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 September 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 September 2025)

"Prognostic value of minimal residual disease detected by EuroFlow next-generation flow cytometry and next-generation sequencing in patients with multiple myeloma achieving complete response and receiving lenalidomide maintenance after autotransplant: a prospective comparison study"

Source

Yoroidaka T, Takamatsu H, Urushihara R, Itagaki M, Yoshihara S, Sato K, Takezako N, Ozaki S, Suzuki K, Kohno K, Muta T, Matsumoto M, Terasaki Y, Yamashita T, Fuchida S- ichi, Sakamoto J, Ishida T, Suzuki K, Murakami H, Durie BG, Shimizu K. Prognostic value of minimal residual disease detected by EuroFlow next-generation flow cytometry and next-generation sequencing in patients with multiple myeloma achieving complete response and receiving lenalidomide maintenance after autotransplant: a prospective comparison study. Haematologica 2025;110(9):2160-2170; https://doi.org/10.3324/haematol.2025.287411.  September 1, 2025. 

Overview

This study looked at how well advanced testing methods can measure minimal residual disease (MRD) in people with multiple myeloma who received an autologous stem cell transplant followed by lenalidomide maintenance. Researchers studied patients from several centers in Japan who had reached complete response or stringent complete response within the first year after transplant. They checked MRD in bone marrow using two highly sensitive tools—next-generation flow cytometry (NGF) and next-generation sequencing (NGS)—at three different times: within a year after transplant, at one year, and at two years.

A total of 52 patients were included, and the results showed that NGF and NGS gave very similar MRD measurements. After three years of follow-up, the progression-free survival rate was about 76%, while overall survival was about 96%. Importantly, patients who stayed MRD-negative for more than six months had much better outcomes, with significantly higher chances of remaining free from disease progression compared to those who did not maintain MRD negativity. This benefit was seen with both NGF and NGS testing.

The study confirms that NGF and NGS are reliable ways to measure MRD, and that sustained MRD negativity is strongly linked with longer progression-free survival in multiple myeloma patients after transplant.

 

 

"Bicistronic CAR T Cell against BCMA and CD229 Effectively Controls Myeloma Even When BCMA Expression Is Limited"

Source

Luis Gerardo Rodríguez-Lobato, Oriol Cardús, Joan Mañé-Pujol, Anthony M. Battram, Sergi Vaqué-Salsench, Judith Carpio, Lorena Pérez-Amill, Hugo Calderón, Beatriz Martín-Antonio, Aina Oliver-Caldés, Ester Lozano, David F. Moreno, Valentin Ortiz-Maldonado, Maria Queralt Salas, Anna de Daniel, Natalia Tovar, M. Teresa Cibeira, Laura Rosiñol, Joan Bladé, Manel Juan, Álvaro Urbano-Ispizua, Pablo Engel, Carlos Fernández de Larrea; Bicistronic CAR T Cell against BCMA and CD229 Effectively Controls Myeloma Even When BCMA Expression Is Limited. Cancer Immunol Res 1 September 2025; 13 (9): 1374–1390. https://doi.org/10.1158/2326-6066.CIR-24-1313 

Overview

This study explored new strategies to improve CAR T-cell therapy for patients with relapsed or refractory multiple myeloma. While CAR T cells that target BCMA have shown strong initial responses, most patients eventually relapse because the cancer cells lose or reduce BCMA on their surface. To address this, researchers tested CAR T cells that target CD229, another protein found on myeloma cells, as well as a dual CAR T-cell design that targets both BCMA and CD229.

The CD229-targeting CAR T cells worked effectively in lab and animal models, even when BCMA levels varied. The dual CAR T cells also showed strong activity, not only against tumors with consistent BCMA expression but also against cases where some cancer cells had deleted or reduced BCMA. Importantly, the therapy did not cause harmful “self-killing” of CAR T cells, though there was some limited activity against normal resting T cells. In some situations, targeting CD229 put selective pressure on the cancer, causing it to lose CD229 expression.

Overall, the findings suggest that CD229 is a promising target for CAR T-cell therapy, either alone or in combination with BCMA, and could help overcome relapses linked to the loss of BCMA in multiple myeloma.

 

 

"Determining the factors affecting bortezomib’s adverse events in the treatment of newly diagnosed multiple myeloma"

Source

Dong, M., Han, X., He, J., Yang, L., Zheng, G., & Cai, Z. (2025). Determining the factors affecting bortezomib’s adverse events in the treatment of newly diagnosed multiple myeloma. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2548069  September 1, 2025. 

Overview

This study examined the side effects of bortezomib, a proteasome inhibitor widely used to treat multiple myeloma. Researchers compared different ways of giving the drug and looked at factors that might influence how patients respond. They focused on common side effects, including peripheral neuropathy, infection, digestive issues, and constipation.

The study included patients who received bortezomib either by intravenous (IV) or subcutaneous (SC) injection. Results showed that patients treated with SC injections had fewer side effects, particularly peripheral neuropathy, infection, and digestive problems, without reducing the drug’s effectiveness. When comparing doses, patients who received a reduced dose of bortezomib had higher rates of infection, though treatment outcomes were similar to those on standard doses. Disease stage also played a role: patients with stage III disease experienced more severe peripheral neuropathy compared to those with stage I.

Administering bortezomib by SC injection appears to lower the risk of certain side effects while maintaining its effectiveness; however, reduced dosing may increase the risk of infection. Patients with advanced disease are also more likely to develop severe neuropathy.

 

 

"Doubling in median survival in patients diagnosed with multiple myeloma 2005-2019; a real-world study from the UK’s Haematological Malignancy Research Network"

Source

Smith A, Bagguley T, Roman E, Crouch S, Patmore R, De Tute R, Rawstron A, Cook G, Seymour F, Parrish C. Doubling in median survival in patients diagnosed with multiple myeloma 2005-2019; a real-world study from the UK’s Haematological Malignancy Research Network. Haematologica 2025;110(9):2203-2208; https://doi.org/10.3324/haematol.2024.287095.  September 1, 2025.  

Overview

This study examined how the diagnosis, treatment, and survival of multiple myeloma patients in the UK have changed between 2005 and 2019, using real-world data from more than 3,700 people tracked through the Haematological Malignancy Research Network. Patients had a median age of about 73 years, with nearly one-third first presenting to hospital as an emergency. Over time, improvements in diagnostic methods, staging, and treatment options were observed. For example, cross-sectional imaging replaced traditional skeletal surveys, and the proportion of patients diagnosed without classic CRAB symptoms increased after new diagnostic criteria were introduced in 2014.

Treatment patterns shifted significantly during this period. Use of older regimens such as cyclophosphamide, thalidomide, and dexamethasone declined, while bortezomib-based combinations became more common after 2011, especially the triplet regimen of bortezomib, cyclophosphamide, and dexamethasone. This change coincided with major improvements in survival. Median survival nearly doubled, from 2.4 years in 2005-2007 to 4.5 years in 2017-2019. Five-year overall survival rose from about 31% to 46%, with especially notable gains among patients aged 80 and older—an age group that had previously shown little improvement.

These results show that advances in therapy are not only extending life for patients in clinical trials but also in routine practice across the NHS. The improvements in the oldest and frailest patients highlight how better drug delivery, dose adjustments, and universal healthcare access can help extend the benefits of modern treatments to groups often excluded from trials. Overall, the study confirms that real-world outcomes for myeloma patients in the UK have steadily improved, particularly since the adoption of bortezomib-based regimens.

 

 

"Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial"

Source

Manier S, Dimopoulos M-A, Leleu XP, Moreau P, Cavo M, Goldschmidt H, Orlowski RZ, Tron M, Tekle C, Brégeault M-F, Shafer AT, Beksac M, Facon T. Isatuximab plus bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma patients: a frailty subgroup analysis of the IMROZ trial. Haematologica 2025;110(9):2139-2150; https://doi.org/10.3324/haematol.2024.287200.  September 1, 2025. 

Overview

This analysis looked at frailty in patients with newly diagnosed, transplant-ineligible multiple myeloma who were enrolled in the IMROZ phase III trial. Frailty was assessed using the simplified International Myeloma Working Group frailty score, with about one-quarter of patients classified as frail. All patients received standard VRd treatment (bortezomib, lenalidomide, dexamethasone), with or without isatuximab (Isa), followed by Rd or Isa-Rd maintenance.

After nearly five years of follow-up, adding isatuximab to VRd improved progression-free survival in both frail and non-frail patients. Among frail patients, Isa-VRd reduced the risk of progression or death by almost half compared to VRd alone. Frail patients receiving Isa-VRd were also more likely to achieve minimal residual disease negativity and complete response. Importantly, the rates of treatment discontinuation due to side effects were similar between groups, regardless of frailty status.

These findings show that Isa-VRd is effective and well tolerated in frail patients who cannot undergo transplant, offering meaningful improvements in survival and depth of response without added safety concerns.

 

 

"Early identification of functional high-risk multiple myeloma patients after transplant: the predictive power of fat fraction and Response Assessment Category score in diffusion-weighted whole-body magnetic resonance imaging"

Source

Belotti A, Frittoli B, Terlizzi S, Ribolla R, Crippa C, Saeli C, Ferrari S, Bianchetti N, Bottelli C, Cattaneo C, Carbone C, Gullino A, Chiarini M, Giustini V, Roccaro A, Grazioli L, Tucci A. Early identification of functional high-risk multiple myeloma patients after transplant: the predictive power of fat fraction and Response Assessment Category score in diffusion-weighted whole-body magnetic resonance imaging. Haematologica 2025;110(9):2151-2159; https://doi.org/10.3324/haematol.2025.287409.  September 1, 2025.  

Overview

This study explored whether advanced MRI measures can help identify multiple myeloma patients at high risk of early relapse after autologous stem cell transplant. Researchers looked at diffusion-weighted whole-body MRI (DW-MRI) findings in 97 patients and used two tools: the Response Assessment Category (RAC), which grades response from complete remission to progression, and the relative fat fraction (rFF), which reflects bone marrow composition.

They found that an rFF threshold of 17.2% could predict early relapse with high accuracy. Patients with rFF above this cutoff had much longer progression-free survival and higher three-year overall survival rates compared to those with lower rFF values. Combining RAC and rFF provided even clearer stratification: patients with RAC 1 and high rFF had the best outcomes, while those with RAC ≥2 and low rFF had the worst, with relapse occurring in just over a year on average.

The results suggest that rFF adds important prognostic value to RAC scoring, and together they can help identify functional high-risk myeloma patients after transplant who are more likely to relapse early. This combined approach could guide closer monitoring and earlier intervention in this vulnerable group.

 

 

"Multiple myeloma associated long non-coding RNA PLUM confers chemoresistance by enhancing PRC2 mediated UPR pathway activation"

Source

Deka, K., Carter, JM., Bahai, A. et al. Multiple myeloma associated long non-coding RNA PLUM confers chemoresistance by enhancing PRC2 mediated UPR pathway activation. Nat Commun 16, 8155 (2025). https://doi.org/10.1038/s41467-025-63256-x September 1, 2025.   

Overview

This study investigated why some patients with relapsed or refractory multiple myeloma develop resistance to treatment. Researchers focused on the non-canonical NF-κB pathway, which is often mutated in high-risk cases. They identified a long non-coding RNA called PLUM that is overexpressed in these patients, especially those who do not respond to the common VRd regimen (bortezomib, lenalidomide, dexamethasone).

PLUM was found to interact with the Polycomb Repressive Complex 2 (PRC2), stabilizing it and boosting the activity of EZH2, a key histone-modifying enzyme. This altered the epigenetic landscape of myeloma cells by suppressing tumor suppressor genes such as FOXO3 and ZFP36, ultimately triggering the unfolded protein response and promoting drug resistance.

Importantly, when researchers blocked the interaction between PLUM and EZH2 using antisense oligonucleotides, myeloma cells became sensitive to treatment again in animal models. This was linked to loss of PRC2 stability and reduced EZH2 activity.

Overall, the findings suggest that PLUM plays a critical role in driving chemoresistance in high-risk myeloma, and targeting the PLUM-EZH2 interaction could be a promising new treatment strategy for relapsed, refractory disease.

 

 

"Palmitic acid adjunctive therapy upregulates bax/bcl-2 ratio and displays apoptosis as mode of anti-tumorigenic effects in multiple myeloma cells"

Source

Kapoor, S., Gupta, N., Raja, K. D., Qamar, I., Singh, A., & Sharma, A. (2025). Palmitic acid adjunctive therapy upregulates bax/bcl-2 ratio and displays apoptosis as mode of anti-tumorigenic effects in multiple myeloma cells. Leukemia & Lymphoma, 1–13. https://doi.org/10.1080/10428194.2025.2547246  September 1, 2025.  

Overview

This study explored the potential of palmitic acid as an anti-cancer agent in multiple myeloma. Researchers tested its effects in the lab, both alone and in combination with lenalidomide, a standard treatment for the disease.

Palmitic acid showed dose-dependent toxicity against myeloma cells and triggered apoptosis, or programmed cell death. When combined with lenalidomide, it enhanced these effects even at lower doses, leading to stronger cancer cell killing and cell cycle arrest in the G1 phase. The mechanism involved disruption of the mitochondrial membrane potential and an increased Bax/Bcl-2 ratio, both key signals for apoptosis.

The findings suggest that palmitic acid has significant tumor-suppressing activity and can boost the effectiveness of lenalidomide, pointing to its potential as a complementary therapy for multiple myeloma.

 

 

"Beyond ISS staging: the prognostic value of the Inflammation Prognostic Score Index (IPSI) in multiple myeloma"

Source

Huang, X., Wu, J., Li, S., Lu, Q., Huang, X., & Li, R. (2025). Beyond ISS staging: the prognostic value of the Inflammation Prognostic Score Index (IPSI) in multiple myeloma. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2549959  September 1, 2025. 

Overview

This study developed a new tool, the Inflammation Prognostic Score Index (IPSI), to better predict outcomes in patients with newly diagnosed multiple myeloma. Researchers analyzed 98 patients and focused on three blood-based markers: red cell distribution width (RDW), platelet count (PLT), and neutrophil-to-monocyte-to-lymphocyte ratio (NMLR). Each abnormal value was given one point, creating three IPSI groups based on total score: low risk (0–1), intermediate risk (2), and high risk (3).

The results showed clear differences in survival. Patients in the low-risk group lived a median of 24 months, compared to 21.5 months in the intermediate group and just 14 months in the high-risk group. IPSI was confirmed as an independent predictor of survival, with much higher risk of death in patients with two or three abnormal factors. Importantly, IPSI also worked alongside the International Staging System (ISS), adding extra precision in identifying high-risk patients within each ISS stage. Other inflammatory markers, such as SII and SIRI, were linked to ISS but were not independent predictors.

Overall, IPSI is a simple and cost-effective tool that improves current staging systems and could be especially valuable in settings where advanced molecular testing is not available

 

 

"Leveraging quantitative systems pharmacology modeling for elranatamab regimen optimization in relapsed or refractory multiple myeloma"

Source

Poels, K.E., Elmeliegy, M., Hibma, J. et al. Leveraging quantitative systems pharmacology modeling for elranatamab regimen optimization in relapsed or refractory multiple myeloma. npj Syst Biol Appl 11, 102 (2025). https://doi.org/10.1038/s41540-025-00585-z  September 1, 2025. 

Overview

Researchers studied Elrexfio™(elranatamab), a bispecific antibody approved for people with relapsed or refractory multiple myeloma. This drug works by linking T cells to myeloma cells through the BCMA marker, allowing the immune system to attack the cancer. A challenge in treatment is the presence of soluble BCMA (sBCMA) in the blood, which reflects disease burden and may reduce how well the drug works. To better understand this, scientists built a detailed model that mimics how elranatamab interacts with the body and the disease. Using clinical data, they tested different scenarios to account for differences between patients, drug behavior, and tumor biology. Their simulations showed that a weekly 76 mg dose is effective, even for patients with high sBCMA levels. The model also suggested that less frequent dosing could still maintain the drug’s benefit. This research highlights how advanced modeling can guide dosing decisions for bispecific antibodies in multiple myeloma.

 

 

"Trends in multiple myeloma and cardiovascular disease-related mortality among older adults in the United States, 1999 to 2023: a CDC wonder database analysis"

Source

Faheem, Muhammad Shaheer Bina; Hassan, Syed Tawassulb; Siddiqui, Shahreena Atharc; Zeeshan, Nafilac; Khan, Muhammad Idrees MDd,*. Trends in multiple myeloma and cardiovascular disease-related mortality among older adults in the United States, 1999 to 2023: a CDC wonder database analysis. Annals of Medicine & Surgery ():10.1097/MS9.0000000000003834, September 02, 2025. | DOI: 10.1097/MS9.0000000000003834  

Overview

Multiple myeloma is often linked with heart and blood vessel problems, and when both conditions occur together, the risk of serious complications and death rises—especially in older adults. To understand this better, researchers studied national death records from 1999 to 2023. They looked at people aged 65 and older who had both multiple myeloma and cardiovascular disease. Over this period, there were nearly 100,000 deaths connected to the two conditions. The overall death rate rose slightly, from 9.6 per 100,000 in 1999 to 9.9 in 2023, with the sharpest increase between 2018 and 2021. Men had almost twice the death rate of women, and non-Hispanic African Americans had the highest rates of all, about three times higher than other groups. Death rates were also higher in cities and in the Northeast region of the U.S. The study shows that more focused care and resources are needed to address these disparities and reduce deaths in vulnerable groups.

 

 

"Identification of a CD138-negative therapy-resistant subpopulation in multiple myeloma with vulnerability to splicing factor inhibition"

Source

Takahiro Kamiya, Masahiko Ajiro, Motohiko Oshima, Shuhei Koide, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Akiho Tsuchiya, Satoshi Kaito, Naoki Itokawa, Ryoji Ito, Kiyoshi Yamaguchi, Yoichi Furukawa, Bahityar Rahmutulla, Atsushi Kaneda, Takayuki Shimizu, Noriko Doki, Taku Kikuchi, Nobuhiro Tsukada, Masayuki Yamashita, Shinichiro Okamoto, Akihide Yoshimi, Keisuke Kataoka, Atsushi Iwama; Identification of a CD138-negative therapy-resistant subpopulation in multiple myeloma with vulnerability to splicing factor inhibition. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-24-0340  September 2, 2025. 

Overview

Scientists are working to understand why some multiple myeloma cells resist treatment. In this study, they used single-cell RNA sequencing on bone marrow samples from patients to look closely at individual myeloma cells. They found that the cancer is made up of different cell types, with some showing the ability to change their characteristics. A small group of cells that lacked the CD138 marker stood out as therapy-resistant. These cells had major changes in how their genes were regulated and showed abnormal activity in the splicing process, which helps cells edit RNA. One protein involved in this, RBM39, was found at high levels in the resistant cells. When researchers blocked RBM39—either by altering the gene or using drugs—the resistant cells were killed while other cells were spared. This suggests that targeting the splicing pathway, and RBM39 in particular, could be a new way to overcome drug resistance in multiple myeloma.

 

 

"Serum heat shock protein family A member 9 protein as a biomarker for bortezomib resistance and poor prognosis in patients with multiple myeloma"

Source

Takahiro Kamiya, Masahiko Ajiro, Motohiko Oshima, Shuhei Koide, Yaeko Nakajima-Takagi, Kazumasa Chen, Lina; Gao, Shuanga; Lin, Lia; Liu, Sua; Ma, Jinga; Zhang, Zhiyinga; Li, Qiana,b. Serum heat shock protein family A member 9 protein as a biomarker for bortezomib resistance and poor prognosis in patients with multiple myeloma. Anti-Cancer Drugs ():10.1097/CAD.0000000000001764, September 03, 2025. | DOI: 10.1097/CAD.0000000000001764 September 3, 2025.  

Overview

Velcade® (bortezomib) is an important drug for treating multiple myeloma, but resistance to it is a major problem that reduces its long-term effectiveness. To find ways of predicting resistance, researchers studied certain proteins that may play a role in how the drug works. They analyzed blood samples from 46 newly diagnosed patients—38 who responded to bortezomib and 8 who did not—as well as from 52 healthy people. The team measured levels of four proteins: HSPA9, DKK1, PSMD14, and TRIM21. They found that patients with multiple myeloma had higher levels of HSPA9 and DKK1 and lower levels of TRIM21 compared to healthy individuals. Most importantly, HSPA9 was the only protein that was significantly higher in patients who were resistant to bortezomib. High HSPA9 levels were also linked with more advanced disease, unfavorable lab results, resistance to treatment, and shorter survival. These findings suggest that HSPA9 could serve as a reliable biomarker for identifying patients at risk of bortezomib resistance and poor outcomes

 

 

"Treatment Accessibility, Availability, and Healthcare Costs for Multiple Myeloma in South Asian Countries"

Source

Uday Yanamandra, Celine Raphael, Roopika Peela, Abu Jafar Mohammad Saleh, Thinley Dorji, Hassan Juneh, Aye Aye Gyi, Ajay Jha, Mohammad Ayaz Mir, Buddhika Somawardana, Amin Lutful Kabir, Bishesh Poudyal, Manu Wimalachandra, Zeba Aziz, Senani Williams, Saad Usmani, Shaji Kumar, Pankaj Malhotra, Treatment Accessibility, Availability, and Healthcare Costs for Multiple Myeloma in South Asian Countries, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.09.002. September 3, 2025.  

Overview

Multiple myeloma cases are increasing worldwide, including in South Asia, but access to modern care remains uneven. To better understand these challenges, researchers surveyed doctors treating myeloma patients in eight South Asian countries. They examined availability of treatments, diagnostics, and transplant services, as well as patient costs. The study found that patients pay an average of 70% of their medical expenses out of pocket, placing a heavy financial burden on families. Basic tests such as protein electrophoresis and light chain assays were often unavailable in public hospitals, and advanced tools like PET scans and MRD testing were limited or too costly. While common drugs like lenalidomide and bortezomib were available in most countries, advanced therapies such as daratumumab were largely confined to private hospitals. Stem cell transplants were offered in many countries, but supportive infrastructure like cryopreservation was rare. Overall, the study highlights major gaps in access, showing that patients often depend on private care and face high costs. The authors stress the need for stronger policies, funding programs, and partnerships to improve treatment equity for myeloma patients across South Asia.

 

 

"Assessment and treatment of frail patients living with multiple myeloma. A guideline on behalf of the UK Myeloma Research Alliance Frailty Group"

Source

Moore S, Miller H, Parrish C, Seymour F, Miller L, Chandler T, et al. Assessment and treatment of frail patients living with multiple myeloma. A guideline on behalf of the UK Myeloma Research Alliance Frailty Group. Br J Haematol. 2025; 00: 1–13. https://doi.org/10.1111/bjh.70041 September 3, 2025.   

Overview

Frailty is when age and health problems make the body less able to handle stress, illness, or treatment. In multiple myeloma, which is most often diagnosed around age 69, frailty is very common. Up to half of newly diagnosed patients are frail, and this number climbs to nearly three-quarters at relapse. Frailty worsens treatment side effects, shortens survival, and lowers quality of life.

Doctors use different scoring tools to measure frailty in myeloma patients. The most widely used is the International Myeloma Working Group Frailty Score, which looks at age, daily function, and other health issues. Other tools, such as the Revised Myeloma Co-Morbidity Index, the UK Myeloma Risk Profile, and the Mayo Clinic frailty score, add lab results or disease features. While the International Myeloma Working Group score is considered the “gold standard,” it takes time to complete, so simpler versions are sometimes used in practice.

Frailty is not fixed—it can improve or worsen during treatment. In clinical trials, frail patients still benefit from newer, more effective drug combinations, but they also experience more side effects. Adjusting drug doses based on frailty helps reduce toxicity without sacrificing effectiveness. Steroids, which are common in myeloma treatment, often cause significant side effects in older adults; reducing or stopping them can be safe once remission is achieved. Newer therapies like bispecific antibodies and CAR T-cell therapy are effective, even in frailer patients, but infection risk and certain toxicities must be managed carefully.

Every newly diagnosed patient who is not eligible for a transplant should have a frailty assessment. Fit patients may benefit from four-drug combinations, while frail or older patients may do better with adjusted three-drug regimens. Supportive care such as bone-strengthening drugs, infection prevention, and immunoglobulin replacement is essential at all stages. In the future, care will increasingly focus on tailoring treatment to frailty status, with more holistic assessments that include physical, mental, and social health.

Frailty strongly affects how multiple myeloma patients respond to treatment. By carefully measuring frailty and adjusting therapy, doctors can improve survival, reduce side effects, and better protect patients’ quality of life.

 

 

"Microbiota Shape Metabolic and Immune Determinants of CAR-T Therapy and Correlate with Outcomes in Myeloma"

Source

Mireia Uribe-Herranz, Aina Oliver-Caldés, Neus Martínez-Micaelo, Marta Español-Rego, Maria Val-Casals, Roberto Martínez-Soler, Elisa Rubio-Garcia, Valeria Brunello, Erik Z. Mihelic, Nela Klein-González, Daniel Benítez-Ribas, Núria Amigó, Andrea Vergara, Valentin Ortiz-Maldonado, Luis Gerardo Rodríguez-Lobato, Julio Delgado, Iñaki Ortiz de Landazuri, Verónica González-Calle, Valentín Cabañas, Beatriz Martin-Antonio, Lorena Pérez-Amill, Juan Luis Reguera-Ortega, Paula Rodríguez-Otero, Bruno Paiva, Joaquín Martínez-López, Maria-Victoria Mateos, Mariona Pascal, Álvaro Urbano-Ispizua, Europa Azucena González-Navarro, Carlos Fernández de Larrea, Manel Juan; Microbiota Shape Metabolic and Immune Determinants of CAR-T Therapy and Correlate with Outcomes in Myeloma. Blood Cancer Discov 1 September 2025; 6 (5): 484–504. https://doi.org/10.1158/2643-3230.BCD-24-0203 .   

Overview

Multiple myeloma is still incurable, even with advances like CAR T-cell therapy. In this study, researchers looked at how gut bacteria and metabolites—substances produced during digestion—affect outcomes in patients receiving a BCMA-directed CAR T-cell therapy called ARI0002h. They found that one metabolite, succinate, was linked to the persistence and function of CAR T-cells. In lab tests, adding succinate helped CAR T-cells develop a stronger memory type and improved their energy use. In mice with myeloma, a diet that boosted succinate levels led to longer-lasting CAR T-cells and signs of better tumor control. The researchers also discovered that certain gut bacteria, along with specific metabolites, were connected to how well patients responded to treatment. By combining these factors into predictive models, they could identify patients more likely to achieve a complete response within the first six months after infusion. These results suggest that gut health and metabolites may play an important role in shaping responses to CAR T-cell therapy and could help guide patient care in the future.

