p Following Autologous Stem Cell Transplant. Transplantation and Cellular Therapy, Volume 0, Issue 0 July 31, 2025. . 

Overview

This study looked at how a specific genetic change, called del(1p), affects outcomes in patients with newly diagnosed multiple myeloma (MM) who undergo autologous stem cell transplant (autoHCT). Previous research suggested that del(1p), a deletion on the short arm of chromosome 1, may be linked to worse survival, but it wasn’t clear how it impacts patients receiving today’s standard treatments.

Researchers analyzed data from 55 patients with del(1p) who received upfront autoHCT between 2010 and 2021. After about two years of follow-up, the median time before the cancer came back (progression-free survival, or PFS) was just over 30 months. Most patients were still alive, so the overall survival (OS) median had not yet been reached.

They found that women and patients with more advanced disease (R2-ISS stage IV) had worse PFS, while those who achieved a complete response after transplant had better outcomes. Importantly, patients who also had another high-risk genetic marker, del(17p), along with del(1p), had significantly worse survival.

When the researchers compared patients with del(1p) to similar patients without it, they found no significant differences in PFS or OS. This suggests that del(1p) alone may not lead to worse outcomes for patients who receive modern treatments and undergo transplant. However, the combination of del(1p) and del(17p) may still signal a higher-risk disease that needs closer attention.