 

 

 

"Single-cell RNA sequencing reveals immune regulatory mechanisms and molecular therapeutic strategies in the microenvironment of multiple myeloma"

Source

Su, Qianga,b; Long, Kehanb; Adu, MoZiLic; Jiang, Meijunb; Li, Qiaochud; Wan, Xufenga; Cao, Jiana; Yue, Yana; Li, Shuoyuana; Ying, Zhendonge; Liu, Qibinf; You, Chaoqung,*; Zhang, Zhuanga,*; Wang, Duana,*. Single-cell RNA sequencing reveals immune regulatory mechanisms and molecular therapeutic strategies in the microenvironment of multiple myeloma. International Journal of Surgery ():10.1097/JS9.0000000000003306, September 03, 2025. | DOI: 10.1097/JS9.0000000000003306    

Overview

Researchers used advanced genetic analysis techniques to better understand how multiple myeloma develops and spreads in the body. They wanted to find new ways to treat this cancer by studying how different cells in the bone marrow communicate with each other and affect the disease.

The scientists used a powerful method called single-cell RNA sequencing to examine individual cells from multiple myeloma patients. This technique allowed them to see exactly which genes were active in tumor cells, immune cells, and supporting tissue cells. They also used computer analysis to study how these different cell types interact with each other and send signals back and forth. Additionally, they performed genetic studies to determine which genes might cause the disease versus those that might protect against it.

The research revealed that several important cellular pathways become overactive in multiple myeloma. These pathways, including PI3K-AKT-mTOR, WNT-β-catenin, and TGF-β, control how cells grow, survive, and communicate. When these pathways don't work properly, they help cancer cells multiply and avoid being destroyed by the immune system. The study identified specific genes that contribute to the disease, such as HLA-C, CTSS, and LRRFIP1, while other genes like SHISA5 and ISG15 appear to help protect against multiple myeloma.

The scientists also discovered how immune cells and tumor cells send messages to each other through special protein connections called ligand-receptor interactions. Understanding these communications is important because they can either help the body fight the cancer or allow the cancer to hide from the immune system. Using computer modeling, the researchers identified potential new drugs, including natural compounds like actein, that might be able to block specific proteins involved in the disease.

These findings suggest that targeting the overactive cellular pathways and the communication systems between different cell types could lead to new treatments for multiple myeloma. The researchers believe that focusing on immune-related pathways and using small molecules to target specific proteins could provide fresh approaches to treating this challenging cancer. This work helps scientists better understand why current treatments eventually stop working and points toward new strategies that might be more effective in controlling the disease.

 

 

"Infection risk in 158 patients with relapsed/refractory multiple myeloma treated with bispecific antibodies: a single-center experience"

Source

Cani L, Scott SA, Roberts D, Joseph NS, Hofmeister CC, Gupta VA, Dhodapkar MV, Lonial S, Nooka AK, Kaufman JL. Infection risk in 158 patients with relapsed/refractory multiple myeloma treated with bispecific antibodies: a single-center experience. Haematologica; https://doi.org/10.3324/haematol.2025.288187 [Early view]. September 4, 2025.    

Overview

Researchers studied infection rates in 158 multiple myeloma patients who received bispecific antibody treatments, which are newer cancer drugs that help the immune system fight cancer cells. These medications can make patients more likely to get infections, so doctors need to take steps to prevent serious complications. The study looked at patients who received four different types of these antibodies over several months to understand how often infections occurred and what could be done to reduce the risks.

The patients were divided into two main groups based on which type of bispecific antibody they received. One group of 101 patients got antibodies that target a protein called BCMA, while 57 patients received an antibody targeting a different protein called GPRC5D. All patients received preventive treatments to protect them from certain infections, including medications to prevent herpes zoster and a lung infection called Pneumocystis pneumonia. They also received monthly infusions of immunoglobulin, which contains antibodies that help fight infections. Doctors monitored patients carefully for cytomegalovirus, a common virus that can cause serious problems in people with weakened immune systems.

The study found that infections were fairly common in both groups, but patients receiving the BCMA-targeting antibodies had slightly higher infection rates. About 39% of patients in the BCMA group developed infections within five months, compared to 28% in the GPRC5D group. Most of the infections were caused by viruses rather than bacteria, and many affected the upper respiratory system like the nose, throat, and sinuses. Cytomegalovirus infections were particularly concerning, occurring in 45% of BCMA patients but only 27% of GPRC5D patients within five months.

One of the most important findings was that patients who received monthly immunoglobulin infusions had a much lower risk of developing severe infections. This preventive treatment reduced the chance of serious infections by more than half, showing that this protective measure is very effective. The research suggests that doctors should continue using immunoglobulin as a standard preventive treatment for patients receiving bispecific antibodies.

The study's results help doctors better understand the infection risks associated with these newer cancer treatments and confirm that preventive measures are crucial for patient safety. While the follow-up period was relatively short, the findings provide valuable guidance for managing multiple myeloma patients who receive bispecific antibody therapy. The research emphasizes the importance of careful monitoring for viral infections, especially cytomegalovirus, and supports the continued use of immunoglobulin therapy to prevent serious complications during cancer treatment.

 

 

"Représentation du risque infectieux chez les patients atteints de myélome multiple : une étude prospective multicentrique visant à adapter le rôle des infirmier(e)s en pratique avancée, (Representation of infectious risk in patients with multiple myeloma: A multicentric prospective study aimed at adapting the role of advanced practice nurses)"

Source

Ludivine Besse, Stéphane Moreau, Michelle Delpy, Représentation du risque infectieux chez les patients atteints de myélome multiple : une étude prospective multicentrique visant à adapter le rôle des infirmier(e)s en pratique avancée, (Representation of infectious risk in patients with multiple myeloma: A multicentric prospective study aimed at adapting the role of advanced practice nurses) Bulletin du Cancer, 2025, ISSN 0007-4551, https://doi.org/10.1016/j.bulcan.2025.06.008. September 4, 2025.   

Overview

A study conducted at three French hospitals examined how well multiple myeloma patients understand their risk of getting infections during their first year of treatment. Even though new cancer treatments have helped patients live longer, about 2% of multiple myeloma patients still die from infections in their first year, despite having access to preventive medications. Researchers wanted to see if advanced practice nurses could help reduce these infection-related deaths by better educating and supporting patients.

The researchers surveyed 60 multiple myeloma patients who were in their first year of treatment at the three hospitals over a two-month period. They asked patients questions about what they knew regarding infection risks, preventive antibiotics, and vaccinations. The survey included both multiple-choice questions and open-ended questions that allowed patients to explain their understanding in their own words.

The results revealed significant gaps in patient knowledge about staying safe from infections. Most patients did not fully understand how likely they were to get infections or what symptoms they should watch for and report to their healthcare team. Many patients were unaware that they should contact their doctors immediately if they developed fever, unusual fatigue, or other signs of infection. The study also found that patients often did not know the names of the preventive medications they were taking or understand why these treatments were important for protecting their health.

When it came to vaccinations, the researchers found mixed results. While most patients had received appropriate vaccinations overall, many had not received the pneumococcal vaccine, which protects against a type of bacteria that commonly causes serious lung infections in people with weakened immune systems. This gap in vaccination coverage could put patients at unnecessary risk for preventable infections.

The study highlighted that there was no clear, organized system for helping patients navigate their care and stay safe from infections. Patients often felt confused about who to contact when they had concerns and were unsure about the steps they should take to protect themselves. This lack of coordination could delay important medical care when patients develop early signs of infection.

Based on these findings, the researchers concluded that advanced practice nurses could play a crucial role in improving patient outcomes. These specially trained nurses could provide better education to help patients understand their infection risks and recognize warning signs. They could also coordinate vaccination schedules, ensure patients understand their preventive medications, and serve as a reliable point of contact for both patients and the healthcare team. By filling these gaps in patient education and care coordination, advanced practice nurses might help reduce the number of multiple myeloma patients who die from preventable infections during their treatment.

 

 

"Minimal Residual Disease Negativity as the Primary Goal of Multiple Myeloma Therapy"

Source

Cooperrider, J.H., Derman, B.A. Minimal Residual Disease Negativity as the Primary Goal of Multiple Myeloma Therapy. Drugs (2025). https://doi.org/10.1007/s40265-025-02232-7  September 4, 2025   

Overview

Measurable residual disease testing, commonly called MRD testing, has become an important tool for doctors treating multiple myeloma because it can detect very small amounts of cancer cells that remain in the body after treatment. This testing provides much more detailed information about how well treatments are working compared to older methods that doctors used to measure treatment success. While MRD testing is most often done using bone marrow samples, doctors are also exploring ways to test for residual disease using blood samples and advanced imaging scans, which might give additional useful information when used together.

The most comprehensive approach to MRD testing involves checking for cancer cells in different parts of the body over time, which may give doctors the most accurate picture of how much disease remains. This detailed assessment has become so valuable that regulatory agencies now accept MRD results as evidence that new multiple myeloma treatments are working, allowing some medications to be approved more quickly. Many clinical trials now use MRD testing as their main way of measuring whether experimental treatments are successful.

Current clinical trials are using MRD test results to help decide how to customize treatment plans for individual patients. For example, doctors are studying whether patients who achieve very low levels of detectable disease might be able to reduce the intensity of their treatment or even stop certain maintenance medications while still staying in remission. Early research suggests that MRD testing could help guide these important treatment decisions, potentially allowing some patients to have treatment breaks while maintaining good disease control.

Despite these promising developments, there are still significant challenges that prevent MRD testing from being used routinely to guide all treatment decisions. The tests can be expensive and complex to perform, and doctors sometimes find it difficult to interpret the results and know exactly how to use the information in clinical practice. There are also questions about the best timing for these tests and when the results should influence treatment changes. Additionally, researchers still need more information about what to do when MRD levels start to rise again, which might signal that the cancer is beginning to return.

While achieving MRD negativity, meaning no detectable cancer cells, represents an exciting goal for both patients and researchers, more studies are needed to fully understand how to best use this testing in everyday patient care. Large, carefully designed clinical trials comparing different approaches will help doctors learn the most effective ways to incorporate MRD testing into treatment planning. These studies will provide clearer guidance on when to test, how to interpret results, and how to adjust treatments based on MRD findings, ultimately helping more multiple myeloma patients achieve the best possible outcomes.

 

 

"Timing genomic antigen loss in multiple myeloma treated with T-cell redirecting immunotherapies"

Source

Marios Papadimitriou, Sungwoo Ahn, Benjamin T. Diamond, Holly Lee, John B. McIntyre, Marietta Truger, Michael A. Durante, Bachisio Ziccheddu, Katalin Osz, Ola Landgren, Leo Rasche, Nizar J. Bahlis, Paola Neri, Francesco Maura; Timing genomic antigen loss in multiple myeloma treated with T-cell redirecting immunotherapies. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-25-0005  September 4, 2025. 

Overview

Researchers investigated why some multiple myeloma patients stop responding to newer immunotherapies called CAR-T cell therapy and T-cell engagers. These treatments work by targeting specific proteins on cancer cells, but sometimes the cancer cells lose these target proteins and become resistant to treatment. Scientists wanted to understand whether this resistance happens because cancer cells develop new genetic changes during treatment or because resistant cells were already present but too few to detect before treatment started.

The study used advanced genetic testing techniques to track when these resistance changes occurred in 11 patients with relapsed multiple myeloma. The researchers used a clever approach by looking at specific genetic patterns left behind by chemotherapy treatments, which act like timestamps showing when different genetic changes happened. This allowed them to determine whether the loss of target proteins occurred before or after patients started receiving the newer immunotherapies.

In four patients where they could determine the timing, the researchers found that the cancer cells lost their target proteins only after being exposed to the immunotherapy treatments. These genetic changes were not present when patients first started treatment, meaning the resistance developed as a direct response to the therapy rather than being selected from pre-existing resistant cells. The scientists confirmed this finding using a sensitive testing method called digital PCR, which showed that resistance mutations could not be detected when therapy began but appeared before patients experienced disease relapse.

To put these findings in perspective, the researchers also examined genetic data from 752 patients who were newly diagnosed with multiple myeloma. They found that very few of these patients had natural genetic changes that would make them resistant to these immunotherapies from the start. Only about 3% had partial loss of one target protein called TNFRSF17, and 9% had partial loss of another target called GPRC5D. Importantly, none of the newly diagnosed patients had complete loss of both copies of these genes, which would make the immunotherapies completely ineffective.

These results suggest that testing patients for genetic resistance markers before starting CAR-T cell therapy or T-cell engagers may not be very helpful, since resistance typically develops during treatment rather than existing beforehand. Instead, the findings highlight the importance of monitoring patients closely while they are receiving these therapies to detect early signs of resistance. This approach could help doctors identify when resistance is developing and potentially switch to different treatments before the cancer becomes fully resistant. The research provides valuable insights into how multiple myeloma adapts to these powerful new treatments and suggests strategies for better managing patients who receive these innovative therapies.

 

 

"Exploring research advances and future trends in drug resistance in multiple myeloma: A comprehensive bibliometric analysis"

Source

Yang, Xuanyu MBBSa; Lin, Fangzhen MBBSb; Zheng, Siteng MBBSb; Gao, Ye MBBSb; Li, Zhengyang MBBSc; Mei, Yuchen MBBSa; Xie, Yifan MBBSa; Ke, Jiayu MBBSd; Ling, Ling MDe,*. Exploring research advances and future trends in drug resistance in multiple myeloma: A comprehensive bibliometric analysis. Medicine 104(36):p e44279, September 05, 2025. | DOI: 10.1097/MD.0000000000044279. 

Overview

Researchers conducted a comprehensive review of scientific literature to understand global research trends in multiple myeloma drug resistance over the past decade. They analyzed over 3,300 published studies from 2015 to 2024 to identify which countries, institutions, and researchers are leading the field, what topics are being studied most intensively, and where future research efforts might be heading. This type of analysis helps scientists understand the big picture of research progress and identify areas that need more attention.

The study found that research publications on multiple myeloma drug resistance have been steadily increasing each year, with a particularly sharp rise from 2022 to 2024. This surge likely reflects growing recognition of drug resistance as a major challenge in treating multiple myeloma and increased funding for research in this area. The United States led global research efforts, producing about 36% of all publications, followed by China with nearly 29% of studies. Harvard Medical School emerged as the most influential research institution, likely due to its extensive cancer research programs and collaborations with other major medical centers.

When the researchers analyzed the specific topics being studied, they identified five main areas of focus in drug resistance research. These include developing new medications and treatment approaches, understanding the biological mechanisms that cause resistance, studying how individual cancer cells become resistant to drugs, examining how the surrounding tissue environment affects treatment response, and improving methods for diagnosing and monitoring resistance. This broad range of research topics shows that scientists are approaching the drug resistance problem from multiple angles to find comprehensive solutions.

Current research trends show that scientists are particularly interested in understanding how the tumor microenvironment contributes to drug resistance. The tumor microenvironment includes all the non-cancer cells, blood vessels, and supporting structures around the tumor that can influence how well treatments work. Researchers are also focusing heavily on developing new immunotherapies, which harness the body's immune system to fight cancer cells that have become resistant to conventional treatments.

The analysis revealed important patterns in how research institutions and countries collaborate on drug resistance studies. These collaborative networks help share knowledge, resources, and expertise across different research groups, potentially accelerating the discovery of new treatments. The study's findings provide valuable guidance for researchers, funding agencies, and policymakers who want to understand where to focus future efforts and resources.

The researchers concluded that this comprehensive view of the research landscape offers important insights for advancing the field. By identifying key contributors, emerging research priorities, and gaps in current knowledge, the analysis can help guide future investigations toward the most promising areas. This strategic approach to research planning could ultimately lead to faster development of more effective treatments for patients whose multiple myeloma has become resistant to current therapies, potentially improving outcomes for this challenging patient population.

 

 

"Impact of Dara-VTD induction therapy on stem cell mobilization outcomes in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation: a multicenter study"

Source

Della Pepa, R., Palmieri, S., Rocco, S. et al. Impact of Dara-VTD induction therapy on stem cell mobilization outcomes in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation: a multicenter study. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06581-x  September 5, 2025. 

Overview

Researchers studied how well a combination treatment called Dara-VTD works for collecting stem cells needed for bone marrow transplants in newly diagnosed multiple myeloma patients. This treatment combines daratumumab with three other medications: Velcade® (bortezomib), Thalomid® (thalidomide), and dexamethasone. While this four-drug combination is very effective at treating multiple myeloma, doctors wanted to make sure it doesn't interfere with the important process of collecting enough healthy stem cells for later transplantation.

The study looked at 81 patients who received Dara-VTD treatment between November 2021 and June 2023, comparing their stem cell collection results with 93 patients who had previously received the three-drug VTD combination without daratumumab. All patients were planning to have autologous stem cell transplants, which means they would receive their own stem cells back after high-dose chemotherapy. To collect these stem cells, doctors use special medications to move the cells from the bone marrow into the bloodstream, where they can be harvested through a process similar to blood donation.

The results showed that patients receiving Dara-VTD were still able to collect sufficient stem cells for transplantation. The median number of stem cells collected was 5.1 million cells per kilogram of body weight, and nearly all patients (96.3%) achieved the minimum target of 2 million cells per kilogram needed for a successful transplant. However, doctors did need to use a rescue medication called plerixafor much more often in the Dara-VTD group compared to the VTD group. About 56% of Dara-VTD patients needed plerixafor, while only 4% of VTD patients required this additional help.

The study found that using cyclophosphamide-based mobilization regimens worked better than other approaches for collecting stem cells in patients who had received Dara-VTD. This suggests that doctors can optimize stem cell collection by choosing the right mobilization strategy, even when patients have received the more intensive four-drug treatment. The researchers emphasized that individualized approaches to stem cell mobilization are important for achieving the best results.

Interestingly, patients in the Dara-VTD group actually recovered faster after their transplants than those in the VTD group. Their white blood cell counts returned to normal levels in 11 days compared to 12 days, and their platelet counts recovered in 13 days versus 17 days. This faster recovery suggests that despite any challenges in collecting stem cells, the quality of the collected cells remained excellent and supported robust blood cell recovery after transplantation.

The researchers concluded that while daratumumab does present some challenges for stem cell mobilization, requiring more frequent use of rescue medications, it doesn't prevent successful stem cell collection or compromise the transplant process. With proper planning and the right mobilization strategies, patients can still proceed with autologous stem cell transplants after receiving this highly effective four-drug induction therapy. This finding is important because it means doctors can continue using this powerful treatment combination without worrying that it will prevent patients from receiving potentially life-saving transplants.

 

 

"Long-term outcome following vertebroplasty or bone cementoplasty in multiple myeloma patients"

Source

Soliman, S., Garderet, L., Premat, K. et al. Long-term outcome following vertebroplasty or bone cementoplasty in multiple myeloma patients. Neuroradiology (2025). https://doi.org/10.1007/s00234-025-03738-3  September 5, 2025. 

Overview

Researchers conducted a long-term study to evaluate how well bone cementoplasty works for multiple myeloma patients over time. Cementoplasty is a procedure where doctors inject medical cement into weakened or fractured bones to strengthen them and reduce pain. The study followed patients for more than five years after their procedures to see how durable this treatment is and what complications might develop over time.

The research team reviewed records from 154 multiple myeloma patients who had cementoplasty procedures between 2012 and 2017, focusing on 47 patients who had follow-up imaging scans available beyond five years. These patients had a total of 74 procedures that strengthened 142 bone sites, including 129 vertebrae in the spine, 11 areas in the pelvic region, and 2 other locations. Most of the treated sites were bones that had already fractured due to weakening from the cancer, while others were areas with holes caused by the disease but had not yet broken.

The results showed that cementoplasty is generally a safe and effective long-term treatment for multiple myeloma patients. No serious complications occurred during the procedures, and only 2 patients experienced new fractures in the same bones that had been treated with cement. This suggests that once bones are strengthened with cement, they rarely break again in the same location. The procedure appears to provide lasting structural support to weakened bones affected by multiple myeloma.

However, the study did identify some important concerns about adjacent vertebrae, which are the spine bones located next to those that received cement treatment. About 14% of patients developed fractures in vertebrae that were adjacent to cemented ones during the follow-up period. The researchers found that when cement leaked into the disc space between vertebrae during the original procedure, patients were much more likely to develop fractures in adjacent vertebrae later. This happened in 31% of cases with cement leakage compared to only 9% without leakage.

The study also found that 30% of patients developed new vertebral fractures in areas of the spine that were far away from the cemented sites. These remote fractures were more common in patients whose bone marrow had higher concentrations of myeloma cells, those whose multiple myeloma had relapsed or returned, and those who had fractures caused by general bone weakening rather than specific tumor-related damage. This suggests that the overall progression of the disease and the extent of bone involvement influence the risk of developing new fractures elsewhere in the skeleton.

Based on these findings, the researchers concluded that cementoplasty provides durable strengthening of treated bones in multiple myeloma patients, with very low rates of re-fracture at the same sites. However, the relatively high rate of fractures in adjacent vertebrae raises questions about whether doctors should consider preventively treating vertebrae next to the primary fracture site during the initial procedure. This prophylactic approach might help reduce the risk of future fractures in vulnerable adjacent bones, though more research would be needed to determine the best strategy for preventing these complications while maintaining the overall safety and effectiveness of the treatment.

 

 

"Angiogenesis in Multiple Myeloma: 25 Years of Research in This Field"

Source

D. Ribatti, “Angiogenesis in Multiple Myeloma: 25 Years of Research in This Field,” European Journal of Haematology (2025): 1–17, https://doi.org/10.1111/ejh.70023.  September 7, 2025. 

Overview

Since 1994, researchers have known that multiple myeloma is closely connected to angiogenesis, which is the process by which new blood vessels form to supply tumors with nutrients and oxygen. That year, scientists Vacca and Ribatti made a groundbreaking discovery when they found that patients with multiple myeloma had significantly more blood vessels in their bone marrow compared to people with a precancerous condition called monoclonal gammopathy of undetermined significance, or MGUS. They also observed that patients with active multiple myeloma had even more blood vessel growth than those with inactive disease, suggesting that angiogenesis plays an important role in how aggressive the cancer becomes.

This initial discovery opened up an entirely new area of research and treatment possibilities for multiple myeloma. Over the past three decades, scientists have been working to understand exactly how angiogenesis contributes to the development and progression of multiple myeloma. They have learned that as the cancer grows and spreads throughout the bone marrow, it needs an increasing blood supply to continue thriving. The tumor cells release special signals that encourage the formation of new blood vessels, creating a network that supports the cancer's growth and helps it resist treatment.

Based on this understanding, researchers began developing and testing medications that could block angiogenesis, hoping to starve tumors of their blood supply and slow or stop cancer progression. These anti-angiogenic drugs work by interfering with the signals that promote blood vessel formation or by directly attacking the new blood vessels that feed the tumor. The theory was that by cutting off the tumor's blood supply, these medications could make other cancer treatments more effective and improve patient outcomes.

However, the results from clinical studies using anti-angiogenic drugs in multiple myeloma have been mixed and sometimes disappointing. While some patients have benefited from these treatments, the overall effectiveness has not been as clear or consistent as researchers initially hoped. There has been ongoing debate in the medical community about which patients might benefit most from anti-angiogenic therapy and how these drugs should best be combined with other multiple myeloma treatments.

Despite these challenges and controversies, researchers continue to believe that targeting angiogenesis remains a promising approach for treating multiple myeloma. The fundamental role that blood vessel formation plays in tumor growth and progression suggests that finding the right way to block this process could still lead to significant treatment advances. Scientists are continuing to develop new and more effective anti-angiogenic medications, hoping to overcome the limitations of earlier drugs.

The ongoing research in this area reflects the complexity of multiple myeloma and the challenge of translating laboratory discoveries into effective treatments for patients. While anti-angiogenic therapy has not yet become a standard treatment approach, the continued scientific interest in this field demonstrates that researchers believe there is still untapped potential in targeting the blood vessels that support tumor growth. As our understanding of angiogenesis in multiple myeloma continues to evolve, new opportunities for more effective anti-angiogenic treatments may emerge, potentially offering better outcomes for patients in the future.

 

 

"Impact of Gamma-Secretase Inhibition on Outcomes Following BCMA CAR-T Therapy in Multiple Myeloma: A Comparison of Two Phase 1 Trials. Transplantation and Cellular Therapy"

Source

Portuguese, Andrew J et al. Impact of Gamma-Secretase Inhibition on Outcomes Following BCMA CAR-T Therapy in Multiple Myeloma: A Comparison of Two Phase 1 Trials. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 0, Issue 0 September 8, 2025.  

Overview

Researchers studied whether adding a medication called a gamma-secretase inhibitor could improve outcomes for multiple myeloma patients receiving CAR-T cell therapy. CAR-T therapy has revolutionized treatment for patients with relapsed multiple myeloma by genetically modifying their own immune cells to better attack cancer cells that display a protein called BCMA. While this treatment works well for many patients, some don't respond or relapse quickly, prompting scientists to look for ways to make it more effective.

The gamma-secretase inhibitor works by increasing the amount of BCMA protein displayed on the surface of cancer cells, potentially making them easier targets for the modified immune cells. This approach may be especially helpful for patients whose cancer cells naturally have low levels of BCMA, which could make the CAR-T therapy less effective. The researchers compared results from two similar clinical trials of the same CAR-T product called FCARH143, with one trial including the gamma-secretase inhibitor and the other using CAR-T therapy alone.

The study included 43 patients total, with 18 receiving the combination treatment and 25 receiving CAR-T therapy without the additional medication. Patients were followed for an average of nearly six years to assess long-term outcomes. The researchers divided patients into two groups based on whether they had previously received other BCMA-targeted treatments like other CAR-T therapies or bispecific antibodies. This distinction was important because prior exposure to BCMA-targeted treatments might affect how well the new therapy works.

The results showed that adding the gamma-secretase inhibitor provided significant benefits, but only for certain patients. Among patients who had never received BCMA-targeted treatments before, those who got the combination therapy lived much longer than those who received CAR-T alone. The median survival time was not yet reached in the combination group, compared to 2.3 years for CAR-T alone. There was also a trend toward longer progression-free survival, meaning patients stayed in remission longer before their cancer returned.

Importantly, the benefits were not seen in patients who had previously been treated with other BCMA-targeted therapies. This suggests that once patients have been exposed to treatments targeting BCMA, adding the gamma-secretase inhibitor may not provide additional advantages. The researchers also found that the combination approach seemed particularly helpful for patients whose cancer cells had low baseline levels of BCMA protein, supporting the theory that increasing BCMA expression makes the cancer cells more vulnerable to attack.

The safety profiles of both approaches were similar, with comparable rates of side effects including cytokine release syndrome and neurological complications that can occur with CAR-T therapy. This suggests that adding the gamma-secretase inhibitor doesn't increase the risk of serious side effects while potentially improving effectiveness in the right patient population.

These findings are particularly significant because they suggest a relatively simple strategy for improving CAR-T therapy outcomes in multiple myeloma. By identifying patients who might benefit most from this combination approach, specifically those who haven't received prior BCMA-targeted treatments and have low BCMA levels on their cancer cells, doctors could potentially personalize treatment to achieve better results. The researchers emphasize that these results, while promising, come from a retrospective comparison of two separate trials and should be confirmed in larger, prospective studies designed specifically to test this combination approach.

 

 

"Serum proteome profiling identified thrombospondin-1 and lactoferrin as biomarkers of relapsed multiple myeloma"

Source

Wu X, Guo J, Deng H, Chen W. Serum proteome profiling identified thrombospondin-1 and lactoferrin as biomarkers of relapsed multiple myeloma. Front Med (Lausanne). 2025 Sep 8;12:1640245. doi: 10.3389/fmed.2025.1640245. 

Overview

This study looked at how protein levels in the blood and bone marrow might serve as biomarkers for relapsed or refractory multiple myeloma (RRMM). Researchers compared samples from patients with newly diagnosed myeloma, those in remission, and those with RRMM, as well as from healthy individuals. Using advanced mass spectrometry, they measured more than 1,000 different proteins and then confirmed their findings with additional testing.

They discovered that two proteins, thrombospondin-1 (THBS1) and lactoferrin (LTF), were present at much lower levels in people with RRMM compared to all other groups. These results suggest that reduced levels of THBS1 and LTF could be linked to relapse and may serve as important markers to help identify and track disease progression in multiple myeloma.

 

 

"Multi-omics reveals immune features in immune and non-immune cells, an IFN-γ/IFN-α-B2M positive feedback loop, and targeted metabolic therapy in multiple myeloma"

Source

Li C, Liao Y, Xu L, Chen Y. Multi-omics reveals immune features in immune and non-immune cells, an IFN-γ/IFN-α-B2M positive feedback loop, and targeted metabolic therapy in multiple myeloma. Front Immunol. 2025 Sep 8;16:1575079. doi: 10.3389/fimmu.2025.1575079.  

Overview

This study explored how advanced single-cell technologies can reveal new insights into the biology of multiple myeloma. Researchers combined single-cell RNA sequencing, single-cell metabolism profiling, and bulk RNA sequencing to create a detailed “multi-omics atlas” of the disease. By analyzing both immune and non-immune cells, they were able to map out the subpopulations of cells and signaling pathways that help myeloma evade the immune system and continue to grow.

The analysis uncovered new subpopulations of cells, including myeloma-activated stem cells and a group of B cells marked by ISG15, both of which were linked to patient survival. The study also identified how certain immune cells secrete interferons that drive a feedback loop tied to disease progression. Importantly, using this multi-omics approach, the team screened potential drug candidates and found four that showed strong anti-myeloma effects in lab tests. These findings could guide new strategies for treatment and provide a deeper understanding of how the disease develops and resists therapy.

 

 

"RUNX1 expression dynamics in plasma cell differentiation and pathogenesis of multiple myeloma"

Source

Tang TF, Chan YT, Lim HJ, Cheok YY, Anuar NA, Cheong CS, Looi CY, Tan SM, Wong WF, Gan GG. RUNX1 expression dynamics in plasma cell differentiation and pathogenesis of multiple myeloma. Front Immunol. 2025 Sep 8;16:1643615. doi: 10.3389/fimmu.2025.1643615.    

Overview

This study looked at the role of a transcription factor called RUNX1 in the development of plasma cells and its possible connection to multiple myeloma. Researchers analyzed bone marrow and blood samples from patients with myeloma and compared them with samples from healthy donors. Using flow cytometry, they examined how different B cell and plasma cell populations developed and measured RUNX1 levels at each stage. They also tested the effects of reducing RUNX1 activity in B cells using laboratory methods.

The results showed that patients with myeloma had more plasma cells in their bone marrow compared to healthy individuals. RUNX1 expression was low in early B cells but steadily increased as the cells matured into plasma cells. Interestingly, plasmablasts from myeloma patients had higher RUNX1 levels than those from healthy donors, even though RUNX1 expression did not vary much across different stages of myeloma. When RUNX1 was knocked down in lab experiments, B cell differentiation was temporarily slowed. These findings suggest that RUNX1 plays a role in driving the final stages of B cell development and may influence how multiple myeloma progresses.
 

 

"Clinical applications of mass spectrometry in multiple myeloma"

Source

Benjamin A. Derman, Andrew J. Yee; Clinical applications of mass spectrometry in multiple myeloma. Blood Adv 2025; bloodadvances.2024015685. doi: https://doi.org/10.1182/bloodadvances.2024015685  September 8, 2025. 

Overview

This review highlights how mass spectrometry (MS) is becoming an important tool for monitoring multiple myeloma. Unlike standard blood tests such as serum protein electrophoresis or immunofixation, MS can detect and measure monoclonal proteins in the blood with far greater sensitivity—sometimes even matching or exceeding bone marrow–based methods like next-generation flow cytometry or sequencing.

Both major MS approaches, which analyze either intact light chains or clonotypic peptides, have shown strong potential for tracking disease. However, because monoclonal proteins take time to clear from the body, MS may not be the best method for assessing early treatment response. Despite this limitation, MS is now moving from research labs into commercial use, offering doctors and patients a powerful, non-invasive way to monitor myeloma without the need for frequent bone marrow biopsies.
 

 

"Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy"

Source

Tiziana Bruno, Maria Chiara Cappelletto, Clelia Cortile, Stefano Di Giovenale, Bruno Amadio, Francesca De Nicola, Italia Falcone, Stefano Giuliani, Belinda Palermo, Valeria Catena, Ludovica Ciuffreda, Fulvia Cerruti, Paolo Cascio, Roberta Merola, Serena Masi, Valentina De Pascale, Ombretta Annibali, Silvia Ferraro, Svitlana Gumenyuk, Francesco Pisani, Francesco Marchesi, Andrea Mengarelli, Maurizio Fanciulli, Giacomo Corleone; Nuclear respiratory factor 1 promotes cell survival in multiple myeloma under proteasome inhibition therapy. Blood 2025; blood.2025028441. doi: https://doi.org/10.1182/blood.2025028441  September 8, 2025. 

Overview

This study explored how changes in gene regulation help multiple myeloma cells survive and resist treatment. Researchers used ATAC-seq and computational analysis on bone marrow cells from patients to study chromatin accessibility, which influences how genes are turned on or off. They identified a key regulator called Nuclear Respiratory Factor 1 (NRF1) that plays a central role in keeping myeloma cells alive by controlling the ubiquitination pathway and maintaining proteasome balance—both essential processes for tumor survival.

The team also discovered a previously unknown enhancer element that boosts NRF1 activity. By targeting this enhancer with antisense oligonucleotides (ASOs), they were able to lower NRF1 levels and make myeloma cells more sensitive to bortezomib, a standard treatment. In animal models, ASOs used alone or in combination with bortezomib reduced tumor growth and extended survival. These findings reveal a new mechanism of myeloma survival and suggest that disrupting NRF1’s regulatory network could be a promising therapeutic strategy.
 

 

"From Physician-Driven to Patient-Centered: Transforming Multiple Myeloma Care Decisions"

Source

Richa Thakur et al. From Physician-Driven to Patient-Centered: Transforming Multiple Myeloma Care Decisions. JCO Oncol Pract 0, OP-25-00712 DOI:10.1200/OP-25-00712 September 8, 2025. 

Overview

Over the past decade, survival for patients with multiple myeloma has improved dramatically, with some living more than a decade and a small group achieving what appears to be cure. Long-term results from clinical trials, such as Total Therapy IV, now show overall survival well beyond 10 years for many patients. This represents a major shift in how the disease is understood, moving from a historically incurable cancer to one where lasting remission—and even cure—is possible for some.

At the same time, the regulatory and clinical trial landscape has changed. New treatments are often approved based on improvements in measurable residual disease (MRD) or progression-free survival (PFS), without waiting for overall survival (OS) data, which can take years to mature. While this accelerates patient access to promising therapies, it also means that patients and doctors are making decisions without knowing the full long-term survival impact. Trials like SWOG S0777 and MAIA have shown that OS benefits often appear only after extended follow-up, highlighting the challenges of balancing early access with certainty about long-term outcomes.

This approach has created tension between clinical trial goals and patient priorities. Many modern regimens require ongoing therapy, which can bring financial strain, treatment fatigue, and emotional stress. Surveys show that while patients value longer remission, quality of life often matters more than incremental PFS gains, especially when OS is unchanged. In one study, nearly half of patients said quality of life was their top concern, and more than one in five stated that treatments must improve OS—not just PFS—to be worth the side effects. Preferences also shift over time: patients who have lived longer with myeloma tend to favor less intensive approaches, reflecting the toll of ongoing treatment.

These findings underscore the need to integrate patient-reported outcomes into trial design and treatment planning. Tools already exist to measure the financial, emotional, and time-related burdens of therapy, but they are rarely used or reported in trials. Incorporating these measures more consistently could help align clinical progress with what matters most to patients: not just how long they live, but how well they live. As myeloma outcomes continue to improve, defining treatment success will require a stronger focus on patient experience and quality of life alongside traditional survival metrics.

 

 

"Soluble B-cell maturation antigen as a serum marker of MRD in patients with multiple myeloma"

Source

Dean EA, Li DM, Lin T, Sampson EM, Seifert RP, Hsu JW, Hiemenz JW, Wingard JR. Soluble B-cell maturation antigen as a serum marker of MRD in patients with multiple myeloma. Front Oncol. 2025 Sep 9;15:1631511. doi: 10.3389/fonc.2025.1631511.  

Overview

This study examined whether serum soluble B-cell maturation antigen (sBCMA) could serve as a reliable marker of residual disease in multiple myeloma. While sBCMA is already known to reflect high disease burden, its role in detecting minimal or measurable residual disease (MRD) has not been well studied. Researchers collected paired blood and bone marrow samples from 44 patients who were being evaluated for either their first or a salvage stem cell transplant.

The results showed that higher levels of sBCMA in the blood were strongly linked to the presence of overt disease in the bone marrow, as well as to MRD status. Patients with elevated sBCMA were more likely to have active disease, while those with lower levels were more likely to show MRD or no detectable disease. These findings suggest that measuring sBCMA in the blood could provide a non-invasive way to track tumor burden and potentially complement bone marrow–based MRD testing in multiple myeloma.

 

 

"A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death–Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma"

Source

Taxiarchis Kourelis, Sikander Ailawadhi, Dan T. Vogl, Sarah E. Gibson, Meaghen E. Sharik, Megan T. Du, Tyler D. Ames, Christina Y. Yim, Johan Baeck, Matthew R. Price, Jose M. Jimeno, Marta Chesi, P. Leif Bergsagel; A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death–Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-2574  September 9, 2025. 

Overview

This study evaluated PT-112, a new drug designed to trigger immunogenic cell death in cancer cells, for its potential use in multiple myeloma. PT-112 works by disrupting ribosome production and stressing cell organelles, leading to selective killing of tumor cells. Because of its pyrophosphate structure, the drug tends to accumulate in the bones, making it a promising option for bone-related cancers like myeloma.

In animal studies, PT-112 built up in bone as well as other organs and showed strong activity against myeloma in mouse models, both alone and in combination with other therapies. A phase I clinical trial tested the drug in patients with relapsed or refractory myeloma who had already gone through many prior treatments. PT-112 was safe, well-tolerated, and showed early signs of effectiveness, with a recommended dose set for further studies.

These findings suggest that PT-112 may work differently from standard therapies and could offer a new treatment option for patients with hard-to-treat myeloma, supporting the need for continued clinical trials.

 

 

"Patterns of progression among 427 patients with smoldering myeloma diagnosed after 2014: importance of monitoring"

Source

Efstathios Kastritis, Irene Solia, Panagiotis Malandrakis, Foteini Theodorakakou, Ioannis Ntanasis-Stathopoulos, Nikolaos Kanellias, Despina Fotiou, Magdalini Migkou, Evangelos Eleutherakis-Papaiakovou, Vassiliki Spiliopoulou, Nikoleta Kokkali, Asimina Papanikolaou, Stavroula Giannouli, Maria Gavriatopoulou, Evangelos Terpos, Meletios A. Dimopoulos; Patterns of progression among 427 patients with smoldering myeloma diagnosed after 2014: importance of monitoring. Blood Adv 2025; 9 (17): 4444–4447. doi: https://doi.org/10.1182/bloodadvances.2025016083  September 9, 2025.  

Overview

This letter shares new insights into how smoldering multiple myeloma (SMM) behaves in the era of modern diagnostic tools. Researchers analyzed data from 427 patients diagnosed with SMM between 2014 and 2023, using the updated International Myeloma Working Group (IMWG) criteria and advanced imaging methods such as low-dose CT, whole-body MRI, or PET/CT. Patients were closely monitored at regular intervals, with follow-up tailored to their risk level. For comparison, 486 patients with MGUS were also evaluated.

After a median of three years, only 10% of SMM patients progressed to symptomatic myeloma. Progression rates varied widely by risk group, with high-risk patients showing the greatest likelihood of developing active disease, while low-risk patients had very low rates of progression—similar to MGUS. Importantly, most cases of progression were identified through the SLiM criteria or by advanced imaging that detected early, asymptomatic bone lesions, rather than severe complications such as kidney failure.

These findings highlight that with modern imaging and criteria, the risks of sudden or severe complications from SMM are relatively low, especially for low-risk patients. The study underscores the need for ongoing careful monitoring and suggests that older clinical trial data may overestimate the risks of progression, since advanced imaging was not consistently used in the past. For most low-risk patients, observation remains appropriate, while intermediate- and high-risk groups may benefit from inclusion in clinical trials testing early interventions.

 

 

"European Myeloma Network Consensus Statement on Functional High-Risk Multiple Myeloma"

Source

S.-l. Lim, M. Engelhardt, E. Terpos, et al., “European Myeloma Network Consensus Statement on Functional High-Risk Multiple Myeloma,” American Journal of Hematology (2025): 1–13, https://doi.org/10.1002/ajh.70070.  September 9, 2025.  

Overview

This consensus statement focuses on a subset of multiple myeloma patients known as functional high-risk (FHR), who experience early disease progression despite initially appearing to have standard-risk disease. Multiple myeloma is a blood cancer marked by excess plasma cells in the bone marrow and complications such as high calcium, kidney damage, anemia, and bone lesions. While current risk-stratification models consider factors like tumor burden, cytogenetic abnormalities, and the presence of plasma cell leukemia or extramedullary disease, these tools do not account for how quickly patients respond to modern treatments.

The statement defines FHR multiple myeloma as disease that progresses within 18 months of starting first-line therapy, even in patients without high-risk cytogenetics. Early progression in these patients signals an aggressive disease biology and predicts shorter overall survival. The report highlights the importance of using depth and duration of response to novel induction therapies as dynamic indicators of risk. It also outlines potential strategies to better identify and manage FHR patients, aiming to improve outcomes in this challenging subgroup.
 

 

"Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies"

Source

Techaapornkun, P., Rojpalakorn, W., Mejun, N. et al. Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06524-6  September 9, 2025. 

Overview

This consensus statement focuses on a subset of multiple myeloma patients known as functional high-risk (FHR), who experience early disease progression despite initially appearing to have standard-risk disease. Multiple myeloma is a blood cancer marked by excess plasma cells in the bone marrow and complications such as high calcium, kidney damage, anemia, and bone lesions. While current risk-stratification models consider factors like tumor burden, cytogenetic abnormalities, and the presence of plasma cell leukemia or extramedullary disease, these tools do not account for how quickly patients respond to modern treatments.

The statement defines FHR multiple myeloma as disease that progresses within 18 months of starting first-line therapy, even in patients without high-risk cytogenetics. Early progression in these patients signals an aggressive disease biology and predicts shorter overall survival. The report highlights the importance of using depth and duration of response to novel induction therapies as dynamic indicators of risk. It also outlines potential strategies to better identify and manage FHR patients, aiming to improve outcomes in this challenging subgroup.
 

 

"Prognostic impact of focal lesion location and persistence in multiple myeloma: insights from serial PET/DWI imaging"

Source

Carolina Schinke, Leo Rasche, Cody Ashby, Rudy van Hemert, Sharmilan Thanendrarajan, Samer Al Hadidi, Maurizio Zangari, Clyde Bailey, Daisy V. Alapat, John D. Shaughnessy, Fenghuang Zhan, Bart Barlogie, Frits van Rhee, Niels Weinhold; Prognostic impact of focal lesion location and persistence in multiple myeloma: insights from serial PET/DWI imaging. Blood Adv 2025; 9 (17): 4368–4377. doi: https://doi.org/10.1182/bloodadvances.2025016510  September 9, 2025. 

Overview

This study explored how focal lesions (FLs)—dense clusters of myeloma cells in the bone marrow—affect outcomes in multiple myeloma. Researchers analyzed PET and diffusion-weighted MRI scans from 243 patients at diagnosis, after autologous stem cell transplant (ASCT), and regularly during follow-up. They found that FLs in the long bones, such as the humerus or femur, were linked to poorer prognosis. Residual FLs detected after ASCT, though uncommon on PET scans, also predicted worse outcomes, while one-third of patients showed persistent FLs on MRI, which similarly indicated higher risk.

Even when FLs resolved after a second ASCT, their prior presence still carried negative prognostic significance, highlighting the limits of late imaging in high-risk patients. The best outcomes were seen in patients who achieved both minimal residual disease (MRD) negativity and imaging negativity. However, MRD-negative patients with residual FLs had similarly poor outcomes as those positive on both measures. Persistent FLs at relapse were often found at the same or nearby sites as previous lesions, suggesting resistant disease that standard imaging may not fully detect. Overall, the findings emphasize the prognostic importance of long bone FLs, the value of serial imaging, and the need for alternative therapies for patients with persistent lesions.

 

 

"Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia"

Source

Andrew R. Branagan, Clifton Mo, Matthew Lei, Joshua N. Gustine, Andrew J. Yee, Elizabeth O’Donnell, Jorge J. Castillo, Omar Nadeem, Catherine Flynn, Zachary Bernstein, Rie Nakamoto-Matsubara, Kirsten Meid, Rakesh Verma, Zachary R. Hunter, Maria L. Guerrera, Galit Alter, Jill Burke, Cynthia Harrington, Emerentia Agyemang, Marilyn Gammon, Kathleen Lively, Lisette Packer, Nora Horick, Jacob Laubach, Constantine S. Mitsiades, Nikhil Munshi, Kenneth C. Anderson, Steven P. Treon, Paul G. Richardson, Noopur S. Raje, Shayna R. Sarosiek; Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia. Blood Adv 2025; 9 (18): 4568–4579. doi: https://doi.org/10.1182/bloodadvances.2025016513   September 10, 2025. 

Overview

This study examined how patients with multiple myeloma (MM) and Waldenström macroglobulinemia (WM) respond to COVID-19 vaccination. Both groups are at higher risk for severe COVID-19 and often have weaker immune responses to vaccines. Researchers followed 93 patients with MM and 48 with WM, measuring their antibody responses after the primary vaccination series and subsequent booster doses. After the initial series, only 47% of MM patients and 25% of WM patients developed a strong antibody response. However, booster vaccinations significantly improved immunity, raising response rates to 84% and 91% in MM patients and 60% and 89% in WM patients after the first and second boosters, respectively.

The study also identified factors linked to weaker responses. In MM patients, low immunoglobulin levels, low lymphocyte counts, and treatments with anti-CD38 antibodies or corticosteroids reduced vaccine effectiveness. In WM, Bruton tyrosine kinase inhibitors or rituximab were associated with lower responses, while treatment-naïve patients had stronger responses. Functional testing showed that antibody activity against SARS-CoV-2, including variants, was lower in both patient groups compared with healthy donors. Overall, the findings show that while MM and WM patients have impaired responses to the initial COVID-19 vaccines, booster doses can substantially enhance immunity.

 

 

 

"Evaluation of Proteinuria in Plasma Cell Disorders: Shortcomings of Measurements Based on 24-Hour Collections and Alternative Approaches"

Source

Glen L Hortin, John M Koomen, Evaluation of Proteinuria in Plasma Cell Disorders: Shortcomings of Measurements Based on 24-Hour Collections and Alternative Approaches, The Journal of Applied Laboratory Medicine, 2025;, jfaf130, https://doi.org/10.1093/jalm/jfaf130  September 10, 2025.  

Overview

This review focuses on how urinary protein and free light chain measurements are used to diagnose and monitor clonal plasma cell disorders like multiple myeloma. Traditionally, these tests rely on 24-hour urine collections, which are burdensome for patients, prone to errors, and slow to produce results. These limitations have prompted interest in alternative approaches that are simpler and more efficient.

One promising method is estimating 24-hour protein excretion from a single spot urine sample using the protein-to-creatinine ratio. Random urine samples may also be sufficient for detecting the presence of monoclonal free light chains, which are important both for diagnosis and for monitoring response to therapy. Overall, the evidence suggests that spot urine testing could replace the traditional 24-hour collection, making evaluation faster and more convenient, though further studies and guideline updates are needed to support widespread adoption.

 

 

"An Italian real-world multicenter study of patients with refractory/relapsed functional high-risk multiple myeloma patients treated with second-line therapies"

Source

De Novellis, D., Palmieri, S., Rocco, S. et al. An Italian real-world multicenter study of patients with refractory/relapsed functional high-risk multiple myeloma patients treated with second-line therapies. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06572-y September 10, 2025. 

Overview

This study examined outcomes in patients with functional high-risk multiple myeloma (FHRMM), a group that experiences early relapse and poor survival despite initial therapy. Researchers analyzed 62 patients who either received a first-line daratumumab-based quadruplet regimen or relapsed within 12 months after autologous stem cell transplant (ASCT). The overall response rate to second-line therapy was 61%, with 42% achieving a very good partial response or better. At 12 months, an estimated 54% of patients remained progression-free, and 72% were alive.

Certain factors were linked to poorer outcomes, including extramedullary disease, prior lenalidomide maintenance, lack of ASCT consolidation, advanced disease stage, higher ECOG scores, and salvage therapy without carfilzomib-lenalidomide-dexamethasone. Carfilzomib-based regimens showed some benefit, particularly in patients who had not previously received lenalidomide, but overall outcomes remained suboptimal. The study highlights the challenges of managing FHRMM in the absence of standardized guidelines and suggests that earlier use of novel therapies may improve outcomes. Larger prospective trials are needed to define optimal strategies for this high-risk population.

 

 

"Plasmapheresis facilitates soluble BCMA clearance and contributes to reversing primary resistance to anti-BCMA immunotherapy in multiple myeloma"

Source

Neubert, S., Munawar, U., Mersi, J. et al. Plasmapheresis facilitates soluble BCMA clearance and contributes to reversing primary resistance to anti-BCMA immunotherapy in multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02757-6  September 10, 2025.  

Overview

This study examined outcomes in patients with functional high-risk multiple myeloma (FHRMM), a group that experiences early relapse and poor survival despite initial therapy. Researchers analyzed 62 patients who either received a first-line daratumumab-based quadruplet regimen or relapsed within 12 months after autologous stem cell transplant (ASCT). The overall response rate to second-line therapy was 61%, with 42% achieving a very good partial response or better. At 12 months, an estimated 54% of patients remained progression-free, and 72% were alive.

Certain factors were linked to poorer outcomes, including extramedullary disease, prior lenalidomide maintenance, lack of ASCT consolidation, advanced disease stage, higher ECOG scores, and salvage therapy without carfilzomib-lenalidomide-dexamethasone. Carfilzomib-based regimens showed some benefit, particularly in patients who had not previously received lenalidomide, but overall outcomes remained suboptimal. The study highlights the challenges of managing FHRMM in the absence of standardized guidelines and suggests that earlier use of novel therapies may improve outcomes. Larger prospective trials are needed to define optimal strategies for this high-risk population.

 

 

"From Trials to Practice: A 2025 Review of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel Efficacy Across Clinical Studies and Real-World Evidence"

Source

H. G. Pleitez, S. Saowapa, A. O. Maldonado, C. Kanitthamniyom, D. O. Bernal, and L. Tijani, “From Trials to Practice: A 2025 Review of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel Efficacy Across Clinical Studies and Real-World Evidence,” European Journal of Haematology (2025): 1–14, https://doi.org/10.1111/ejh.70025.  September 10, 2025

Overview

BCMA-directed CAR T-cell therapies have transformed treatment for relapsed or refractory multiple myeloma (RRMM). As of 2025, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are the only FDA-approved BCMA CAR T therapies. Clinical trials have shown remarkable results even in heavily pretreated patients, with overall response rates of 73% in the KarMMa-1 trial and 98% in CARTITUDE-1. These therapies also improve progression-free survival compared to standard regimens, especially when used earlier in the treatment course.

Real-world data confirm that CAR T-cell therapy is effective and generally safe across a broader patient population, including individuals who would not have qualified for clinical trials. Key side effects include cytokine release syndrome and neurotoxicity, with emerging concerns about delayed neurological effects, second primary cancers, and immune-mediated gastrointestinal issues. Overall, these therapies are reshaping the myeloma treatment landscape, though challenges remain regarding accessibility, long-term safety, and optimizing outcomes. The review highlights the need for continued research to refine their use and maximize patient benefit.

 

 

"Evaluation of ambulatory use of daratumumab hyaluronidase injection"

Source

Vannarat N, Hermel DJ, Spengler AM. Evaluation of ambulatory use of daratumumab hyaluronidase injection. Journal of Oncology Pharmacy Practice. 2025;0(0). doi:10.1177/10781552251374914 September 10, 2025. 

Overview

This study examined the safety of subcutaneous daratumumab (Dara SC) in patients with multiple myeloma and light chain amyloidosis when given in an outpatient setting. Dara SC targets CD38 on plasma cells and offers the benefit of shorter administration times compared with intravenous daratumumab, but optimal post-injection monitoring remains unclear. Researchers reviewed 97 patients who received their first three doses of Dara SC, tracking infusion- and injection-related reactions.

The overall incidence of reactions was low, with 7% experiencing infusion-related reactions and 2% experiencing injection-site reactions. Most reactions were mild (Grade 1), with only one Grade 2 reaction reported. Infusion-related reactions occurred exclusively with the first dose, while injection-site reactions appeared with the second and third doses. No reactions were observed in patients already experienced with daratumumab. The findings suggest that Dara SC is generally safe and well-tolerated in the outpatient setting, and intensive monitoring protocols may not be necessary, as reactions were mild, reversible, and required minimal supportive care.

 

 

"Tumultuous Development of Venetoclax in t(11;14) Multiple Myeloma"

Source

Martin F. Kaiser et al. Tumultuous Development of Venetoclax in t(11;14) Multiple Myeloma. JCO 0, JCO-25-01088 DOI:10.1200/JCO-25-01088  September 10, 2025. 

Overview

This review examines the development and clinical journey of venetoclax, a BCL2 inhibitor, in multiple myeloma patients with the t(11;14) translocation. Early preclinical studies and phase I trials showed that venetoclax selectively induced apoptosis in t(11;14) myeloma cells, suggesting a promising targeted therapy for this biologically distinct subgroup. However, subsequent phase III trials, including BELLINI and CANOVA, faced significant challenges. BELLINI tested venetoclax in all-comer relapsed/refractory myeloma, leading to unexpected safety concerns, particularly fatal infections in non-t(11;14) patients, and delayed regulatory approval. CANOVA later focused exclusively on t(11;14) myeloma, but venetoclax-dexamethasone did not demonstrate superior progression-free survival compared with pomalidomide-dexamethasone, again limiting formal approval.

The authors highlight how trial design decisions, regulatory requirements, and limited global access to molecular diagnostics restricted patient availability for this targeted therapy. Despite these hurdles, clinical experience and off-label use suggest venetoclax benefits some patients with t(11;14) myeloma and related plasma cell disorders. The paper emphasizes the need for regulatory frameworks that adapt to molecularly defined subgroups, careful trial design, and strategies to optimize patient selection, dosing, and combination therapies. It also notes the potential of newer BCL2 inhibitors, such as sonrotoclax and lisaftoclax, to address unmet needs in this rare myeloma population.

 

 

"Efficacy and safety of BCMA nanobody CAR T-cell therapy in relapsed or refractory plasma cell myeloma"

Source

Xian G. Zhang, Lin Wang, Junfang Yang, Xiaona N. Hu, Hui Wang, Lina N. Zhang, Xiaoge Zhou, Ying Liu, Qinglong Wang, Peihua H. Lu; Efficacy and safety of BCMA nanobody CAR T-cell therapy in relapsed or refractory plasma cell myeloma. Blood Adv 2025; 9 (18): 4543–4552. doi: https://doi.org/10.1182/bloodadvances.2025016322  September 10, 2025.  

Overview

This study evaluates a novel BCMA-targeted CAR T-cell therapy using dual-nanobody variable heavy chain domains (VHHs) in patients with relapsed or refractory (R/R) plasma cell myeloma, including high-risk subgroups. Twenty-seven patients, some with plasma cell leukemia, anaplastic plasma cell myeloma, extramedullary disease, or high-risk genetic abnormalities (including TP53 mutations), received the nanobody-based S103 CAR T-cell therapy. One month after infusion, the overall response rate (ORR) was 96.3%, with 59.2% achieving complete or very good partial responses (CR + VGPR). By three months, the ORR reached 100%, with 81.5% achieving CR + VGPR. The median duration of remission was 11 months, while 1-year overall survival and progression-free survival rates were 61.1% and 57.2%, respectively.

The findings demonstrate that dual-nanobody BCMA CAR T-cell therapy offers a high response rate and manageable safety profile, even in patients with aggressive or high-risk disease features. This trial supports further investigation of nanobody-based CAR constructs as a promising therapeutic option for challenging R/R multiple myeloma populations.

 

 

"Racial disparities in multiple myeloma"

Source

Erius Tebuka, Peter Rambau, Leo Rasche; Racial disparities in multiple myeloma. Blood Global Hematology 2025; 1 (2): 100017. doi: https://doi.org/10.1016/j.bglo.2025.100017  September 10, 2025.   

Overview

This review examines racial disparities in multiple myeloma (MM), focusing on differences between Black (African descent) and White (European descent) patients in disease incidence, biology, clinical presentation, treatment, and survival. Black individuals have a higher prevalence of MGUS, the precursor to MM, and are diagnosed at a younger age, yet disease progression rates are similar between races. Clinical presentations also differ: Black patients are more likely to have anemia, renal dysfunction, extramedullary disease, and high-risk MM features, while delays in diagnosis and treatment contribute to poorer outcomes.

Biological differences include variations in B-cell responses, immunoglobulin subtypes, and tumor mutation patterns. Black patients show distinct cytogenetic profiles, lower frequencies of high-risk mutations such as TP53 deletions, and differences in MM risk loci. Familial clustering of MM is more pronounced in Black populations, further highlighting inherited susceptibility.

Despite higher MM incidence, real-world data suggest overall survival is similar or even superior in Black patients when treatment access is equalized, particularly for those receiving stem cell transplants or novel therapies. The review concludes that improving access to approved therapies, clinical trials, and equitable healthcare delivery is essential to eliminate racial disparities in MM outcomes, and recommends prioritizing diversity and inclusion in trial design and capacity building in African countries.
 

 

"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 Karl Mai, Sandra Sauer, Raphael Teipel, Malte von Bonin, Michael Hallek, Christof Scheid, Philipp Gödel; Sequential BCMA CAR T-cell therapy in refractory multiple myeloma. Blood Adv 2025; 9 (18): 4624–4630. doi: https://doi.org/10.1182/bloodadvances.2025016712 September 11, 2025.   

Overview

This study explores the safety and effectiveness of sequential BCMA-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma (RRMM) who progressed after initial treatment. Ten heavily pretreated patients first received idecabtagene vicleucel and, upon relapse, were treated with ciltacabtagene autoleucel. Bridging therapies were allowed between treatments. Sequential CAR T-cell therapy was well tolerated, with no new safety concerns or higher-grade immune-related side effects. The second infusion produced strong CAR T-cell expansion and high response rates: all patients achieved at least a very good partial response, 60% reached minimal residual disease negativity, and estimated six-month progression-free survival was 64.8%. Patients with longer responses to the first CAR T-cell therapy tended to have more durable responses to the second. Loss of BCMA antigen was rare, occurring in only one of three patients relapsing after the second infusion. These findings provide the first real-world evidence that using two different commercially approved BCMA CAR T-cell products sequentially is feasible and effective, particularly for patients who initially respond well.

 

 

"Influence of Chimeric Antigen Receptor T-Cell Therapy on Fracture Risk of Patients With Multiple Myeloma"

Source

Huynh, Thien Huong N. BS; Clampitt, Bryan A. BS; Chose, Chloe M. BS; Nester, Matthew D. BS; Joyce, David M. MD; Binitie, Odion T. MD; Freeman, Ciara L. MD; Lazarides, Alexander L. MD. Influence of Chimeric Antigen Receptor T-Cell Therapy on Fracture Risk of Patients With Multiple Myeloma. Journal of the American Academy of Orthopaedic Surgeons ():10.5435/JAAOS-D-25-00392, September 11, 2025. | DOI: 10.5435/JAAOS-D-25-00392. 

Overview

This study examined how CAR-T therapy affects fracture risk in patients with relapsed or refractory multiple myeloma, a population often burdened with skeletal lesions. Researchers retrospectively reviewed 139 patients who had PET-CT scans before CAR-T infusion and at least one follow-up scan at 90 days or later. Before therapy, 37 patients (28%) were considered at risk for pathologic fracture. After CAR-T treatment, only three patients (2.5%) remained at risk, representing a significant reduction. PET-CT analysis showed that initially high-risk lesions had higher standardized uptake values, but post-CAR-T, differences between at-risk and low-risk lesions were no longer observed. Three fractures occurred after treatment, and 33 patients (24%) died at a mean of 6.6 months. These findings suggest that CAR-T therapy not only targets multiple myeloma effectively but may also reduce the risk of pathologic fractures, offering an added clinical benefit for patients with skeletal disease.

 

 

"Trends in mortality of renal failure in adult multiple myeloma patients: a CDC data analysis (1999–2020)"

Source

Shahid, H., Haseeb, A., Iftikhar, A. et al. Trends in mortality of renal failure in adult multiple myeloma patients: a CDC data analysis (1999–2020). Int Urol Nephrol (2025). https://doi.org/10.1007/s11255-025-04788-5 September 11, 2025. 

Overview

This study analyzed two decades of U.S. national mortality data to understand trends and disparities in deaths from multiple myeloma (MM) complicated by renal failure. Using the CDC WONDER database, researchers examined adults aged 25 and older who had both MM and renal failure listed as causes of death. From 1999 to 2020, overall mortality initially rose, particularly among men, White patients, and those in the Midwest and South, before declining across all demographic and geographic groups. The age-adjusted mortality rate fell from 1.26 per 100,000 in 1999 to 1.02 per 100,000 in 2020. Men saw rates rise until 2005 before a sharp decline, while women experienced an increase only until 2002, followed by steady decreases. Asian, Black, and Hispanic populations showed consistent declines from 1999 onward, while White populations initially rose before decreasing. Regional trends mirrored these patterns, with early increases in the Midwest and South and steady declines in the Northeast and West. These findings highlight that while mortality from MM-related renal failure has improved overall, early rises in specific populations underscore the need for targeted interventions to reduce renal-related deaths in high-risk patients.
 

 

 

"NAT10 contributes to the progression of multiple myeloma through ac4C modification of GPR37"

Source

Liu, H., Zhang, X., Lu, Q., & Zhang, H. (2025). NAT10 contributes to the progression of multiple myeloma through ac4C modification of GPR37. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2555779  September 11, 2025. 

Overview

This study explored the role of NAT10, an enzyme that modifies mRNA through acetylation, in multiple myeloma (MM). Researchers found that GPR37, a G protein-coupled receptor, is highly expressed in MM cells and patient samples. Reducing GPR37 levels in MM cells slowed cell growth, disrupted the cell cycle, reduced glycolysis, limited immune evasion, and promoted cell death in laboratory experiments. Further investigation revealed that NAT10 increases GPR37 expression by modifying its mRNA, enhancing its stability. When NAT10 was reduced, MM cells showed similar effects to GPR37 knockdown: slower growth, impaired metabolism, increased apoptosis, and reduced tumor growth in mouse models. These findings suggest that NAT10 drives MM progression by regulating GPR37, highlighting both NAT10 and GPR37 as promising targets for future MM therapies.
 

 

 

"Use of Hospital-at-Home Services for Injectable Chemotherapy for Patients With Multiple Myeloma in France in 2019 and 2020: A Real-World Nationwide Study Based on the French Hospital Discharge Database"

Source

L. Vincent, A.-S. Jannot, H. Mechiche, U. Rodts, and G. Désaméricq, “Use of Hospital-at-Home Services for Injectable Chemotherapy for Patients With Multiple Myeloma in France in 2019 and 2020: A Real-World Nationwide Study Based on the French Hospital Discharge Database.” eJHaem 6, no. 5 (2025): e70144. https://doi.org/10.1002/jha2.70144 September 11, 2025.  

Overview

This study looked at adults with multiple myeloma (MM) in metropolitan France who received injectable chemotherapy either at home through hospital-at-home (HAH) services or in outpatient hospital units (OHUs) during 2019–2020. Out of 9,278 patients, 23% received at least one HAH injection. Patients using HAH tended to be diagnosed more recently, lived in larger and wealthier cities, and were closer to their treating hospital compared with those treated only in OHUs. Receiving bortezomib or carfilzomib, or starting chemotherapy in 2020, were the strongest factors linked to HAH use. HAH administration increased between 2019 and 2020, likely due to the COVID-19 pandemic, but overall use remained limited and varied by region. Hospitalizations for infections stayed stable. These findings show that home-based chemotherapy is safe and feasible, but wider and more equitable access could further improve patient quality of life and help reduce healthcare costs.

 

 

"PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism"

Source

Oudaert, I., van den Broecke, L., Aksoy, O., Lind, J., Vallet, S., Van der Vreken, A., Ates, G., Massie, A., Maes, K., De Veirman, K., De Bruyne, E., Vanderkerken, K., Podar, K. and Menu, E. (2025), PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism. Mol Oncol. https://doi.org/10.1002/1878-0261.70120  September 11, 2025. 

Overview

This study explored how bone marrow stromal cells (BMSCs) influence multiple myeloma (MM) progression and treatment resistance. Researchers focused on PYCR1, an enzyme involved in proline synthesis that is highly expressed in BMSCs. When MM cells were cultured with medium from PYCR1-silenced BMSCs, their energy production through oxidative phosphorylation was impaired, making them more sensitive to Velcade® (bortezomib). Further analysis showed that PYCR1 inhibition reduced the release of activin A, a factor that supports MM cell survival. Adding back proline or activin A reversed this increased drug sensitivity. In models combining the PYCR1 inhibitor pargyline with bortezomib, tumor burden decreased, and serum activin A levels dropped in mice. These results highlight that targeting stromal cell metabolism, specifically PYCR1 in BMSCs, can limit MM cell energy production, reduce activin A signaling, and enhance the effectiveness of bortezomib therapy.

 

 

"The mitochondrial protease ClpP is a metabolic vulnerability and an immunogenic trigger against multiple myeloma"

Source

Tommaso Perini, Paola Zordan, Rossella Del Pizzo, Massimo Resnati, Lisa Viviani, Davide Stefanoni, Laura Cassina, Ugo Orfanelli, Matteo Trudu, Laura Oliva, Daniel Lacidogna, Mehmet K. Samur, Maria Materozzi, Denise Drago, Annapaola Andolfo, Marco Patrone, Massimo Degano, Alessandra Boletta, Enrico Milan, Fabio Ciceri, Nikhil C. Munshi, Matteo Bellone, Simone Cenci; The mitochondrial protease ClpP is a metabolic vulnerability and an immunogenic trigger against multiple myeloma. Blood 2025; 146 (11): 1286–1299. doi: https://doi.org/10.1182/blood.2024026340  September 11, 2025.  

Overview

This study explored a new vulnerability in multiple myeloma (MM) by targeting the mitochondrial protease ClpP. Researchers found that ClpP is highly expressed in malignant plasma cells and that MM cells are especially dependent on it for survival. ClpP supports MM cell growth by regulating ornithine aminotransferase, which is essential for producing polyamines needed for cancer cell metabolism. Inhibiting ClpP not only disrupted MM cell metabolism but also activated an immune response: it triggered a type I interferon pathway, enhanced dendritic cell activity, and increased T-cell production of IFN-γ. In mice, ClpP silencing reshaped the bone marrow immune environment, expanding protective T cells while limiting exhausted T cells and suppressive myeloid cells. These findings show that ClpP is both a metabolic Achilles’ heel for MM cells and a way to stimulate antitumor immunity, offering a promising dual strategy for therapy.
 

 

 

"ClpP: a new Achilles' heel in myeloma"

Source

Antonio Sacco, Aldo M. Roccaro; ClpP: a new Achilles' heel in myeloma. Blood 2025; 146 (11): 1254–1255. doi: https://doi.org/10.1182/blood.2025029682  September 11, 2025.  

Overview

This commentary highlights a major discovery in multiple myeloma (MM) therapy: the mitochondrial protease ClpP is a key vulnerability in MM, acting both as a metabolic dependency and as a trigger for immune activation. Researchers found that ClpP is highly expressed in MM plasma cells compared with normal or premalignant cells, and MM cell lines show the highest ClpP levels among cancers. Rather than simply maintaining mitochondrial function, ClpP controls ornithine aminotransferase, supporting polyamine production that MM cells need to grow.

Blocking ClpP kills MM cells directly and also sparks an immune response. ClpP inhibition activates the cGAS-STING pathway, triggering type I interferon signaling, priming dendritic cells, and boosting T-cell activity. In mouse models, this reshapes the bone marrow immune environment, expanding interferon-γ–producing and memory T cells while reducing exhausted T cells and suppressive myeloid cells. This suggests that targeting ClpP can both kill MM cells and turn the normally quiet myeloma niche into an immune-active site.

Future studies should investigate how ClpP is regulated in MM, its role in disease progression, and how ClpP-directed therapies can best be integrated with immune-based treatments. This dual-action approach positions ClpP as a promising therapeutic target that could reshape MM treatment strategies.

 

 

"Venetoclax bei r/rMM eher ungeeignet"

Source

Müller, T. Venetoclax bei r/rMM eher ungeeignet. InFo Hämatol Onkol 28, 32 (2025). https://doi.org/10.1007/s15004-025-1080-0 September 11, 2025.  

Overview

The final results of the phase III BELLINI study confirm that adding venetoclax to Velcade® (bortezomib) and dexamethasone in relapsed or refractory multiple myeloma (r/rMM) improves response in some patients but is linked to increased overall mortality. The trial enrolled 291 adults who had received one to three prior therapies and were either naive or sensitive to proteasome inhibitors. All patients received bortezomib and dexamethasone; two-thirds also received venetoclax, a Bcl2 inhibitor, while the rest received placebo, with a median follow-up of nearly 46 months.

Patients treated with venetoclax experienced a longer median progression-free survival (23.4 vs. 11.4 months) and higher overall response rates (84% vs. 70%) compared with placebo. However, overall survival was worse in the venetoclax group, with 40% of patients dying versus 37% in the control group, representing a 19% increase in mortality over the study period, though this was not statistically significant.

Subgroup analyses suggested potential benefits in patients with the t(11;14) translocation and those with high Bcl2 expression. In these groups, mortality appeared lower—by 41% and one-third, respectively—but numbers were small and findings were not statistically significant. The study concludes that venetoclax should not be used broadly in r/rMM but may be appropriate for carefully selected patients with t(11;14) or high Bcl2 expression.
 

 

 

"Monoterpenoid fluorophthalimide IMiDs that lack human cereblon binding: synthesis and anti-proliferative, anti-angiogenic and anti-inflammatory activities"

Source

Weiming Luo, Kathleen M. Garchitorena, David Tweedie, Cindy H. Chau, Chirag N. Patel, Maxime A. Siegler, Neil Vargesson, Inho Hwang, Soyeon Kim, Dong Seok Kim, William D. Figg, Nigel H. Greig, Monoterpenoid fluorophthalimide IMiDs that lack human cereblon binding: synthesis and anti-proliferative, anti-angiogenic and anti-inflammatory activities, Biochemical and Biophysical Research Communications, Volume 779, 2025, 152428, ISSN 0006-291X, https://doi.org/10.1016/j.bbrc.2025.152428. September 12, 2025.   

Overview

New research explores next-generation immunomodulatory drugs (IMiDs) designed to overcome resistance in multiple myeloma (MM). Traditional IMiDs, built on the thalidomide backbone, rely on cereblon—a key protein in the E3 ubiquitin ligase complex—to degrade neosubstrates that drive their anticancer and anti-inflammatory effects. Over time, cancer cells can downregulate cereblon, leading to acquired resistance and inevitable relapse.

Researchers developed novel IMiD analogues by modifying the thalidomide structure: a monoterpenoid group replaced the classic glutarimide to prevent cereblon binding, and polyfluorination of the phthalimide ring enhanced activity. These new compounds showed strong anti-proliferative effects against both lenalidomide-sensitive and lenalidomide-resistant MM cell lines, while also exhibiting anti-angiogenic and anti-inflammatory effects through cereblon-independent mechanisms.

Cellular studies confirmed the activity of four lead compounds in MM cells, human endothelial cells, and mouse macrophages. These findings highlight a promising new class of cereblon-independent IMiDs that may offer effective treatment options for patients with resistant MM and other inflammatory conditions.
 

 

 

"mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow"

Source

Taylor Fulton-Ward, Nancy Gudgeon, Isaac Thirlwell, Emma Louise Bishop, Bryan Marzullo, Hannah Victoria Giles, Graham McIlroy, Paul Ferguson, Bhuvan Kishore, Kate Rogers, Nuri Nuri Alfasi, Timothy Wong, Satnam Aytain, Daniel A. Tennant, Guy Pratt, Sarah Dimeloe; mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow. Blood Adv 2025; bloodadvances.2025016439. doi: https://doi.org/10.1182/bloodadvances.2025016439 September 12, 2025    

Overview

New research shows that low oxygen levels in the bone marrow can limit the effectiveness of T cell–based therapies in multiple myeloma (MM). CD8+ T cells exposed to hypoxia showed reduced activation, proliferation, and interferon-gamma (IFN-γ) production, while cytotoxicity and tumor necrosis factor-alpha (TNF-α) remained unchanged. These functional changes were linked to decreased mTOR activity and lower c-Myc expression, both key drivers of T cell metabolic reprogramming.

Under hypoxia, CD8+ T cells had impaired glycolysis and mitochondrial glutamine oxidation, driven by higher BNIP3 levels and reduced Rheb, an important mTOR activator. Testing BCMAxCD3 bispecific antibodies confirmed that hypoxia blunted T cell activation, IFN-γ production, proliferation, and memory differentiation, though initial tumor killing was preserved. Analysis of bone marrow CD8+ T cells from MM patients mirrored these findings, showing lower c-Myc and Rheb levels and higher BNIP3 compared to peripheral blood cells.

These results suggest that the hypoxic bone marrow environment may limit the full potential of T cell–directed therapies, highlighting the need for strategies that overcome hypoxia-induced suppression to improve treatment outcomes in MM.
 

 

 

"In Vitro Evaluation of Bortezomib-Loaded Superparamagnetic Iron Oxide Nanoparticles for Multiple Myeloma Cells Under Guide-Targeted Variable Magnetic Fields"

Source

Gül Kozalak, Ali Koşar, In Vitro Evaluation of Bortezomib-Loaded Superparamagnetic Iron Oxide Nanoparticles for Multiple Myeloma Cells Under Guide-Targeted Variable Magnetic Fields, ChemNanoMat 2025, 0, e202500225. https://doi.org/10.1002/cnma.202500225 September 12, 2025.    

Overview

Researchers are developing a new approach to make bortezomib treatment for multiple myeloma (MM) safer and more effective. While bortezomib is a key therapy, it often causes side effects like peripheral neuropathy and thrombocytopenia, and long-term use can lead to drug resistance. This study explores using superparamagnetic iron oxide nanoparticles (SPIONs) as a targeted drug delivery system. Bortezomib is loaded onto SPIONs, which release the drug specifically in the acidic environment of cancer cell vacuoles.

In lab tests, this targeted approach inhibited MM cell growth more effectively than the same dose of free bortezomib. Researchers also applied a variable magnetic field to guide the SPIONs, which further boosted their cancer-killing effects. Mechanistic studies showed shifts in apoptosis-related proteins, indicating that the therapy promotes programmed cell death. This method allows lower doses of bortezomib to be used while minimizing side effects, offering a promising new strategy not only for MM but potentially for other cancers as well.

 

 

 

"Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma"

Source

Zhibo Yan, Zhannan Han, Yihui Wang, Maja Beus, Yu Zhang, Alfredo Picado, Carrow I. Wells, Jian Wu, Loren B. Weidenhammer, Karla M. Pires, Elizabeth A. Leibold, Liang Liu, David M. Gooden, Ivan Spasojevic, Erik Soderblom, Yubin Kang, Lawrence H Boise, Timothy M. Willson, Mikhail A. Nikiforov; Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma. Blood 2025; blood.2025029950. doi: https://doi.org/10.1182/blood.2025029950 September 12, 2025.    

Overview

Researchers have identified a key mechanism that helps multiple myeloma (MM) cells survive and resist treatment. MM progression is often linked to suppression of ferroptosis, a type of cell death driven by iron-dependent lipid damage. This study found that the kinase STK17B acts as a major suppressor of ferroptosis in MM. Higher STK17B levels are associated with worse survival and are especially elevated in relapsed cases.

Blocking STK17B in MM cells increased iron levels, promoted lipid peroxidation, and made the cells more sensitive to standard therapies. An orally available STK17B inhibitor induced ferroptosis and significantly reduced tumor growth in mouse models. Mechanistic studies revealed that STK17B directly modifies IREB2 and HSPB1, key regulators of iron uptake and storage, and indirectly maintains STAT3 activation, further suppressing ferroptosis. These findings highlight a clinically relevant STK17B signaling pathway that contributes to drug resistance and suggest that targeting STK17B could improve treatment outcomes in MM.
 

 

 

"The national and subnational burden of multiple myeloma (MM) in Italy from 1990 to 2023: results from the global burden of disease study 2023"

Source

Roberto Passera, Giulia Zamagni, Elisa Fabbro, Giulia Carreras, Caterina Ledda, Carlo La Vecchia, Lorenzo Giovanni Mantovani, Lorenzo Monasta, The national and subnational burden of multiple myeloma (MM) in Italy from 1990 to 2023: results from the global burden of disease study 2023, eClinicalMedicine, 2025, 103508, ISSN 2589-5370, https://doi.org/10.1016/j.eclinm.2025.103508. September 12, 2025.   

Overview

This study provides a detailed look at the burden of multiple myeloma (MM) in Italy from 1990 to 2023, revealing important national and regional trends. Using Global Burden of Disease (GBD) 2023 estimates, researchers assessed incidence, mortality, years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and the mortality-to-incidence ratio (MIR) across all 21 Italian regions.

In 2023, Italy recorded 6,700 new MM cases, 4,100 deaths, and 73,600 DALYs, with most of the burden driven by premature death (YLLs, 93.4%). Over the past three decades, the age-standardized incidence (ASIR) and mortality (ASMR) rates remained relatively stable nationally, while the MIR improved from 68.0 to 55.1, indicating better survival. Subnational analyses showed stability in incidence across all regions, with some improvements in mortality and DALYs, particularly in northern areas.

Compared to global and high-middle socio-demographic index (SDI) countries, Italy has higher MM incidence and mortality rates but shows more favorable trends in reducing deaths and DALYs over time. These findings highlight the positive impact of early diagnosis and modern therapies, while also underscoring geographic disparities in outcomes. Overall, the study emphasizes the importance of ongoing surveillance, equitable healthcare access, and targeted interventions to further reduce MM burden in Italy.
 

 

 

"Rational engineering of degradation tail-driven CELMoD–antibody conjugates for precision malignancy therapy"

Source

Yu Guo, Yi Song, Hanlin Wang, Yang Lu, Jingyu Zhang, Zheyuan Shen, Weijuan Kan, Yuxian Wang, Haiting Duan, Shuangshuang Geng, Bo Wang, Shaoting Li, Bizhi Li, Xi Chen, Shanshan Pei, Luo Fang, Jia Li, Yubo Zhou, Jinxin Che, Xiaowu Dong, Rational engineering of degradation tail-driven CELMoD–antibody conjugates for precision malignancy therapy, Acta Pharmaceutica Sinica B, 2025, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.09.009. September 12, 2025. 

Overview

This study explores a novel approach to treating multiple myeloma (MM) using degrader–antibody conjugates (DACs), a drug strategy designed to selectively eliminate cancer-causing proteins. Researchers focused on cereblon E3 ligase modulators (CELMoDs) to develop new DACs, inspired by prior success with IKZF1/3 degraders. By combining a modular library, neo-substrate screening, and conjugatable chemical modifications, they identified I034, a CELMoD payload with potent protein-degrading and anti-cancer activity at picomolar concentrations.

Using linker chemistry, I034 was attached to antibodies to create DACs, which showed superior safety and effectiveness compared to traditional auristatin-based conjugates in both cell studies and animal models. Notably, the CD38-targeting DAC, Dara-VA-I034, eradicated tumors at low doses. Mechanistic studies revealed that compatibility between the payload and the target antigen was critical, with CD38 conjugates showing positive feedback regulation. Overall, this research provides a rational framework for designing CELMoD-based DACs, offering a promising new strategy for MM and potentially other hematological cancers

 

 

 

"Hybrid Molecules of p53 Activators and Protoflavones to Target Multiple Myeloma"

Source

Francisca Lopes, Gábor Girst, Rafael Rincón, Ricardo J. F. Ferreira, Lídia M. Gonçalves, Lucília Saraiva, Hui-Chun Wang, Muriel Cuendet, Attila Hunyadi, Maria M. M. Santos, Hybrid Molecules of p53 Activators and Protoflavones to Target Multiple Myeloma, ChemMedChem 2025, 0, e202500600. https://doi.org/10.1002/cmdc.202500600 September 14, 2025. 

Overview

This study explores a new approach to treating multiple myeloma (MM) using hybrid compounds designed to attack the cancer through two complementary mechanisms: activating the p53 tumor-suppressor pathway and inhibiting the ATR protein, which is involved in DNA damage repair. The researchers first tested these compounds in colon and breast cancer cell lines to confirm their selectivity for the p53 pathway.

Next, the compounds were evaluated in multiple myeloma cell lines, including RPMI 8226 (mutant p53) and MM.1S (wild-type p53), to assess their ability to inhibit cancer cell growth. One compound, compound 15, was shown to block the DNA damage response triggered by doxorubicin through the ATR/Chk1 pathway, while leaving UV-induced responses unaffected. Overall, the hybrid compounds were more potent than their individual fragments, demonstrating lower IC50 values. These findings indicate that dual-action hybrid molecules could provide a promising new strategy for developing effective therapies against multiple myeloma.
 

 

 

"Glasgow Prognostic Score Serves as a Prognostic Factor of Clinical Outcome in Patients with Newly Diagnosed Multiple Myeloma"

Source

Li S, Zhang L, Liu S, Liang Z, Wang W, Wang Y, Liang Y. Glasgow Prognostic Score Serves as a Prognostic Factor of Clinical Outcome in Patients with Newly Diagnosed Multiple Myeloma. J Inflamm Res. 2025;18:12699-12711 https://doi.org/10.2147/JIR.S539706  September 13, 2025. 

Overview

This study examined the prognostic value of the Glasgow Prognostic Score (GPS), which reflects systemic inflammation through C-reactive protein and serum albumin levels, in patients with newly diagnosed multiple myeloma (NDMM). Researchers analyzed data from 865 NDMM patients, stratifying them by GPS and evaluating overall survival (OS) and progression-free survival (PFS).

The analysis revealed that higher GPS scores were strongly associated with worse OS and PFS. Even after adjusting for disease stage and other clinical factors, GPS remained an independent predictor of poor outcomes. Patients with elevated GPS also tended to have more advanced disease, as indicated by higher Durie-Salmon and International Staging System (ISS) classifications. Furthermore, GPS outperformed its modified versions (mGPS and Hs-mGPS) in prognostic accuracy. These findings suggest that GPS measured at diagnosis can provide valuable prognostic information and may serve as a useful tool for risk stratification in newly diagnosed multiple myeloma.
 

 

 

"Managing side effects of talquetamab for relapsed/ refractory multiple myeloma in MonumenTAL- 1: a plain language summary"

Source

Chari, A., Shenoy, S., Kruyswijk, S., Hilder, B., O’Rourke, L., & van de Donk, N. W. C. J. (2025). Managing side effects of talquetamab for relapsed/ refractory multiple myeloma in MonumenTAL- 1: a plain language summary. Future Oncology, 1–16. https://doi.org/10.1080/14796694.2025.2555170 September 15, 2025

Overview

This summary highlights the management of side effects in the MonumenTAL-1 clinical trial, which tested talquetamab in patients with relapsed or refractory multiple myeloma. In the study, over 70% of participants experienced improvement in their cancer or achieved undetectable disease, with some maintaining remission for months or years.

Some patients experienced side effects related to talquetamab, including oral issues, nail changes, skin reactions, infections, cytokine release syndrome, and immune effector cell–associated neurotoxicity syndrome (ICANS). Dose adjustments and modifications to the treatment schedule helped manage oral and nail side effects, while moisturizers and corticosteroids were effective for skin-related issues. Importantly, patients who altered their talquetamab dose generally continued to benefit from treatment similarly to those who did not. Most side effects resolved by study follow-up.

These findings emphasize that while talquetamab is effective in improving multiple myeloma, proactive management of side effects in collaboration with healthcare teams is essential for maintaining both safety and treatment benefits.
 

 

 

"A discrete choice experiment analysis to understand patient preferences for multiple myeloma treatments"

Source

Faiman B, Le HH, Laurent J, Patel S, Paner-Straseviciute A, Zhang X and Mikhael J (2025) A discrete choice experiment analysis to understand patient preferences for multiple myeloma treatments. Front. Oncol. 15:1628121. doi: 10.3389/fonc.2025.1628121 September 15, 2025. 

Overview

This study explored treatment preferences among adults with relapsed or refractory multiple myeloma (RRMM) in the U.S., focusing on what matters most when choosing therapies. A total of 149 patients completed an online survey between November 2023 and March 2024, which asked about key treatment features such as effectiveness and side effects. Most participants had received one to two prior lines of therapy, while smaller groups had three or more.

Results showed that patients strongly preferred treatments offering longer progression-free survival (PFS) and overall survival (OS), as well as higher overall response rates (ORR). Among side effects, patients were most concerned about cytokine release syndrome (CRS) and infections, while issues like nail or skin changes, hospitalization time, and taste disturbances were less important. Notably, patients indicated they would accept a high risk of CRS if it substantially increased treatment effectiveness.

These findings highlight that patients prioritize efficacy in RRMM therapy and emphasize the value of shared decision-making between patients and clinicians to align treatment choices with patient preferences.
 

 

 

"Dynamic Changes in Symptom Clusters and Symptom Networks in Patients With Multiple Myeloma: A Cross-lagged Network Analysis"

Source

Du, Huihui MS; Jiao, Qian MS; Liu, Chao BS; Wu, Xue PhD; Guo, Junyan PhD; Zheng, Hongjuan BS; Zhao, Lijie BS. Dynamic Changes in Symptom Clusters and Symptom Networks in Patients With Multiple Myeloma: A Cross-lagged Network Analysis. Cancer Nursing ():10.1097/NCC.0000000000001537, September 15, 2025. | DOI: 10.1097/NCC.0000000000001537  September 15, 2025.  

Overview

This study examined how symptoms change and interact over the course of chemotherapy in patients newly diagnosed with multiple myeloma (MM), aiming to guide more precise symptom management. A total of 175 patients completed the Memorial Symptom Assessment Scale at baseline and across the first four chemotherapy cycles. Researchers used factor analysis to identify symptom clusters and cross-lagged panel network analysis to uncover how symptoms predicted and influenced one another over time.

Four symptom clusters emerged: psychological distress, disease behavior, fatigue and lack of appetite, and abdominal distension with constipation. Early in treatment, feelings of irritability strongly predicted later difficulty falling asleep and nausea. In subsequent cycles, weight loss predicted fatigue, loss of appetite, and later psychological distress, while feeling nervous in later cycles predicted pain, loss of appetite, and low energy.

The study identified “irritability,” “nervousness,” and “weight loss” as key symptoms that drive changes across the symptom network. These findings highlight specific targets for nursing interventions, suggesting that addressing psychological tension and fatigue-related symptoms early may help reduce the overall symptom burden in MM patients undergoing chemotherapy.
 

 

 

"Cost-per-responder analysis of daratumumab, bortezomib, lenalidomide, and dexamethasone vs bortezomib, lenalidomide, and dexamethasone among transplant-eligible patients with newly diagnosed multiple myeloma"

Source

Gautam S, Morrison L, Thompson-Leduc P, Moore B, Wong G, Macomson B, Khare V, Gupta-Werner N, Medhekar R. Cost-per-responder analysis of daratumumab, bortezomib, lenalidomide, and dexamethasone vs bortezomib, lenalidomide, and dexamethasone among transplant-eligible patients with newly diagnosed multiple myeloma. J Manag Care Spec Pharm. 2025 Sep 15:1-10. doi: 10.18553/jmcp.2025.25142.   

Overview

This study examined the economic value of achieving and sustaining minimal residual disease (MRD)–negative status in transplant-eligible patients with newly diagnosed multiple myeloma (MM) using data from the phase 3 PERSEUS trial. The trial compared two first-line treatment approaches: daratumumab, bortezomib, lenalidomide, and dexamethasone followed by daratumumab maintenance (DVRd/DR) versus bortezomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance (VRd/R). Researchers developed a cost model from a U.S. mixed-payer perspective, including expenses for first- and second-line treatments, stem cell transplant, medical care, adverse event management, and MRD testing.

Results showed that at 48 months, the total cost per patient achieving MRD-negative status was significantly lower with DVRd/DR compared to VRd/R, with savings of $519,999 per patient. Key contributors to these savings included lower maintenance treatment costs and reduced need for second-line therapy, as fewer patients on DVRd/DR required additional treatment. Among patients who were MRD-positive after consolidation, DVRd/DR also led to lower costs per patient achieving sustained MRD negativity, with savings of $961,880 due to a higher conversion rate during maintenance.

These findings indicate that DVRd induction/consolidation followed by DR maintenance not only improves clinical outcomes but also provides substantial cost savings compared with VRd/R, highlighting both its efficacy and economic advantages in treating newly diagnosed, transplant-eligible MM patients.
 

 

 

"Tandem autologous hematopoietic stem cell transplantation in multiple myeloma: A historical perspective and current challenges"

Source

Wang, X., Cui, Y., Wang, Y. et al. Tandem autologous hematopoietic stem cell transplantation in multiple myeloma: A historical perspective and current challenges. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06563-z September 15, 2025.   

Overview

This review focuses on the role of hematopoietic stem cell transplantation in multiple myeloma (MM), particularly for newly diagnosed patients aged 70 years or younger who are eligible for autologous transplantation. For high-risk MM (HRMM) patients, studies suggest that tandem autologous hematopoietic stem cell transplantation (auto-HSCT) may provide significant benefits over a single auto-HSCT, notably in extending progression-free survival (PFS) and overall survival (OS). While allogeneic HSCT (allo-HSCT) offers the only potential for long-term cure, its use is limited by high transplant-related mortality and the risk of graft-versus-host disease.

The review also considers the impact of emerging therapies, including proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and CAR-T cell therapy, which are reshaping the MM treatment landscape and challenging the traditional role of tandem auto-HSCT. By critically examining the comparative efficacy of single versus tandem auto-HSCT and the potential role of sequential allo-HSCT, this analysis highlights both the clinical benefits and the evolving considerations for stem cell transplantation in modern MM therapy.
 

 

 

"Pseudohyperphosphatemia in multiple myeloma: removal of interfering paraproteins"

Source

De bruyn M, Cuykx M. Pseudohyperphosphatemia in multiple myeloma: removal of interfering paraproteins. Annals of Clinical Biochemistry. 2025;0(ja). doi:10.1177/00045632251383402  September 16, 2025    

Overview

This report highlights a laboratory artifact in multiple myeloma (MM) known as paraprotein-related pseudohyperphosphatemia. Some MM patients, particularly those with high IgG levels, may show falsely elevated serum phosphate when measured using the phosphomolybdate UV assay. This occurs because paraproteins interfere with the assay reaction, potentially leading to unnecessary clinical interventions.

In a case study, serum phosphate levels in a patient with IgG MM correlated with IgG concentrations, suggesting assay interference. Various methods were tested to remove the paraproteins, including dilution, protein precipitation with sulfosalicylic acid or zinc sulfate, and ultrafiltration. While precipitation reduced IgG levels, it did not reliably correct phosphate measurements. Only ultrafiltration successfully removed interfering proteins and produced accurate phosphate results.

This finding underscores the importance of recognizing pseudohyperphosphatemia in MM patients and using ultrafiltration to obtain reliable phosphate measurements, preventing unnecessary treatment decisions based on spurious laboratory results.
 

 

 

"Defining the Rates of Cytokine Release Syndrome Associated With Talquetamab Step-up Doses"

Source

Issam S. Hamadeh et al. Defining the Rates of Cytokine Release Syndrome Associated With Talquetamab Step-up Doses. JCO Oncol Pract 0, OP-25-00224 DOI:10.1200/OP-25-00224 September 16, 2025. 

Overview

This study evaluated cytokine release syndrome (CRS) rates during step-up dosing of talquetamab, a T-cell–engaging antibody approved for relapsed/refractory multiple myeloma (RRMM), in a real-world setting. While the MonumenTAL-1 trial reported a 77% CRS incidence, the impact of individual step-up doses had not been examined.

Fifty patients completing the step-up dosing schedule were analyzed. Overall, CRS occurred in 80% of patients, but rates differed across doses. The first and second step-up doses were associated with higher CRS rates (28% and 34%, respectively), whereas the fourth dose caused CRS in only 4% of patients, and this was limited to grade 1 severity. Time to CRS onset was similar across doses, and prior exposure to T-cell–redirecting therapy did not influence CRS occurrence.

These findings suggest that the fourth talquetamab step-up dose is highly tolerable and could be administered safely in outpatient settings. Reducing inpatient monitoring for later doses may decrease hospitalization time and lower healthcare costs, improving convenience and efficiency of RRMM treatment.
 

 

 

"Health system costs and autologous stem cell transplant receipt for participants with multiple myeloma in the Australian 45 and Up Study"

Source

Sarsha Yap, Anna Kelly, David Goldsbury, Marianne F. Weber, Xue Qin Yu, Qingwei Luo, Karen Canfell, Eleonora Feletto, Health system costs and autologous stem cell transplant receipt for participants with multiple myeloma in the Australian 45 and Up Study, Leukemia Research, 2025,108100, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2025.108100. September 16, 2025. 

Overview

This study examined healthcare costs and autologous stem cell transplant (ASCT) use among Australians diagnosed with multiple myeloma (MM) between 2006 and 2019, using data from the 45 and Up Study cohort. A total of 520 MM patients were identified and compared with matched participants without cancer to calculate excess health system costs from two years before diagnosis up to five years after.

The analysis showed that mean excess costs were $8,846 in the year before diagnosis and peaked at $66,249 in the year after diagnosis. From two to five years post-diagnosis, excess costs remained high, ranging from $36,453 to $43,059 per person. Within five years, 24% of patients received ASCT. Older age at diagnosis was linked to both lower healthcare costs and lower likelihood of receiving ASCT.

These findings highlight that MM places a substantial and sustained financial burden on the healthcare system. The data provide important insights for planning future healthcare resources and strategies to manage costs while optimizing patient care in MM.
 

 

 

"Is it Necessary to Achieve a Very Good Partial Response Prior to Transplant? Comparison of Outcomes in Pre-Transplant Partial Response Versus Very Good Partial Response or Deeper"

Source

Mirgh, S., Kapoor, J., Bhatia, N. et al. Is it Necessary to Achieve a Very Good Partial Response Prior to Transplant? Comparison of Outcomes in Pre-Transplant Partial Response Versus Very Good Partial Response or Deeper. Indian J Hematol Blood Transfus (2025). https://doi.org/10.1007/s12288-025-02140-6  September 16, 2025. 

Overview

This retrospective study evaluated 166 patients with multiple myeloma who underwent their first autologous stem cell transplantation (ASCT) between 2002 and 2018 to determine whether the depth of response before transplant affected outcomes. Patients were grouped by pre-transplant response: partial response (PR) versus very good partial response or better (≥VGPR). Most patients (63%) received bortezomib-based induction therapy, and the median follow-up was 46 months.

The study found that median progression-free survival (PFS) and overall survival (OS) were similar between patients in pre-transplant PR versus ≥VGPR (PFS: 40 vs. 47 months; OS: 71 vs. 83 months). Importantly, 86% of patients in PR achieved ≥VGPR by day +100 post-transplant. Achieving ≥VGPR after transplant, rather than before, was linked to improved survival.

These results suggest that delaying ASCT to achieve a deeper pre-transplant response or switching to salvage therapy may not be necessary, as most patients in PR deepen their response after transplant and derive similar long-term benefits.
 

 

 

"Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: A Comprehensive Exposure-Response Analysis of the DREAMM-8 Study"

Source

Hanafin, P., Ho, Y.L., Papathanasiou, T. et al. Belantamab Mafodotin with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: A Comprehensive Exposure-Response Analysis of the DREAMM-8 Study. Targ Oncol (2025). https://doi.org/10.1007/s11523-025-01174-0 September 16, 2025.  

Overview

This analysis from the phase 3 DREAMM-8 study evaluated how initial belantamab mafodotin exposure affects efficacy and safety in patients with relapsed/refractory multiple myeloma (RRMM) receiving belantamab with pomalidomide and dexamethasone (BPd). Patients in the BPd arm received 2.5 mg/kg intravenously in cycle 1, followed by 1.9 mg/kg every 4 weeks. Using pharmacokinetic data, researchers examined the relationship between cycle 1 belantamab exposure and treatment outcomes.

Higher cycle 1 exposure was linked to deeper responses, including higher rates of complete response and minimal residual disease negativity, without increasing grade ≥3 ocular adverse events. Simulations comparing an initial dose of 1.9 mg/kg versus 2.5 mg/kg suggested that the lower dose would reduce the likelihood of deep responses without improving ocular safety.

These findings indicate that starting belantamab mafodotin at 2.5 mg/kg in BPd therapy offers better treatment responses for RRMM patients while maintaining a similar safety profile.
 

 

 

"Immunoglobulin prophylaxis should be initiated after bispecific antibody therapy in multiple myeloma, regardless of IgG levels"

Source

Rahul Banerjee, Meera Mohan, Kai Rejeski, Benjamin R. Puliafito, Diana D. Cirstea, Gurbakhash Kaur, Shonali Midha, Georgia J. McCaughan, Nikhil M. Kumar, Nikita Mehra, Bhausaheb Bagal, Noopur S. Raje; Immunoglobulin prophylaxis should be initiated after bispecific antibody therapy in multiple myeloma, regardless of IgG levels. Blood Adv 2025; 9 (18): 4720–4726. doi: https://doi.org/10.1182/bloodadvances.2025016490  September 16, 2025  

Overview

This viewpoint examines the use of immunoglobulin replacement therapy (IgRT) to reduce infection risks in multiple myeloma (MM) patients receiving bispecific antibodies (bsAbs) such as teclistamab, elranatamab, linvoseltamab, and talquetamab. While bsAbs show strong anti-myeloma activity, they carry persistent infectious risks. IgRT, delivered intravenously or subcutaneously, can help mitigate these risks.

The authors compare two approaches: primary prophylaxis, where IgRT is started regardless of IgG levels, and preemptive treatment, where IgRT is only given once IgG falls below a threshold. They argue that primary prophylaxis is safer and simpler, offering consistent protection without relying on potentially misleading IgG measurements. The piece also explores strategies to improve cost-effectiveness of IgRT globally.

Overall, the authors conclude that denying IgRT based on arbitrary IgG thresholds is not scientifically justified, and primary IgRT prophylaxis should be considered for MM patients receiving bsAb therapy to minimize infection risks.
 

 

 

"Can baseline cytomegalovirus IgG titers predict cytomegalovirus reactivation after ide-cel therapy?"

Source

Taku Kikuchi, Ukyo Kondo, Shotaro Sugita, Miyu Watanabe, Chiaki Matsumoto, Moe Nomura-Yogo, Kodai Kunisada, Haruka Sawada, Kota Sato, Tomomi Takei, Mizuki Ogura, Yu Abe, Kenshi Suzuki, Osamu Hosoya, Tadao Ishida, Nobuhiro Tsukada; Can baseline cytomegalovirus IgG titers predict cytomegalovirus reactivation after ide-cel therapy?. Blood Adv 2025; 9 (18): 4716–4719. doi: https://doi.org/10.1182/bloodadvances.2025017174 September 16, 2025.  

Overview

This letter to the editor reports on a study evaluating the risk of cytomegalovirus (CMV) reactivation in multiple myeloma patients receiving idecabtagene vicleucel (ide-cel) CAR-T therapy. While CAR-T therapy is effective for relapsed/refractory disease, it carries risks including infections. The study analyzed 44 CMV-seropositive patients treated with ide-cel at the Japanese Red Cross Medical Center to determine whether baseline CMV IgG titers could predict reactivation.

Results showed a cumulative CMV reactivation incidence of 49.5% at 3 months and 57.2% at 6 months. Patients with higher baseline CMV IgG levels (≥115.6 AU/mL) had significantly higher reactivation rates than those with lower levels (<115.6 AU/mL). Prophylactic immunoglobulin administration reduced reactivation in the high IgG group, and clinically significant CMV reactivation occurred primarily in patients with high baseline titers.

The study suggests that measuring CMV IgG before ide-cel therapy can help identify patients at higher risk for reactivation, guiding monitoring strategies, prophylactic immunoglobulin use, and potentially antiviral prophylaxis. These findings may improve infection management and outcomes for CAR-T recipients, though larger studies are needed to validate the results.
 

 

 

"Circulating extracellular vesicle isomiR signatures predict therapy response in patients with multiple myeloma"

Source

Cristina Gómez-Martín, Esther E.E. Drees, Monique A.J. van Eijndhoven, Nils J. Groenewegen, Steven Wang, Sandra A.W.M. Verkuijlen, Jan R.T. van Weering, Ernesto Aparicio-Puerta, Leontien Bosch, Kris A. Frerichs, Christie P.M. Verkleij, Marie J. Kersten, Josée M. Zijlstra, Daphne de Jong, Catharina G.M. Groothuis-Oudshoorn, Michael Hackenberg, Johan R. de Rooij, Niels W.C.J. van de Donk, D. Michiel Pegtel, Circulating extracellular vesicle isomiR signatures predict therapy response in patients with multiple myeloma, Cell Reports Medicine, 2025, 102358, ISSN 2666-3791, https://doi.org/10.1016/j.xcrm.2025.102358. September 16, 2025. 

Overview

This study investigates a minimally invasive method to predict treatment response in multiple myeloma (MM), a cancer of plasma cells known for high genetic variability and inconsistent therapy outcomes. Researchers used IsoSeek, a high-resolution small RNA sequencing technique, to profile thousands of microRNAs (miRNAs) and their variants (isomiRs) from extracellular vesicles in patient plasma. Machine learning models built from these data accurately predicted response in relapsed/refractory MM patients treated with daratumumab-containing regimens, achieving an area under the curve of 0.98.

A specific classifier including the plasma cell–selective miR-148-3p predicted durable responses of six months or longer, as well as improved progression-free and overall survival. Target analysis connected the predictive miRNA signature to known MM drug targets, including BCL2 and MYC, supporting its biological relevance. This approach provides a noninvasive alternative to bone marrow biopsies, allowing clinicians to anticipate treatment outcomes and potentially personalize therapy decisions in MM.
 

 

 

"Fludarabine Lymphodepletion Exposure is Associated with Toxicities after Idecabtagene-vicleucel in Relapsed/Refractory Multiple Myeloma: Real-World Experience from the US Myeloma Immunotherapy Consortium"

Source

Sweiss, Karen et al. Fludarabine Lymphodepletion Exposure is Associated with Toxicities after Idecabtagene-vicleucel in Relapsed/Refractory Multiple Myeloma: Real-World Experience from the US Myeloma Immunotherapy Consortium. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 0, Issue 0  DOI: 10.1016/j.jtct.2025.08.015 September 17, 2025. 

Overview

This study evaluated how fludarabine (Flu) exposure affects outcomes and toxicities in patients with relapsed/refractory multiple myeloma (RRMM) receiving ide-cel, a BCMA-directed CAR-T therapy. Fludarabine, used in lymphodepletion before CAR-T infusion, shows significant variability in how it is processed in the body. Researchers retrospectively analyzed 285 patients across 10 US centers, using patient-specific factors like body weight and kidney function to predict Flu exposure (AUC) and peak concentration.

Higher predicted Flu exposure was linked to an increased risk of CAR-T–related toxicities, including cytokine release syndrome, neurotoxicity (ICANS), and low blood counts such as thrombocytopenia and neutropenia. There was also a trend toward higher infection risk. Flu exposure showed a potential association with overall response at day 90. These findings suggest that personalized monitoring and dosing of fludarabine could help reduce CAR-T–related toxicities, though prospective studies are needed to confirm this approach.
 

 

 

"Review the less explored correlation of VEGF signaling pathway with angiogenesis in multiple myeloma"

Source

Ramezani, F., Soumee, M.M., Kazempour, A. et al. Review the less explored correlation of VEGF signaling pathway with angiogenesis in multiple myeloma. Comp Clin Pathol (2025). https://doi.org/10.1007/s00580-025-03707-5 September 17, 2025. 

Overview

This review examines the role of angiogenesis in multiple myeloma (MM), with a particular focus on vascular endothelial growth factor (VEGF). Angiogenesis—the formation of new blood vessels—is critical for tumor growth and disease progression in MM. Malignant plasma cells in the bone marrow secrete VEGF and other angiogenic factors, which increase microvessel density (MVD) and correlate with disease activity. VEGF drives angiogenesis by binding to its receptors and activating signaling pathways, including the MAPK cascade, which stimulates endothelial cell proliferation. VEGF expression and MVD are therefore important biomarkers for monitoring MM progression. The review also highlights therapeutic strategies targeting VEGF signaling, such as monoclonal antibodies and small-molecule inhibitors, which have shown promising results in preclinical studies and may offer potential clinical benefits for patients with multiple myeloma.
 

 

 

"The Two Sides of Bispecific Antibodies in Multiple Myeloma: Where Trial Promise Meets Real-World Practice"

Source

Sonja Zweegman, Febe Smits, Niels W.C.J. van de Donk; The Two Sides of Bispecific Antibodies in Multiple Myeloma: Where Trial Promise Meets Real-World Practice. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-25-0292 September 17, 2025. 

Overview

This study highlights a gap between the efficacy of the bispecific antibody teclistamab observed in clinical trials and its real-world effectiveness in patients with multiple myeloma. Understanding the factors that drive this difference is essential to identify which patients are most likely to benefit from teclistamab, optimize treatment strategies for high-risk populations, and support more personalized care approaches. These insights can help improve patient outcomes while promoting sustainable and efficient use of bispecific antibody therapies in everyday clinical practice.
 

 

 

"Sarcopenia and fat loss from serial CT predict survival in multiple myeloma patients undergoing stem cell transplantation"

Source

Kylies, J., Brauneck, E., Priemel, M. et al. Sarcopenia and fat loss from serial CT predict survival in multiple myeloma patients undergoing stem cell transplantation. World J Surg Onc 23, 336 (2025). https://doi.org/10.1186/s12957-025-04007-6  September 17, 2025.  

Overview

This study examined changes in body composition over time in multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) and how these changes relate to survival and functional outcomes. Using sequential CT scans, researchers measured skeletal muscle and visceral fat, finding significant declines in both men and women over the disease course. Greater losses were observed in patients with high disease activity or those receiving ASCT. Reductions in skeletal muscle index (SMI) and visceral adipose tissue (VAT) independently predicted shorter survival and worse functional status. Patients losing ≥10% of SMI or ≥12% of VAT had notably shorter survival and more pronounced functional decline. These findings suggest that routine CT-based body composition assessments can help identify high-risk patients, guide early interventions, and improve risk stratification in multiple myeloma care.
 

 

 

"Association between type 2 diabetes and prevalence of monoclonal gammopathy of undetermined significance in a large screened U.S. population"

Source

Etienne X. Holder, Mallory Bernstein, Jia Wan, Esther A. Lam, Jane Emerson, Yatchana Kataria, Gary Zirpoli, Sabrina Racine-Brzostek, Christopher A. Haiman, Qiuyin Cai, Alexander Reiner, Julie R. Palmer, Pinkal Desai, Wendy Cozen, Kimberly A. Bertrand. Association between type 2 diabetes and prevalence of monoclonal gammopathy of undetermined significance in a large screened U.S. population [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B131.   

Overview

This study examined whether type 2 diabetes (T2D) is linked to the prevalence of monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, in a multi-racial population. Researchers analyzed data from three large cohorts, including 916 MGUS cases and 7,160 non-cases, and accounted for age, sex, race, BMI, and diabetes treatment. Contrary to expectations, having T2D—whether treated with metformin, other medications, or untreated—was not associated with a higher prevalence of MGUS. Results were consistent across BMI groups and cohorts. These findings suggest that T2D does not increase the risk of developing MGUS, highlighting the need for further research with additional cohorts, such as the Women’s Health Initiative, to confirm these results.
 

 

 

"Cardiovascular disease mortality among multiple myeloma patients treated with chemoimmunotherapy"

Source

Jacqueline B. Vo, Martha S. Linet, Keli’i Shontell, Wayne R. Lawrence, Kekoa Taparra, Jaimie Z. Shing, Paloma R. Mitra, Rochelle E. Curtis, Sara J. Schonfeld, Graça M. Dores, Lindsay M. Morton. Cardiovascular disease mortality among multiple myeloma patients treated with chemoimmunotherapy, 2000-2021 [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B126.     

Overview

This study examined cardiovascular disease (CVD) mortality among 53,910 multiple myeloma (MM) patients treated with chemotherapy or immunotherapy, focusing on racial and ethnic differences. Using SEER registry data from 2000–2020, researchers found that Black and Native Hawaiian/Pacific Islander (NHPI) patients faced significantly higher CVD mortality compared with White patients, while rates among Asian American, Hispanic, and American Indian/Alaska Native patients were not significantly elevated. The greatest disparities were observed in younger Black patients (aged 20–49) and NHPI patients aged 50–64, as well as those living in non-metropolitan or lower-income areas. By 10 years post-diagnosis, absolute CVD mortality was highest among AI/AN, Black, and NHPI patients. These findings highlight pronounced racial and ethnic disparities in CVD mortality among MM survivors and underscore the need for targeted interventions, improved clinician awareness, and strategies to reduce modifiable CVD risks in high-risk populations.
 

 

 

"Selinexor-based treatments are associated with increased expression of T cell activation markers in multiple myeloma. Blood Immunology & Cellular Therapy 2025"

Source

Jacqueline B. Vo, Martha S. Linet, Keli’i Shontell, Wayne R. Lawrence, Kekoa Taparra, Jaimie Z. Shing, Paloma R. Mitra, Rochelle E. Curtis, Sara J. Schonfeld, Graça Yubin Kang, Jadee L Neff, Andrea Ellero, William R Jeck, Cristina Gasparetto, Xiaobei Wang, Xufeng Chen, Zuowei Su, Christopher J. Walker; Selinexor-based treatments are associated with increased expression of T cell activation markers in multiple myeloma. Blood Immunology & Cellular Therapy 2025; 100009. doi: https://doi.org/10.1016/j.bict.2025.100009  September 18, 2025.      

Overview

This study explored how selinexor (SEL), an exportin 1 inhibitor, affects the bone marrow microenvironment and myeloma cells in patients with multiple myeloma (MM) treated on the STOMP trial. Using digital spatial profiling of CD138+ myeloma cells and CD3+ T cells, researchers identified that higher baseline expression of proliferation markers in myeloma cells, including p-MEK1 and p-AKT1, was linked to poorer progression-free survival and may serve as predictive biomarkers of response. In T cells collected during treatment response, SEL induced activation markers such as EGFR, CD127, granzyme B, and pERK1/2, without upregulating inhibitory immune checkpoints like LAG3, PD-1, or CTLA4, suggesting T cell exhaustion is not a driver of resistance. These findings indicate that SEL exerts anti-myeloma activity while preserving T cell function, supporting its potential use in combination with CAR T-cell therapies or bispecific antibodies for MM.
 

 

 

 

"Poor Outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study"

Source

Sarah Cayla, Lionel Karlin, Jerome Lambert, Anne Lazareth, Alexis Talbot, Mohamad Mohty, Florent Malard, Marie-Odile Petillon, Salomon Manier, Ibrahim Yakoub-Agha, Denis Caillot, Ingrid Lafon, Xavier Leleu, Niels Moya, Bruno Royer, Jean Marc Schiano de Colella, Gabriel Brisou, Cyrille Touzeau, Aurore Perrot, Pierre Bories, Laure Vincent, Hanane Guedon, Olivier Decaux, Benoît Ferment, Roch Houot, Steven Le Gouill, Noemie Bigot, Thierry Facon, Jill Corre, Hervé Avet-Loiseau, Philippe Moreau, Bertrand Arnulf; Poor Outcomes with BCMA-targeting bispecific antibodies following early relapse from ide-cel: a real-world French study. Blood Adv 2025; bloodadvances.2025017597. doi: https://doi.org/10.1182/bloodadvances.2025017597  September 18, 2025.      

Overview

This real-world study evaluated outcomes for 154 patients with relapsed/refractory multiple myeloma who progressed after idecabtagene vicleucel (ide-cel) therapy, with a median time to progression of six months. Salvage treatments included anti-BCMA bispecific antibodies (BsAbs), non-BCMA BsAbs targeting GPRC5D or FcRH5, combinations of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies, among others. Overall, median overall survival was 12.1 months, and median progression-free survival was 3.5 months. Patients receiving BsAbs had higher response rates (36%) compared with other therapies (13%), while non-BCMA BsAbs showed the strongest efficacy, with a 67% response rate, longer survival, and extended progression-free intervals. Poor outcomes were linked to early relapse (≤6 months), extramedullary disease, and having received more than three prior therapy lines. These findings suggest that while anti-BCMA BsAbs have limited benefit post-ide-cel, non-BCMA BsAbs may offer a promising strategy, highlighting the importance of diversifying therapeutic targets after early ide-cel relapse.
 

 

 

"Prevalence, detection, and clinical implications of BRAF V600E and NRAS Q61R mutations in multiple myeloma BM-FFPE tissues using digital droplet PCR"

Source

Sharma, N.S., Nataraj, K.S. & Choudhary, B. Prevalence, detection, and clinical implications of BRAF V600E and NRAS Q61R mutations in multiple myeloma BM-FFPE tissues using digital droplet PCR. Med Oncol 42, 478 (2025). https://doi.org/10.1007/s12032-025-03032-5 September 18, 2025.       

Overview

This study explored the use of droplet digital PCR (DD-PCR) to detect BRAF V600E and NRAS Q61R mutations in bone marrow samples from Indian patients with multiple myeloma (MM). Mutations were found in over 80% of samples, with BRAF V600E levels varying by disease stage—lowest in intermediate MM and significantly higher in advanced MM—and declining after treatment. NRAS Q61R was more common in progressive disease and tended to increase with advancing stage. Higher mutation burdens for both BRAF and NRAS were linked to reduced two-year progression-free survival. The study demonstrates that DD-PCR on formalin-fixed, paraffin-embedded bone marrow tissue is feasible and provides valuable molecular insights, although limitations include potential sampling biases, DNA quality, and a small single-center cohort. These findings suggest that DD-PCR could complement sequencing and aid clinical stratification in MM if validated in larger populations.
 

 

 

"CD24 expression for better outcome prediction in newly diagnosed multiple myeloma patients"

Source

Wang, Lu MDa; Geng, Hui MDa; Ma, Jie MDa; Li, Youliang MDb; Yin, Qichao MDa; Jiang, Yan MDc,*. CD24 expression for better outcome prediction in newly diagnosed multiple myeloma patients. Medicine 104(38):p e44298, September 19, 2025. | DOI: 10.1097/MD.0000000000044298     

Overview

This study examined whether CD24 expression levels could help predict outcomes in newly diagnosed multiple myeloma. Researchers analyzed bone marrow samples from 54 patients and divided them into high- and low-expression groups using a median threshold. Patients with higher CD24 expression had significantly longer overall survival (50 months vs. 24 months) compared with those with lower expression. Even after adjusting for disease stage and cytogenetic risk, high CD24 remained an independent predictor of better outcomes. The findings suggest that CD24 may influence disease behavior by affecting plasma cell adhesion and drug resistance, making it a promising biomarker for more precise prognostic assessment in multiple myeloma.
 

 

 

"The endogenous T cell landscape is reshaped by CAR-T cell therapy and predicts treatment response in multiple myeloma"

Source

Frede, J., Poller, J.C., Shi, K. et al. The endogenous T cell landscape is reshaped by CAR-T cell therapy and predicts treatment response in multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02766-5 September 19, 2025. 

Overview

CAR-T cell therapy can work well at first for people with multiple myeloma, but the benefits usually don’t last, and later rounds of immunotherapy often don’t work as well. This study looked closely at how CAR-T cells interact with the immune system in patients receiving anti-BCMA CAR-T treatment. The researchers found that CAR-T therapy causes major shifts in a patient’s own T cells. In particular, they discovered a new type of CD8+ T cell linked to poor treatment results. This group of cells shows up as the body’s natural T cells are depleted and reshaped, weakening the immune system’s ability to fight the cancer. The study also suggests that blocking the TIM3/GAL9 pathway could help T cells avoid exhaustion and survive longer, which might improve future treatments. Overall, the research offers a way to measure and adjust the “mileage” of the immune system so that repeated therapies don’t lose effectiveness, even when targeting different cancer markers.
 

 

 

"Optical Genome Mapping (OGM): Validation and Clinical Utility in the Cytogenetic Diagnosis of Multiple Myeloma"

Source

A. Cisneros, M. Mallo, A. Méndez-López, et al., “Optical Genome Mapping (OGM): Validation and Clinical Utility in the Cytogenetic Diagnosis of Multiple Myeloma,” American Journal of Hematology (2025): 1–4, https://doi.org/10.1002/ajh.70077. September 20, 2025. 

Overview

Multiple myeloma is known for its genetic complexity, and identifying chromosomal abnormalities is key for predicting outcomes and guiding treatment. Traditional tools like karyotyping and FISH have been essential, but they often miss important alterations. This study explored how optical genome mapping (OGM) compares with FISH in detecting these changes. The researchers analyzed samples from 90 patients, ultimately focusing on 66. They found that OGM could detect all abnormalities that FISH picked up, plus many more, including additional aneuploidies, translocations, and catastrophic events like chromoplexy and chromothripsis. In fact, OGM reclassified the genetic risk profile in two-thirds of cases, far higher than previously reported.

The study also showed that OGM works best when analyzing purified plasma cells rather than whole bone marrow, where results can be less reliable if infiltration is low. Still, OGM provided a broader and more detailed picture of the genome, revealing complex karyotypes and events that standard tests cannot capture. These insights could refine risk scoring systems and improve how patients are stratified for treatment. While FISH remains the gold standard for some targeted alterations, the authors argue that OGM should be used routinely at diagnosis, with FISH as a complementary test when plasma cell infiltration is low. Because OGM can uncover hidden genetic drivers and refine prognosis, they conclude that multiple myeloma may be one of the cancers to benefit most from adopting this technology.
 

 

 

"Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study"

Source

Ajai Chari, Niels W.C.J. van de Donk, Bhagirathbhai Dholaria, Katja C Weisel, Maria-Victoria Mateos, Hartmut Goldschmidt, Tom G Martin, Daniel Morillo, Donna Reece, Paula Rodriguez-Otero, Manisha Bhutani, Anita D'Souza, Albert Oriol, Laura Rosiñol, Nizar J. Bahlis, Deeksha Vishwamitra, Sheri Skerget, Raluca I. Verona, Kalpana K Bakshi, Lijuan Kang, Thomas J Prior, Lien Vandenberk, Jaszianne Tolbert, Sangmin Lee, Damiette Smit, Ralph Wäsch; Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood 2025; blood.2025029360. doi: https://doi.org/10.1182/blood.2025029360  September 22, 2025.  

Overview

Talvey® (talquetamab), a bispecific antibody that targets GPRC5D, may work even better when combined with daratumumab for patients with relapsed or refractory multiple myeloma. In the phase 1b TRIMM-2 trial, 65 patients who had received a median of five prior treatments were given this combination. More than 60% were triple-class refractory, and about a quarter had already been treated with another bispecific antibody. Patients received talquetamab either once a week or every two weeks, along with daratumumab.

The most common side effects included mouth and skin issues, cytokine release syndrome, and infections. Severe side effects occurred in about 82% of patients, with two cases of dose-limiting toxicity in the every-two-weeks group. Despite this, the treatment was effective: response rates were 71% in the weekly group and 82% in the every-two-weeks group. Median progression-free survival was about 23 months for weekly dosing and 21 months for every-two-weeks dosing. Lab results suggest daratumumab helps by lowering immune-suppressing cells, making talquetamab more effective. Overall, the combination showed strong and lasting responses in heavily pretreated patients, with side effects similar to those expected from each drug alone.
 

 

 

"Target antigen and plasma cell phenotype are critical factors for sensitivity to response-adapted daratumumab therapy"

Source

Mark B Meads, Xiaohong Zhao, David R Noyes, Praneeth Sudalagunta, Alexandra Achille, Chaomei Zhang, Rafael Renatino Canevarolo, Maria Silva, Dario Magaletti, Danny DeAvila, Sonila Toska, Ashley Oates, Daniel Lastorino, Dietrich Werner Idiaquez, Jinming Song, Samer Sansil, Sean J Yoder, Ariel F Grajales-Cruz, Brandon J Blue, Ciara L Freeman, Jongphil Kim, Melissa Alsina, Jason Brayer, Ariosto Siqueira Silva, Xiaofei Song, Kenneth H Shain, Rachid C Baz; Target antigen and plasma cell phenotype are critical factors for sensitivity to response-adapted daratumumab therapy. Blood 2025; blood.2025029921. doi: https://doi.org/10.1182/blood.2025029921 September 22, 2025.   

Overview

This study tested a response-adapted approach using daratumumab alone in older patients newly diagnosed with multiple myeloma. Patients who showed at least a partial response after two cycles stayed on daratumumab, while those who did not had lenalidomide or bortezomib added. The overall response rate was 97%, and more than a third of patients were able to continue on daratumumab alone with few side effects.

Patients who responded well to daratumumab monotherapy had higher CD38 expression, distinct plasma cell gene programs, and an active immune microenvironment. Those who needed additional therapy showed stronger activity in adhesion, TNF, and KRAS signaling pathways, as well as more immune suppression. Tracking tumor evolution showed that resistance could emerge quickly, with certain subclones gaining resistance features even after just two cycles. At relapse, resistant cells had reduced CD38 expression and maintained resistance programs, suggesting that acquired resistance comes from reshaping transcriptional programs already present at diagnosis. This is the first trial to show that response-adapted daratumumab treatment is effective and to identify biomarkers linked to single-agent sensitivity in newly diagnosed, therapy-naïve older patients.
 

 

 

"Is there a universal standard of care for frontline therapy in multiple myeloma?"

Source

Lonial S. Is there a universal standard of care for frontline therapy in multiple myeloma? Clin Adv Hematol Oncol. 2025 Sep;23(6):379-381. PMID: 40982085.   

Overview

For most fit patients with newly diagnosed multiple myeloma in the United States, the standard frontline treatment is Dara-VRd—a four-drug combination of daratumumab, lenalidomide, bortezomib, and dexamethasone. This regimen is supported by the PERSEUS trial, which showed significantly improved survival compared with triplet therapy alone. In some cases, daratumumab may be swapped for isatuximab (Isa-VRd), or bortezomib may be replaced with carfilzomib (Dara-KRd or Isa-KRd). These regimens have also shown strong outcomes in clinical trials, with high rates of MRD negativity and deep responses.

The main side effects linked to CD38 antibodies like daratumumab or isatuximab are infections, which can be managed with antibiotics or intravenous immunoglobulin if needed. Adding these antibodies to backbone regimens does not generally increase toxicity beyond what is seen with VRd or KRd. At Emory, Dara-VRd is the go-to regimen for fit patients, while frail patients may benefit more from a three-drug option such as Dara-Rd, without bortezomib.

Dr. Lonial emphasized that the division between transplant-eligible and ineligible patients is not always clear, since many older patients in the U.S. still undergo transplant if they are fit. Rather than using age as a cutoff, he prefers to classify patients as fit or frail, tailoring treatment intensity accordingly. He also noted that variation in practice often reflects real differences in patient fitness and access to care. Still, access remains a major issue—particularly for Black patients, who are less likely to receive intensive induction or transplant.

Looking ahead, he expects more standardization around four-drug regimens, with newer therapies like CAR-T cells, bispecific antibodies, and antibody-drug conjugates moving into earlier treatment lines. He cautioned that clinical trial populations tend to be healthier than real-world patients, which means oncologists need to adapt regimens carefully in practice. His advice to community oncologists is to stay connected with major myeloma centers, since treatment standards are changing every few months, often faster than guidelines can keep up. By partnering with specialty centers, community providers can offer cutting-edge care close to home while also receiving guidance on dose adjustments and supportive care that comes from treating large volumes of patients.
 

 

 

"Immune MRD Status Informs Tumor MRD Outcome Prognostication in Patients with Multiple Myeloma on Lenalidomide"

Source

Ross S. Firestone, Anish K. Simhal, Devin McAvoy, Eric M. Jurgens, Juan-Jose Garcés, David Nemirovsky, Andriy Derkach, Kylee H. Maclachlan, Malin Hultcrantz, Sham Mailankody, Urvi A. Shah, Carlyn R. Tan, Neha Korde, Hani Hassoun, Sridevi Rajeeve, Hamza Hashmi, Heather J. Landau, Michael Scordo, Gunjan L. Shah, Sergio A. Giralt, Benjamin T. Diamond, Francesco Maura, Kinga Hosszu, David J. Chung, Ola Landgren, Saad Z. Usmani, Alexander M. Lesokhin; Immune MRD Status Informs Tumor MRD Outcome Prognostication in Patients with Multiple Myeloma on Lenalidomide   

Overview

Revlimid® (lenalidomide) maintenance is a common long-term strategy for patients with multiple myeloma after initial therapy or transplant, and being MRD-negative during treatment is usually a good sign. But the role of repeated MRD testing is less clear, especially when MRD comes back after a period of negativity. This phase II study followed patients for five years on continuous lenalidomide maintenance, also using advanced T cell profiling to better understand relapse risk.

The results showed that patients who lost MRD negativity had worse progression-free survival compared with those who stayed negative. Still, only about one-third of patients with MRD resurgence relapsed within two years, while the rest remained progression-free at last follow-up. Immune profiling revealed a potential explanation: patients with activated cytotoxic T cell signatures were more likely to relapse early, while those with quiescent, naïve T cell–dominated profiles tended to have durable remissions.

These findings suggest that combining MRD testing with immune profiling may better predict outcomes than MRD status alone. An “immune MRD” signature could help distinguish between patients at true risk of relapse and those who remain stable despite MRD positivity, pointing toward a more refined way to guide maintenance therapy.
 

 

 

"Real-World Treatment Patterns and Clinical Outcomes Among Patients With Triple-Class–Exposed and BCMA-Exposed Multiple Myeloma Within the United States"

Source

H. S. Mian, J. S. Harper, H. H. Le, et al. “Real-World Treatment Patterns and Clinical Outcomes Among Patients With Triple-Class–Exposed and BCMA-Exposed Multiple Myeloma Within the United States.” eJHaem 6, no. 5 (2025): e70145. https://doi.org/10.1002/jha2.70145  September 23, 2025.   

Overview

For patients with multiple myeloma who have already been treated with drugs from all three main classes and then exposed to BCMA-targeted therapy, treatment options are limited and outcomes are poor. This real-world study looked at 656 such patients in the U.S., with an average age of 66 and nearly six prior lines of therapy. Most had previously received daratumumab, pomalidomide, carfilzomib, and belantamab mafodotin.

After BCMA therapy, patients went on to 137 different treatment regimens, showing there is no clear standard of care. The most common next treatment was teclistamab, though many patients were retreated with drugs they had already received, such as carfilzomib, pomalidomide, or bortezomib. Outcomes were poor: the median time to either starting another treatment or death was just under seven months, and the time to stopping treatment or death was only three and a half months.

These findings show that heavily pretreated, BCMA-exposed patients face short remissions and limited options, underscoring the urgent need for new and more effective therapies.
 

 

 

"The impact of reduced dosing frequency of elranatamab on patient-reported outcomes in patients with relapsed or refractory multiple myeloma: Results from MagnetisMM-3"

Source

Bahlis, N.J., Nooka, A.K., DiBonaventura, M., Sullivan, S.T., Chaudhary, M.A., Aydin, D. and Mohty, M. (2025), The impact of reduced dosing frequency of elranatamab on patient-reported outcomes in patients with relapsed or refractory multiple myeloma: Results from MagnetisMM-3. HemaSphere, 9: e70224. https://doi.org/10.1002/hem3.70224  September 23, 2025.    

Overview

Elrexfio™ (elranatamab), a BCMA-targeting bispecific antibody, has shown strong activity in patients with relapsed or refractory multiple myeloma. In the Phase 2 MagnetisMM-3 trial, researchers looked at whether switching patients from weekly to every two-week dosing would affect quality of life. Patients who had already responded to therapy for at least six cycles were eligible to make the change.

Among both BCMA-naive and BCMA-exposed patients, most were able to switch schedules. Patient-reported outcomes were tracked for up to 18 months. Overall, quality of life—including measures of fatigue, pain, disease symptoms, and side effects—remained stable after the dosing switch. Some small changes were seen at later time points, but these were based on very few patients and were not considered meaningful. Importantly, patients did not report worsening symptoms after moving to less frequent dosing.

The results suggest that extending the dosing interval can ease the treatment burden without reducing effectiveness or safety. Patients had fewer clinic visits while maintaining disease control and stable quality of life. This supports every-two-week dosing as a practical and patient-friendly option for elranatamab, regardless of prior BCMA therapy.
 

 

 

"Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma"

Source

Garces, J.-J., Diamond, B., Sevcikova, T., Nenarokov, S., Bilek, D., Radova, E., Venglar, O., Kapustova, V., Firestone, R., Maclachlan, K., Simhal, A., Broskevicova, L., Vrana, J., Muronova, L., Popkova, T., Mihalyova, J., Plonkova, H., Durante, M., Ziccheddu, B., Simicek, M., Cho, H.J., Mulligan, G., Keats, J., Zihala, D., Landgren, O., Hajek, R., Usmani, S., Maura, F. and Jelinek, T. (2025), Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma. HemaSphere, 9: e70218. https://doi.org/10.1002/hem3.70218 September 23, 2025.    

Overview

In newly diagnosed multiple myeloma, circulating tumor cells (CTCs) are an important predictor of outcomes, but it has been unclear whether they simply reflect tumor burden or represent a unique biological feature. This study analyzed more than 500 patients from the CoMMpass dataset, with genomic and transcriptomic data available for most, and validated findings in another group of 135 patients.

High CTC levels were linked to aggressive disease features, including advanced stage, chromothripsis, APOBEC mutagenesis, and loss of tumor suppressor genes. Transcriptomic analysis showed that patients with elevated CTCs had more activity in genes tied to cell growth and proliferation, but weaker connections to immune response. CTCs also served as a practical stand-in for proliferation-related transcriptomic signatures, and in fact, provided even stronger prognostic information.

These results show that CTCs are not just a marker of tumor size but reflect underlying high-risk biology. Measuring CTCs could streamline risk assessment, offering a simpler yet more powerful way to guide clinical decisions for newly diagnosed myeloma patients.

 

 

"Ixazomib treatment has a dual effect on bone remodeling in patients with multiple myeloma: follow-up results from a phase 2 clinical study"

Source

Mette Bøegh Levring, Marta Diaz-delCastillo, Michael Tveden Gundesen, Oriane Cédile, Christian Walther Andersen, Anne Lerberg Nielsen, Hanne Elisabeth Højsgaard Møller, Pernille Just Vinholt, Jon Thor Asmussen, Ida Bruun Kristensen, Charlotte Guldborg Nyvold, Moustapha Kassem, Niels Abildgaard, Thomas Levin Andersen, Thomas Lund, Ixazomib treatment has a dual effect on bone remodeling in patients with multiple myeloma: follow-up results from a phase 2 clinical study, Bone, 2025, 117660, ISSN 8756-3282, https://doi.org/10.1016/j.bone.2025.117660. September 23, 2025.     

Overview

Myeloma bone disease is a serious complication of multiple myeloma that weakens bones, raises the risk of fractures, and lowers quality of life. Proteasome inhibitors, a common treatment for myeloma, have been shown to not only fight cancer cells but also strengthen bone. However, their side effects make long-term use difficult, especially for patients in remission. Ixazomib, an oral proteasome inhibitor, has a milder side effect profile and may be a safer option for extended use.

In a clinical study of 30 patients in remission, researchers looked at the impact of ixazomib on bone health. Earlier findings showed that short-term treatment increased bone volume and strengthened bone structures without affecting the activity of bone-forming cells. The new results, based on two years of treatment, found that ixazomib helps maintain those early gains by slowing down both bone breakdown and new bone formation. Over time, the bone became better mineralized, suggesting stronger, more stable bone.

These findings suggest that long-term use of ixazomib may help preserve bone health and prevent the progression of myeloma bone disease in patients who are in remission.
 

 

 

"Estimation of benefit to bispecific antibodies in US patients with lymphoma and multiple myeloma"

Source

Fausto Alfredo Rios-Olais, Talal Hilal; Estimation of benefit to bispecific antibodies in US patients with lymphoma and multiple myeloma. Blood Adv 2025; 9 (18): 4673–4675. doi: https://doi.org/10.1182/bloodadvances.2025016176 September 23, 2025.    

Overview

Myeloma bone disease is a serious complication of multiple myeloma that weakens bones, raises the risk of fractures, and lowers quality of life. Proteasome inhibitors, a common treatment for myeloma, have been shown to not only fight cancer cells but also strengthen bone. However, their side effects make long-term use difficult, especially for patients in remission. Ixazomib, an oral proteasome inhibitor, has a milder side effect profile and may be a safer option for extended use.

In a clinical study of 30 patients in remission, researchers looked at the impact of ixazomib on bone health. Earlier findings showed that short-term treatment increased bone volume and strengthened bone structures without affecting the activity of bone-forming cells. The new results, based on two years of treatment, found that ixazomib helps maintain those early gains by slowing down both bone breakdown and new bone formation. Over time, the bone became better mineralized, suggesting stronger, more stable bone.

These findings suggest that long-term use of ixazomib may help preserve bone health and prevent the progression of myeloma bone disease in patients who are in remission.
 

 

 

"High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing"

Source

Anaïs Schavgoulidze, Aurore Perrot, Xavier Leleu, Titouan Cazaubiel, Marie-Lorraine Chretien, Pierre Feugier, Karim Belhadj, Salomon Manier, Murielle Roussel, Sabine Brechignac, Frederique Orsini Piocelle, Mohamad Mohty, Jean Marc Schiano de Colella, Margaret Macro, Didier Adiko, Mamoun Dib, Jean Fontan, Carine Motard, Didier Bouscary, Laurent Pascal, Virginie Roland, Francois Lifermann, Jana Armelle Bakala, Lydia Montes, Celine Kennel, Philippe Rey, Valentine Richez, Faiza Keddar, Laurent Frenzel, Claire Calmettes, Carine Chaleteix, Isabelle Plantier, Emilie Chalayer, Anna Schmitt, Christophe Roul, Hélène Demarquette, Chloe Cerutti, Luka Pavageau, Laure Derrier, Hervé Avet-Loiseau, Jill Corre; High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing. Blood 2025; blood.2025029999. doi: https://doi.org/10.1182/blood.2025029999  September 24, 2025. 

Overview

Researchers know that not all cases of multiple myeloma behave the same way, and much of this difference comes from the genetic features of the cancer cells. To create a unified way of identifying patients with more aggressive disease, the International Myeloma Society and the International Myeloma Working Group recently developed a high-risk genomic model. In this large study, genetic testing was performed on more than 6,500 patients newly diagnosed with myeloma and over 1,500 patients at first relapse. Results showed that about 22% of newly diagnosed patients and nearly 37% of relapsed patients were considered high-risk using this genomic model.

When looking at patient outcomes, those classified as high-risk at diagnosis had a median progression-free survival of 30 months, compared with 51 months for standard-risk patients. Importantly, traditional cytogenetic risk criteria did not clearly separate patients into high- and standard-risk groups the way the new genomic model did. Certain specific genetic changes, including del(17p), TP53 mutations, and some chromosome 1 changes, were linked to worse outcomes. Patients with multiple high-risk genetic features had an even poorer prognosis.

Overall, this study confirms that the new genomic definition of high-risk myeloma is effective at identifying patients who face a greater chance of early relapse, helping doctors better understand and classify risk in newly diagnosed cases.
 

 

 

"Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial"

Source

Françoise Kraeber-Bodere, Bastien Jamet, Sonja Zweegman, Aurore Perrot, Cyrille Hulin, Denis Caillot, Thierry Facon, Xavier Leleu, Karim Belhadj, Emmanuel Itti, Lionel Karlin, Clement Bailly, Mark-David Levin, Monique C. Minnema, Caroline Bodet-Milin, Bart de Keizer, Jill Corre, Pieter Sonneveld, Philippe Moreau, Thomas Carlier, Cyrille Touzeau; Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial. Blood 2025; blood.2025030084. doi: https://doi.org/10.1182/blood.2025030084 September 24, 2025. 

Overview

The CASSIOPEIA trial showed that adding daratumumab to standard induction and consolidation treatment, and continuing with daratumumab maintenance, improves progression-free survival for newly diagnosed myeloma patients who are eligible for transplant. A related study, called CASSIOPET, looked at whether PET/CT scans done before maintenance treatment could help predict outcomes, especially when combined with minimal residual disease (MRD) testing in the bone marrow.

In this study, 225 patients had PET/CT results available. Among those who had positive PET scans at the start, 92% became PET-negative before maintenance. Patients who reached PET-negativity tended to live longer without disease progression, and there was also a strong trend toward longer overall survival. Importantly, patients who were both PET-negative and MRD-negative had the best outcomes, with significantly longer progression-free survival than those who remained positive on either test.

For patients treated with daratumumab, becoming PET-negative was linked to longer survival, and achieving both PET and MRD negativity was an especially powerful predictor of benefit. These findings confirm that PET/CT scans, when used alongside bone marrow MRD testing, can provide valuable information about prognosis in newly diagnosed patients receiving daratumumab-based treatment.
 

 

 

"In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma"

Source

Knudsen, N.H., Escobar, G., Korell, F. et al. In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma. Nature (2025). https://doi.org/10.1038/s41586-025-09489-8  September 24, 2025. 

Overview

CAR T-cell therapy has shown powerful results in blood cancers, including multiple myeloma, but many patients eventually relapse as the modified T cells lose strength over time. To better understand what controls CAR T-cell persistence, researchers used CRISPR gene-editing screens in a myeloma model. They tracked how different genetic changes affected CAR T-cell growth and survival both in the lab and inside tumors at various time points.

The study revealed that some genes have context-specific effects. For example, removing RASA2 or SOCS1 boosted T-cell expansion in the lab, while loss of PTPN2, ZC3H12A, or RC3H1 gave CAR T cells an early advantage inside the body. Most importantly, the researchers found that the gene CDKN1B, which regulates the cell cycle, was a key factor limiting CAR T-cell persistence at later stages. When CDKN1B was removed, the CAR T cells expanded more, functioned better, cleared tumors more effectively, and significantly prolonged survival.

These findings highlight CDKN1B as a promising target to improve CAR T-cell therapy for multiple myeloma and show the value of in vivo CRISPR screening for discovering new ways to make these treatments more durable and effective.
 

 

 

"Prognostic value of tumor dissemination feature based on baseline 18F-FDG PET/CT in patients with newly diagnosed multiple myeloma"

Source

Guo, Yue-Honga,*; Tian, Yingb,*; Huang, Jing-Weia; Liu, Ai-Junb; Yang, Min-Fua. Prognostic value of tumor dissemination feature based on baseline 18F-FDG PET/CT in patients with newly diagnosed multiple myeloma. Nuclear Medicine Communications ():10.1097/MNM.0000000000002059, September 25, 2025. | DOI: 10.1097/MNM.0000000000002059 September 25, 2025. 

Overview

This study looked at whether a new PET/CT measurement, called Dmax, could help predict outcomes in patients newly diagnosed with multiple myeloma. Dmax measures the largest distance between two cancer lesions in the body, giving an idea of how far the disease has spread. Researchers compared Dmax to other PET/CT markers and clinical factors to see which best predicted event-free survival.

The study included 58 patients who were followed for a median of 42 months. Several factors, including high calcium, high creatinine, large metabolic tumor volume, and advanced disease stage, were linked to worse outcomes in initial analyses. However, when all factors were considered together, only Dmax greater than 0.44 meters remained a significant independent predictor of event-free survival.

These findings suggest that Dmax may be a useful new way to assess prognosis in newly diagnosed myeloma patients, though larger studies are needed to confirm its role.
 

 

 

"Somatic variants and frequencies of familial myeloma germline predisposition genes among patients within the CoMMpass dataset"

Source

Akkus, E., Tuncalı, T., Akin, H. Y., & Beksaç, M. (2025). Somatic variants and frequencies of familial myeloma germline predisposition genes among patients within the CoMMpass dataset. Expert Review of Hematology. https://doi.org/10.1080/17474086.2025.2567299  September 25, 2025. 

Overview

Researchers have long studied inherited genetic factors linked to familial multiple myeloma, but less is known about how these same genes may be altered in a non-inherited, or somatic, way. This study analyzed data from the CoMMpass study to look at somatic variants in 179 genes previously tied to familial myeloma. The cohort included patients both with and without a family history of blood cancers.

The analysis found 1,863 somatic variants in these genes, most of which were substitutions, with missense variants being the most common type. Several genes with potential roles in disease development stood out, including DIS3, LRP1B, EP300, SAMHD1, ARID1A, and others. Importantly, these pathogenic variants did not differ by age, family history, or other demographic factors, suggesting they occur broadly across patient groups.

The findings point to a high rate of potentially disease-related somatic changes in genes already known to predispose families to myeloma. This highlights new candidate genes for further study and suggests they may play an important role in how myeloma develops.

 

 

"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; 146 (13): 1550–1560. doi: https://doi.org/10.1182/blood.2025028403  September 25, 2025. 

Overview

The development of multiple myeloma is closely tied to genetic changes, but these do not fully explain why patients respond so differently to treatment. New research shows that epigenetic changes—alterations that affect how genes are expressed without changing the DNA sequence—play a major role in both the onset of myeloma and resistance to therapy. These changes disrupt normal cell processes such as DNA repair, stress response, and cell survival, allowing myeloma cells to adapt and evolve under treatment pressure.

One key area of focus is histone acetylation, a common form of histone modification that helps regulate how DNA is packaged and which genes are turned on or off. Abnormal patterns of histone acetylation, combined with changes in chromatin remodeling, create instability in gene activity and drive disease progression. This has led to strong interest in drugs that target epigenetic mechanisms, including inhibitors of histone deacetylases, CREB-binding protein/p300, and bromodomain and extraterminal proteins.

While these therapies show promise, challenges remain, such as limited effectiveness in some patients and the potential for resistance. Ongoing research is working to better understand how these drugs interact with the complex epigenetic landscape of myeloma, with the goal of developing more precise and durable treatment strategies.
 

 

 

"Biallelic antigen escape is a mechanism of resistance to anti-CD38 antibodies in multiple myeloma"

Source

Benjamin Diamond, Linda Baughn, Mansour Poorebrahim, Alexandra M. Poos, Holly Lee, Marcella Kaddoura, J. Erin Wiedmeier-Nutor, Michael Durante, Gregory Otteson, Dragan Jevremovic, Hongwei Tang, Stefan Fröhling, Marc A. Baertsch, Marios Papadimitriou, Bachisio Ziccheddu, Tomas Jelinek, Cendrine Lemoine, Alexey Rak, Damian J. Green, Ola Landgren, Paola Neri, Leif Bergsagel, Esteban Braggio, Shaji Kumar, Marc S. Raab, Rafael Fonseca, Nizar Bahlis, Niels Weinhold, Francesco Maura; Biallelic antigen escape is a mechanism of resistance to anti-CD38 antibodies in multiple myeloma. Blood 2025; 146 (13): 1575–1585. doi: https://doi.org/10.1182/blood.2024028107  September 25, 2025. 

Overview

Monoclonal antibodies that target CD38, such as daratumumab and isatuximab, are an important part of multiple myeloma treatment. While they have improved patient outcomes, relapse remains common, and the ways myeloma cells resist these therapies are not fully understood. One concern is whether tumor cells can develop lasting resistance by losing or mutating the CD38 gene itself.

To explore this, researchers analyzed genomic data from more than 800 patients, including those newly diagnosed, those relapsed but not yet treated with CD38 antibodies, and those relapsed after receiving CD38 therapy. They found that 20% of patients who relapsed after treatment had lost CD38 expression, and in some cases, both copies of the gene were disrupted. In two patients, different subclones independently developed similar CD38 mutations, showing convergent evolution. Laboratory studies revealed that certain mutations weakened antibody binding and reduced immune activity. Interestingly, one mutation made cells resistant to daratumumab but still responsive to isatuximab.

These findings suggest that CD38 loss or mutation is an important mechanism of resistance to therapy. They also highlight how genomic testing could help guide treatment decisions, especially when considering rechallenge with different CD38-targeting antibodies after relapse.
 

 

 

"Losing CD38 in myeloma"

Source

Maximilian Merz; Losing CD38 in myeloma. Blood 2025; 146 (13): 1529–1530. doi: https://doi.org/10.1182/blood.2025029889  September 25, 2025

Overview

In this commentary, Diamond and colleagues highlight how multiple myeloma can sometimes evade anti-CD38 antibody therapy through genetic changes in the CD38 gene, but they emphasize that most resistance is caused by subtler mechanisms like reduced antigen levels and immune system dysfunction rather than complete gene loss. Anti-CD38 antibodies such as daratumumab and isatuximab are widely used in myeloma treatment, yet resistance eventually develops in every patient, making it important to understand the underlying biology.

The study analyzed genomic data from over 800 patients, including newly diagnosed cases and relapsed patients with or without prior anti-CD38 therapy. Complete, biallelic loss of CD38 was rare, occurring in only about 6% of post-treatment cases. The researchers also found that monoallelic mutations can lower CD38 expression enough to weaken antibody binding, providing a mechanism for functional escape even without total gene loss. Laboratory studies confirmed that certain mutations reduced the effectiveness of both antibodies, while some mutations selectively impaired daratumumab but not isatuximab, suggesting genomic data could guide antibody choice in select patients.

Clinically, these findings show that while hard genetic loss of CD38 is uncommon, most relapsed patients still express the target but suffer from immune exhaustion and reduced antibody effectiveness. This reinforces the importance of strategies that boost CD38 expression, rejuvenate immune cells, or target alternative antigens like BCMA. For the small group with CD38 mutations, sequencing can help tailor therapy, and future antibody designs may overcome these specific genetic barriers. Overall, the study refines our understanding of resistance: sustaining both antigen expression and a functional immune response is key to keeping anti-CD38 therapy effective for most myeloma patients.
 

 

 

"Hepatitis E virus infections in people with multiple myeloma: an emerging challenge in the era of immunotherapeutic approaches"

Source

Al-Bazaz M, Pischke S, Alsdorf W, Sonnemann P, Cichutek S, Wiesch JS zur, Schaefers C, Artzenroth J, Leypoldt L, Kamili A, Bokemeyer C, Weisel K, Kosch R. Hepatitis E virus infections in people with multiple myeloma: an emerging challenge in the era of immunotherapeutic approaches. Haematologica; https://doi.org/10.3324/haematol.2025.288381 [Early view]. September 25, 2025.  

Overview

Hepatitis E virus (HEV) is an often-overlooked cause of viral hepatitis, and its incidence is rising in high-income countries, mainly through animal-to-human transmission. Patients with multiple myeloma are particularly vulnerable, yet guidance on antiviral treatment and how to manage myeloma therapy during infection is limited. This study describes seven myeloma patients in Western Europe who were diagnosed with HEV within a single year, confirmed by positive HEV RNA in blood.

While none of the patients developed severe liver failure, HEV caused significant disruptions to their care. Autologous stem cell transplants were postponed, CAR T-cell collection was delayed, and bispecific antibody treatments were suspended for up to five months. Four patients received ribavirin, but three undergoing T-cell-redirecting therapies—including CAR T-cell and bispecific antibody treatments—developed chronic HEV infection despite antiviral therapy. One patient, even after clearing the virus from blood, had persistent HEV in cerebrospinal fluid, causing ongoing neurological symptoms.

As the largest reported series of HEV infections in myeloma patients and the first to show chronic infection during T-cell-redirecting therapies, the study highlights the need for greater awareness of HEV. It also underscores the importance of screening patients before and during treatment, especially when liver enzyme levels rise unexpectedly, and the urgent need for standardized management strategies in the era of modern immunotherapies.
 

 

 

"Peroxiredoxins as novel indicators in multiple myeloma associated with ferroptosis and immune infiltration"

Source

Chen, Y., Peng, X., Feng, Z. et al. Peroxiredoxins as novel indicators in multiple myeloma associated with ferroptosis and immune infiltration. Sci Rep 15, 32765 (2025). https://doi.org/10.1038/s41598-025-17422-2  September 25, 2025. 

Overview

This study explored the role of the peroxiredoxin (PRDX) family of proteins in multiple myeloma, examining their potential as diagnostic and prognostic markers, their biological functions, and their impact on the immune system. Using large databases and bioinformatics tools, the researchers found that several PRDX proteins—especially PRDX2, 4, 5, and 6—are expressed at higher levels in myeloma cells compared with normal plasma cells. In relapsed patients, PRDX1, 2, 3, and 6 were even more strongly upregulated.

PRDX2 stood out as highly expressed and linked to aggressive tumor features and poorer outcomes. Functional experiments showed that silencing PRDX2 affected cell proliferation, immune cell infiltration, and susceptibility to ferroptosis, a type of cell death. Genes related to PRDX proteins are involved in key metabolic processes and may influence both ferroptosis and immune pathways in myeloma cells.

This is the first comprehensive study highlighting the diagnostic and prognostic relevance of the PRDX family in multiple myeloma. The findings suggest that targeting PRDX-related pathways, including ferroptosis and immune regulation, could offer new therapeutic strategies for treating the disease.
 

 

 

"Health-related quality of life and financial toxicity in Chinese patients with multiple myeloma: a two-year real-world multicentre study"

Source

Wu, W., Wang, Y., Wu, Y. et al. Health-related quality of life and financial toxicity in Chinese patients with multiple myeloma: a two-year real-world multicentre study. Health Qual Life Outcomes 23, 87 (2025). https://doi.org/10.1186/s12955-025-02419-2 September 26, 2025. 

Overview

This study explored the role of the peroxiredoxin (PRDX) family of proteins in multiple myeloma, examining their potential as diagnostic and prognostic markers, their biological functions, and their impact on the immune system. Using large databases and bioinformatics tools, the researchers found that several PRDX proteins—especially PRDX2, 4, 5, and 6—are expressed at higher levels in myeloma cells compared with normal plasma cells. In relapsed patients, PRDX1, 2, 3, and 6 were even more strongly upregulated.

PRDX2 stood out as highly expressed and linked to aggressive tumor features and poorer outcomes. Functional experiments showed that silencing PRDX2 affected cell proliferation, immune cell infiltration, and susceptibility to ferroptosis, a type of cell death. Genes related to PRDX proteins are involved in key metabolic processes and may influence both ferroptosis and immune pathways in myeloma cells.

This is the first comprehensive study highlighting the diagnostic and prognostic relevance of the PRDX family in multiple myeloma. The findings suggest that targeting PRDX-related pathways, including ferroptosis and immune regulation, could offer new therapeutic strategies for treating the disease.
 

 

 

"Newly Diagnosed High-Risk Multiple Myeloma: Outcomes and Management"

Source

Yasar, Fatma Zehra, Gorshein, Elan, Newly Diagnosed High-Risk Multiple Myeloma: Outcomes and Management, Advances in Hematology, 2025, 6622365, 16 pages, 2025. https://doi.org/10.1155/ah/6622365 September 26, 2025. 

Overview

Multiple myeloma is a complex blood cancer, and about 20%–25% of newly diagnosed patients carry high-risk cytogenetic abnormalities, such as del(17p), t(4;14), t(14;16), or gain(1q), which are linked to aggressive disease, frequent relapses, and poorer survival. This review examines current and emerging treatment strategies for these high-risk patients, including induction therapies for both transplant-eligible and transplant-ineligible patients, autologous stem cell transplantation, and consolidation and maintenance approaches.

Newer treatment options, such as quadruplet induction regimens that combine proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, are showing improved outcomes and are increasingly used in frontline therapy. The review also highlights the growing role of bispecific antibodies and CAR-T cell therapies, especially as these modalities move into earlier treatment lines. Personalized approaches that consider a patient’s cytogenetic profile and minimal residual disease status are becoming important for tailoring therapy. Ongoing clinical trials exploring early use of CAR-T and bispecific antibodies may further reshape how high-risk multiple myeloma is treated in the future.
 

 

 

"Transcriptome Analysis Identifies Functional and Prognostic Hypoxia-Associated Genes in Multiple Myeloma"

Source

L. Hou, J. Zhang, Q. Ran, Z. Li, and M. Chen, “ Transcriptome Analysis Identifies Functional and Prognostic Hypoxia-Associated Genes in Multiple Myeloma,” International Journal of Laboratory Hematology (2025): 1–10, https://doi.org/10.1111/ijlh.70009.  September 26, 2025. 

Overview

Multiple myeloma is an incurable blood cancer marked by the buildup of malignant plasma cells in the bone marrow. Research suggests that low oxygen levels, or hypoxia, in the bone marrow contribute to disease progression, but the mechanisms behind this effect are not fully understood. In this study, researchers analyzed gene expression in myeloma cell lines under hypoxia and in patient data from the MMRF CoMMpass project to identify hypoxia-associated genes (HAGs) relevant to the disease.

They found 17 genes in cell lines and 92 genes in patient samples that were affected by hypoxia, with nine genes overlapping between the two datasets. Several of these genes were linked to overall survival, and six were specifically associated with survival in the first year after diagnosis. Hypoxia scores calculated from these genes were higher in myeloma patients than in healthy individuals, indicating that low oxygen is a prominent feature of the bone marrow environment in this disease. Validation in additional patient samples confirmed that severe hypoxia affects plasma cells and other cell types in the bone marrow.

These findings suggest that hypoxia plays a key role in multiple myeloma progression and could help guide prognosis and the development of therapies targeting the low-oxygen environment in the bone marrow.
 

 

 

"The unmet psychological needs of people living with multiple myeloma and smouldering myeloma: a review of current approaches and future directions"

Source

Natalie Tuckey, Matthew Iasiello, Kathina Ali, Angelina Yong, Sophie Wilson, Mark Ryan, Dom Scoleri, Melissa Cantley, Hannah R Wardill, The unmet psychological needs of people living with multiple myeloma and smouldering myeloma: a review of current approaches and future directions, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.09.016. September 26, 2025. 

Overview

Multiple myeloma is the second most common blood cancer and remains incurable, requiring ongoing treatment to manage the disease. Patients often experience high levels of anxiety and depression, reporting some of the lowest quality of life among all cancer types. Despite this heavy psychological burden, interventions to support mental health in people with myeloma, smoldering myeloma, or its precursor, monoclonal gammopathy of undetermined significance, are limited.

Existing psychosocial programs are often small, short-term, and inconsistently designed, with few involving patients in their development. They rarely address the complex overlap of physical and psychological challenges, such as pain, fatigue, body image concerns, and uncertainty, and seldom integrate mental health support with exercise or rehabilitation programs. Caregivers, who also face significant emotional strain, are frequently overlooked.

This review highlights the urgent need for comprehensive, co-designed interventions that reflect the real experiences of patients and caregivers. Programs that address both physical and psychological needs and focus on sustainable implementation could improve mental health, reduce healthcare burden, and enhance overall supportive care for people living with myeloma.
 

 

 

"Management of relapsed refractory multiple myeloma: Evidence-based guide to community oncologists"

Source

Ali Mushtaq, Asfand Yar Cheema, Hossam M. Ali, Yara Shatnawi, Omer Ashruf, Eman Nayaz Ahmad, Olga Lytvynova, Mishaal Munir, Muhammad Anns Asif, Maheen Ahmad, Hamza Hassan, Abdullah M. Khan, Tara Roy, Aneela Majeed, Shahzad Raza, Sandra Mazzoni, Louis Williams, Jack Khouri, Jason Valent, Christy Samaras, Joslyn Rudoni, Beth M. Faiman, Mikhaila Rice, Jonathan Kissam, Diana Basali, Faiz Anwer, Management of relapsed refractory multiple myeloma: Evidence-based guide to community oncologists, Blood Reviews, 2025, 101339, ISSN 0268-960X, https://doi.org/10.1016/j.blre.2025.101339. September 27, 2025. 

Overview

Multiple myeloma is a cancer of plasma cells, and treating patients who experience early relapse after one to three prior therapy lines remains challenging. This review offers clinicians guidance for personalized, evidence-based treatment strategies for early relapsed or refractory multiple myeloma, taking into account patient factors like frailty and other health conditions, disease features such as high-risk cytogenetics, prior therapy response, and treatment tolerability.

The review covers current and emerging therapies, including monoclonal antibodies targeting CD38 and SLAMF7, BCMA-directed immunotherapies like CAR T cells and bispecific antibodies, and highlights key clinical trial results on efficacy and safety, including risks like cytokine release syndrome, neurotoxicity, and infections. It provides a practical framework for choosing between combination regimens and immunotherapy platforms, considering meaningful outcomes and survival. Strategies for managing relapse after BCMA-targeted therapy and potential salvage options are also discussed.

Looking ahead, the review emphasizes next-generation cellular therapies, novel antibody designs, CELMoDs, and approaches to enhance immunotherapy outcomes, offering a roadmap for optimizing care in early relapsed multiple myeloma.
 

 

 

"Real-World Efficacy Outcomes of Ciltacabtagene Autoleucel in Relapsed Refractory Multiple Myeloma: A Comparative Study with the Cartitude-1 Trial"

Source

Ishita Kamboj, Alma Habib, Darryl Chang, Aliya Rashid, Andrew Vegel, Kevin Graf, Emily Struble, Muhammad Umair Mushtaq, Zahra Mahmoudjafari, Kimberly Green, Abdullah Mohammad Khan, Christopher Sun Strouse, Joseph P McGuirk, Hamza Hashmi, Hira Shaikh, Shebli Atrash, Al-Ola Abdallah, Nausheen Ahmed, Real-World Efficacy Outcomes of Ciltacabtagene Autoleucel in Relapsed Refractory Multiple Myeloma: A Comparative Study with the Cartitude-1 Trial, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.09.015. September 28, 2025. 

Overview

The CARTITUDE-1 trial led to the approval of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T therapy, for patients with relapsed or refractory multiple myeloma after three or more prior treatments. To see how these results translate to everyday clinical practice, researchers conducted a retrospective analysis of 73 real-world patients treated with cilta-cel and compared them to 97 patients from the original trial. Baseline characteristics such as age, gender, race, prior therapies, and high-risk disease features were broadly similar, though real-world patients were generally less fit, had more extramedullary disease, and fewer were refractory to certain therapies. Nearly half of the real-world patients would not have met the original trial’s inclusion criteria.

Overall response rates were slightly lower in the real-world group (88% vs. 97%), but survival outcomes at two years, including progression-free and overall survival, were comparable. Interestingly, real-world patients experienced fewer treatment-related adverse events, suggesting better tolerability.

These findings show that cilta-cel is effective and safe in everyday clinical settings, supporting broader trial eligibility criteria that more accurately reflect real-world populations. This evidence can help optimize treatment strategies for patients with relapsed or refractory multiple myeloma.
 

 

 

"Refining PET-based response in extramedullary multiple myeloma using total lesion glycolysis"

Source

Zanwar, S., Belge Bilgin, G., Broski, S.M. et al. Refining PET-based response in extramedullary multiple myeloma using total lesion glycolysis. Leukemia (2025). https://doi.org/10.1038/s41375-025-02776-3 September 28, 2025. 

Overview

The CARTITUDE-1 trial led to the approval of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T therapy, for patients with relapsed or refractory multiple myeloma after three or more prior treatments. To see how these results translate to everyday clinical practice, researchers conducted a retrospective analysis of 73 real-world patients treated with cilta-cel and compared them to 97 patients from the original trial. Baseline characteristics such as age, gender, race, prior therapies, and high-risk disease features were broadly similar, though real-world patients were generally less fit, had more extramedullary disease, and fewer were refractory to certain therapies. Nearly half of the real-world patients would not have met the original trial’s inclusion criteria.

Overall response rates were slightly lower in the real-world group (88% vs. 97%), but survival outcomes at two years, including progression-free and overall survival, were comparable. Interestingly, real-world patients experienced fewer treatment-related adverse events, suggesting better tolerability.

These findings show that cilta-cel is effective and safe in everyday clinical settings, supporting broader trial eligibility criteria that more accurately reflect real-world populations. This evidence can help optimize treatment strategies for patients with relapsed or refractory multiple myeloma.
 

 

 

"The risk of second primary malignancies in patients receiving T-cell directed therapies for multiple myeloma: a systematic review"

Source

Park, H., Robinson, J., Flanagan, C., Pawlyn, C., Jackson, G., & Jones, J. R. (2025). The risk of second primary malignancies in patients receiving T-cell directed therapies for multiple myeloma: a systematic review. Leukemia & Lymphoma, 1–10. https://doi.org/10.1080/10428194.2025.2560085 September 29, 2025. 

Overview

T-cell-directed therapies, including CAR T-cell and bispecific antibody treatments, have transformed care for patients with triple-class refractory multiple myeloma, but long-term safety concerns remain, particularly the risk of developing second primary malignancies (SPMs). To better understand this risk, researchers systematically reviewed clinical trial and real-world studies reporting outcomes in patients receiving these therapies. They analyzed 12 studies encompassing 2,743 patients, most of whom received CAR T-cell therapy, with only one study on bispecific antibodies.

The pooled analysis estimated that about 6.3% of patients treated with CAR T cells developed SPMs, with blood cancers being the most common type. These findings highlight a potential long-term risk for patients undergoing T-cell-directed therapies. The authors emphasize the need for ongoing prospective trials and pharmacovigilance to better define the incidence and nature of SPMs in this patient population, ensuring safer long-term management for patients with relapsed or refractory multiple myeloma.
 

 

 

"Tumor-priming CD8+ natural killer T-like cells as an efficient novel cell therapy for relapsed/refractory multiple myelomaTumor-priming CD8+ natural killer T-like cells as an efficient novel cell therapy for relapsed/refractory multiple myeloma"

Source

Lee, J., Choi, E., Han, B. et al. Tumor-priming CD8+ natural killer T-like cells as an efficient novel cell therapy for relapsed/refractory multiple myeloma. Exp Hematol Oncol 14, 116 (2025). https://doi.org/10.1186/s40164-025-00707-7  September 29, 2025. 

Overview

Relapsed and refractory multiple myeloma remains difficult to treat, as most patients eventually relapse after standard therapies and have limited options. While BCMA-targeted CAR-T cells have shown strong efficacy in some patients, their widespread use is limited by reliance on patients’ own cells, long manufacturing times, high costs, and serious immune-related side effects. Researchers are therefore seeking safer, more accessible, and faster immunotherapy alternatives.

In this study, scientists developed a new immune cell product using cord blood mononuclear cells primed with tumor cells from myeloma patients. The resulting CD8+ NKT-like cells, called tumor-primed NKT-like cells (TPNC), showed strong cytotoxic activity and cytokine production against multiple myeloma cell lines and patient samples. These cells could kill tumor cells through both MHC-restricted and non-restricted pathways, rapidly form immune synapses, and perform serial killing. In mouse models, TPNC suppressed tumor growth, extended survival, and persisted in circulation without causing toxicity.

The researchers also applied this tumor-priming approach to leukemia, generating TPNC with potent activity against acute myeloid and lymphoblastic leukemia, comparable to anti-CD19 CAR-NK cells. These findings suggest that TPNC could become a scalable, personalized immunotherapy platform with strong anti-tumor activity and a favorable safety profile for multiple myeloma and other blood cancers.
 

 

 

"Current experiences with teclistamab in patients with multiple myeloma and renal impairment"

Source

Dimopoulos, M. A., Cohen, Y. C., Perrot, A., Pianko, M. J., Faber, E. A., Leung, N., … Nooka, A. K. (2025). Current experiences with teclistamab in patients with multiple myeloma and renal impairment. Expert Review of Hematology. https://doi.org/10.1080/17474086.2025.2567296 September 29, 2025. 

Overview

Renal impairment, defined as a creatinine clearance below 40 mL/min, affects up to half of patients with multiple myeloma and has historically been linked to poorer outcomes. Many clinical trials exclude patients with kidney problems, limiting access to novel therapies and making real-world data essential to guide treatment decisions. Teclistamab, a BCMA × CD3 bispecific antibody approved for triple-class exposed relapsed/refractory multiple myeloma, has been studied in this context.

Data from the MajesTEC-1 trial show that teclistamab is generally safe and effective in patients with mild-to-moderate renal impairment, with pharmacokinetic analyses indicating no clinically meaningful differences compared with patients without kidney issues. Early real-world reports also suggest that teclistamab can benefit patients with moderate-to-severe renal impairment, including those on dialysis, when proper precautions are taken.

These findings support the feasibility of teclistamab in multiple myeloma patients with renal impairment, but additional real-world studies and clinical trial data are needed to fully define its safety and efficacy in this high-risk population.
 

 

 

"Impact of residual clonal plasma cells in S-phase at the time of autologous stem cell transplantation on clinical outcomes"

Source

Hellou, T., Packard, D.G., Atallah-Yunes, S.A. et al. Impact of residual clonal plasma cells in S-phase at the time of autologous stem cell transplantation on clinical outcomes. Blood Cancer J. 15, 152 (2025). https://doi.org/10.1038/s41408-025-01349-y September 29, 2025. 

Overview

Autologous stem cell transplantation (ASCT) is an important treatment for multiple myeloma, but early relapses after transplant remain a major challenge. Researchers studied the S-phase percentage (S-phase%) of clonal plasma cells in the bone marrow at the time of ASCT using the plasma cell proliferation (PCPRO) test, which measures how many plasma cells are actively dividing. This marker provides a scalable alternative to older methods for assessing plasma cell proliferation.

In a retrospective analysis of 1,136 patients at Mayo Clinic, those with an S-phase% of 2% or higher had more high-risk disease features, including adverse cytogenetics, advanced ISS stage, and elevated creatinine. Their outcomes were significantly worse, with a median progression-free survival of 26 months and overall survival of 57 months, compared to 47 months and not reached, respectively, in patients with S-phase% below 2%. Patients with extremely high S-phase% (≥5% or ≥10%) had very poor outcomes, with median progression-free survival of just 13 and 3.5 months.

These findings show that S-phase% at ASCT is a strong prognostic marker and can identify patients unlikely to benefit from standard transplant. For these high-risk patients, alternative strategies, including enrollment in clinical trials of novel immunotherapies such as CAR T-cells or T-cell engagers, should be considered as part of first-line therapy.
 

 

 

"Discovery of Y502-2304, a potent c-Myc G-quadruplex stabilizer for the treatment of multiple myeloma"

Source

Jian Gao, Xinxin Qu, Mengting Li, Pingting Jia, Guanghui Cheng, Jiacheng Yin, Discovery of Y502-2304, a potent c-Myc G-quadruplex stabilizer for the treatment of multiple myeloma, European Journal of Medicinal Chemistry, 2025, 118209, ISSN 0223 5234, https://doi.org/10.1016/j.ejmech.2025.118209. September 30, 2025.  

Overview

c-Myc is a gene that drives cancer growth and is often overactive in multiple myeloma, contributing to poor outcomes. Directly targeting c-Myc with drugs has been difficult because it lacks obvious binding sites. Researchers focused on a G-quadruplex (G4) structure in the c-Myc promoter, which can be stabilized to suppress c-Myc activity. Using a virtual screen of small molecules, they identified a compound called Y502-2304 that selectively stabilizes the c-Myc G4 and strongly inhibits the growth of multiple myeloma cells.

Y502-2304 reduces c-Myc mRNA and protein levels, triggers apoptosis in myeloma cells, increases DNA damage signals, generates reactive oxygen species, and disrupts mitochondria. It also activates the p53 pathway and boosts pro-apoptotic proteins Noxa and PUMA. In mouse models, Y502-2304 effectively slowed tumor growth without noticeable toxicity. These results highlight Y502-2304 as a promising new therapy that selectively targets c-Myc through G4 stabilization and could offer a novel approach for treating multiple myeloma.
 

 

 

"Predictors of quality of life in multiple myeloma patients: a multi-centered cross-sectional study"

Source

Abu Hamdeh, N., Alnees, M., Ewidat, O. et al. Predictors of quality of life in multiple myeloma patients: a multi-centered cross-sectional study. BMC Cancer 25, 1472 (2025). https://doi.org/10.1186/s12885-025-14960-w  September 30, 2025.   

Overview

Multiple myeloma (MM) significantly reduces patients’ quality of life, but data from low- and middle-income countries are limited. In a study of 202 MM patients in the West Bank, Palestine, researchers used a validated Arabic questionnaire to assess health-related quality of life and identify key factors affecting it. They found that specific symptoms—including abdominal pain, chest pain, and swelling—were strong predictors of worse treatment-related side effects. Comorbidities such as gout and peptic ulcer disease negatively influenced patients’ body image, while chest pain also affected how patients viewed their future outlook. These results emphasize the need for supportive care that not only manages myeloma symptoms but also addresses coexisting health conditions, especially in healthcare settings with limited resources.
 

 

 

"Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma"

Source

Chen, W., Fu, C., Fang, B. et al. Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma. Exp Hematol Oncol 14, 119 (2025). https://doi.org/10.1186/s40164-025-00710-y  September 30, 2025.   

Overview

Zevorcabtagene autoleucel (zevor-cel) is a fully human CAR T-cell therapy approved in China for patients with relapsed or refractory multiple myeloma (RRMM) who have received at least three prior treatments. In the phase 2 LUMMICAR STUDY 1, 102 patients received zevor-cel and achieved a high overall response rate of 92%, with nearly 69% reaching stringent complete response. After a median follow-up of just over 20 months, progression-free and overall survival data are still maturing. Most patients experienced cytokine release syndrome, though severe cases were uncommon, and serious neurotoxicity was rare. These results show that zevor-cel provides deep, durable responses in heavily pre-treated RRMM patients with a manageable safety profile.
 

 

 

"Treatment-related cognitive changes in multiple myeloma: A systematic review and meta-analysis"

Source

Sumayyah Patel, Christopher Parrish, Frances Seymour, Melanie Burke, Treatment-related cognitive changes in multiple myeloma: A systematic review and meta-analysis, Journal of Geriatric Oncology, Volume 16, Issue 7, 2025, 102321, ISSN 1879-4068, https://doi.org/10.1016/j.jgo.2025.102321. September 2025.    

Overview

Multiple myeloma (MM) is an incurable blood cancer, and while advances in treatment have improved survival, the effects of these therapies on cognition are not well understood. This systematic review analyzed 18 studies including over 5,800 patients, with eight studies contributing to a meta-analysis of cognitive changes in the first six months of treatment. Results showed a significant decline in cognitive function during this early treatment period, based on objective assessments and self-reported measures. The review also noted potential self-selection bias, suggesting that study participants may not fully represent the broader MM population. Overall, these findings indicate that patients with MM may experience meaningful cognitive changes soon after starting therapy, highlighting the need for monitoring and supportive strategies.
 

 

 

"Analysis of the expression profile and biological function of plasma miRNAs in chronic lymphocytic leukemia and multiple myeloma patients occupationally exposed to pesticides"

Source

Luiza Flavia Veiga Francisco, Willian Garcia Birolli, Welinton Hirai, Caroline Rocha Nunes, Iara Zapparoli Gonçalves, Fabiana de Lima Vazquez, Álvaro José dos Santos Neto, Fernando Barbosa Junior, Márcia Maria Chiquitelli Marques, Henrique C.S. Silveira, Analysis of the expression profile and biological function of plasma miRNAs in chronic lymphocytic leukemia and multiple myeloma patients occupationally exposed to pesticides, Ecotoxicology and Environmental Safety, Volume 302, 2025, 118627, ISSN 0147-6513, https://doi.org/10.1016/j.ecoenv.2025.118627. September 2025. 

Overview

This study explored how occupational pesticide exposure affects microRNA (miRNA) profiles in patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Researchers analyzed plasma-derived miRNAs from 24 patients in Brazil using Nanostring technology, comparing those exposed and unexposed to pesticides. They found several miRNAs were downregulated (including miR-423‑3p, miR-1193, and miR-576‑5p) and others upregulated (such as miR-301b‑5p) in exposed patients. Network analysis suggested these miRNAs regulate key signaling pathways, including PI3K/Akt/mTOR and MAPK, and may also be linked to increased risk of neurological disorders and various cancers. This is the first study to show that pesticide exposure alters plasma miRNA expression in CLL and MM, highlighting these miRNAs as potential biomarkers for environmental impacts on blood cancers.
 

 

 

"Bispecific T-cell engager therapy for multiple myeloma"

Source

Diana Cirstea, Benjamin Puliafito, Bridget E. Kim, Matt Lei, Noopur Raje, Bispecific T-cell engager therapy for multiple myeloma, Best Practice & Research Clinical Haematology, Volume 38, Issue 3, 2025, 101649, ISSN 1521-6926, https://doi.org/10.1016/j.beha.2025.101649. September 2025. 

Overview

This review highlights the emerging role of T-cell engager (TCE) therapies in multiple myeloma (MM), especially for patients who relapse after standard treatments including triplet- or quadruplet-based regimens, autologous stem cell transplant (ASCT), and maintenance lenalidomide. TCEs, such as teclistamab, elranatamab, and talquetamab, provide off-the-shelf immunotherapy with impressive response rates and prolonged remissions in heavily pretreated patients, earning FDA approval. The article discusses key aspects of TCE design, strategies to overcome resistance, and the potential benefits of using TCEs earlier in the treatment course to deepen and extend responses. Outpatient step-up dosing (SUD) is also noted as a practical approach to facilitate broader adoption in community settings.
 

 

 

"Adoptive cellular therapies in multiple myeloma"

Source

David Kegyes, Bogdan Borlea, Marc Damian, Adrian Bogdan Tigu, Madalina Nistor, Diana Cenariu, Raluca Munteanu, Diana Gulei, Angela Dascalescu, Ion Antohe, Alina Tanase, Evangelos Terpos, Hermann Einsele, Ciprian Tomuleasa, Adoptive cellular therapies in multiple myeloma, Best Practice & Research Clinical Haematology,Volume 38, Issue 3, 2025, 101638, ISSN 1521-6926, https://doi.org/10.1016/j.beha.2025.101638. September 2025. 

Overview

This article reviews the evolving landscape of CAR T-cell and NK-cell therapies for multiple myeloma, a blood cancer driven by clonal plasma cell proliferation in the bone marrow. It highlights the successful use of adoptive cellular therapies in relapsed or refractory patients and growing evidence supporting their earlier use, potentially as an alternative to autologous stem cell transplantation. The review also discusses ongoing research aimed at expanding CAR therapy to solid tumors and improving safety and efficacy through innovative designs and combination strategies, providing a comprehensive overview of the latest advancements in cellular immunotherapy for plasma cell myeloma.
 

 

 

"Advances in NK cell therapy for multiple myeloma"

Source

Najing Liu, Yujin Zeng, Ying Wang, Congyue Wang, Nuoxian Li, Jinge Xu, Advances in NK cell therapy for multiple myeloma, Best Practice & Research Clinical Haematology, Volume 38, Issue 3, 2025, 101639, ISSN 1521-6926, https://doi.org/10.1016/j.beha.2025.101639. September 2025.  

Overview

This article reviews the role of natural killer (NK) cells in multiple myeloma, a cancer marked by abnormal proliferation of clonal plasma cells. It highlights how MM suppresses both the number and function of NK cells, reducing immune surveillance and allowing disease progression. The review covers current treatment strategies aimed at restoring or enhancing NK cell activity, including adoptive NK cell therapy and CAR-NK therapy, and summarizes the latest preclinical and clinical findings, emphasizing the potential of NK cell–based immunotherapy as a promising approach in MM management.
 

 

 

"Deep learning differentiates multiple myeloma from plasmablastic lymphoma"

Source

Lucas Lacerda de Souza, Marco Magalhaes, Ahmed Hagag, Pablo Agustin Vargas, Deep learning differentiates multiple myeloma from plasmablastic lymphoma, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 140, Issue 3, 2025, Page e117, ISSN 2212-4403, https://doi.org/10.1016/j.oooo.2025.04.152. September 2025. 

Overview

This study explores the use of deep learning to improve diagnostic accuracy between plasmablastic lymphoma (PL) and multiple myeloma (MM), two diseases with overlapping features that complicate clinical decision-making. Whole slide images from 61 patients were segmented into image patches and used to train deep learning models, including ResNet50, InceptionV3, ConvNeXtXLarge, and EfficientUnet. Results showed strong performance, with ConvNeXtXLarge achieving 95% accuracy and EfficientUnet reaching the highest F1-score of 0.97. These findings highlight the potential of advanced AI algorithms to enhance the pathology-based diagnosis of plasma cell neoplasms, with future efforts aimed at expanding datasets and refining models for broader clinical use.
 

 

 

"Biphasic behavior of T cell subsets reflects failure of early anti-myeloma response and leads to progressive T cell dysfunction"

Source

Suchita Suryakant Jadhav, Vipin Sharma, Aharon Lion, Lasser-Katz Efrat, Iftach Shaked, Galia Luboshits, Michael A. Firer, Biphasic behavior of T cell subsets reflects failure of early anti-myeloma response and leads to progressive T cell dysfunction, Neoplasia, Volume 67, 2025, 101208, ISSN 1476-5586, https://doi.org/10.1016/j.neo.2025.101208. September 2025. 

Overview

This study investigates how immune system dysfunction contributes to the development of multiple myeloma (MM) using a long-term mouse model. Balb/c mice were inoculated with myeloma cells and monitored over 220 days, with blood and bone marrow samples collected at multiple time points. Blood analyses confirmed features similar to human MM, while bone marrow profiling revealed a biphasic pattern in T regulatory cells, Th17 cells, CD8+ T cells, and NK cells, alongside altered memory T-cell distributions. These findings indicate an early anti-myeloma response that eventually gives way to immunosuppression and CD8+ T-cell exhaustion. This model provides a valuable tool for studying early immune changes in MM and for testing new therapeutic strategies.
 

 

 

"ALKBH5 reverses romidepsin-mediated anti-multiple myeloma activity via regulation of m6A modification of FOXM1"

Source

Yaxin Zhang, Xu Cao, Wenjing Li, Zeyu Cui, Jiwei Mao, Ruosi Yao, Linlin Liu, ALKBH5 reverses romidepsin-mediated anti-multiple myeloma activity via regulation of m6A modification of FOXM1, Biochemical Pharmacology, Volume 239, 2025, 116998, ISSN 0006-2952, https://doi.org/10.1016/j.bcp.2025.116998. September 2025. 

Overview

This study explores the role of ALKBH5, an RNA demethylase, in multiple myeloma (MM) and its interaction with the histone deacetylase inhibitor romidepsin. Elevated ALKBH5 levels were associated with poor prognosis in MM, and romidepsin was found to inhibit both its protein levels and enzymatic activity. While ALKBH5 overexpression did not affect cell viability directly, it reduced romidepsin-induced apoptosis, whereas ALKBH5 knockout enhanced apoptotic effects. Mechanistically, ALKBH5 stabilized FOXM1 mRNA by reducing m6A methylation, promoting protein translation, while romidepsin increased m6A methylation, accelerating FOXM1 decay. In vivo xenograft models confirmed that ALKBH5 diminishes romidepsin’s anti-myeloma activity. These findings suggest that combining romidepsin treatment with ALKBH5 inhibition may enhance therapeutic efficacy in MM.
 

 

 

"Increased LDH Remains a Crucial Prognostic Factor in Patients With Multiple Myeloma"

Source

Ramiro Espinoza-Zamora, Nidia Paulina Zapata-Canto, Lizbeth Deyanir Aguilera-Urbina, Judith Cruz-Velazquez, Elba Reyes-Maldonado, Jorge Vela-Ojeda, Increased LDH Remains a Crucial Prognostic Factor in Patients With Multiple Myeloma, Archives of Medical Research, Volume 56, Issue 6, 2025, 103239, ISSN 0188-4409, https://doi.org/10.1016/j.arcmed.2025.103239. September 2025.  

Overview

This study examined prognostic factors in 286 patients with newly diagnosed multiple myeloma, focusing on accessible clinical, laboratory, and cytogenetic markers. Patients received either thalidomide-based (64.5%) or proteasome inhibitor-based (35.5%) treatment regimens. Outcomes showed that stringent complete remission was achieved in 15.5%, complete remission in 30.5%, very good partial response in 41%, and partial response in 5%. Progression-free and overall survival were lower in patients with high lactate dehydrogenase (LDH), renal disease, t(4;14) translocation, RB1 mutation, or those who did not achieve complete remission or receive transplantation and proteasome inhibitors. Elevated LDH emerged as the strongest independent prognostic factor. The study also proposed a simple scoring system combining LDH, renal disease, t(4;14), and RB1 mutation to stratify patients by risk, offering a practical tool for centers with limited access to advanced cytogenetic testing.
 

 

 

"Altered dynamics of T cell subsets in peripheral blood impacts disease progression in newly diagnosed multiple myeloma"

Source

Mohini Vig, Lalit Kumar, Shweta Dubey, Ritu Gupta, Altered dynamics of T cell subsets in peripheral blood impacts disease progression in newly diagnosed multiple myeloma, Biochemistry and Biophysics Reports, Volume 43, 2025, 102104, ISSN 2405-5808, https://doi.org/10.1016/j.bbrep.2025.102104. September 2025.   

Overview

This study investigated the role of T cells in newly diagnosed multiple myeloma (NDMM) by analyzing T cell subsets, activation status, and inhibitory receptor expression in 40 patients. Compared to healthy controls, NDMM patients showed reduced T cell numbers, an imbalance between naïve and effector CD4+ T cells, and decreased memory regulatory T cells (Tregs). Circulating follicular helper T cells (cTFH) and inhibitory receptor–expressing T cells correlated with plasma cell levels in the bone marrow, suggesting that disrupted T cell homeostasis and immune dysregulation may contribute to disease progression in multiple myeloma.
 

 

 

"A comprehensive targeted panel of 295 genes: Unveiling key disease initiating and transformative biomarkers in multiple myeloma"

Source

Vivek Ruhela, Ritu Gupta, Rupin Oberoi, Anubha Gupta, A comprehensive targeted panel of 295 genes: Unveiling key disease initiating and transformative biomarkers in multiple myeloma, Computers in Biology and Medicine, Volume 196, Part A, 2025, 110619, ISSN 0010-4825, https://doi.org/10.1016/j.compbiomed.2025.110619. September 2025.    

Overview

This study developed a novel AI-driven framework, BIO-DGI, to distinguish multiple myeloma (MM) from its precursor, monoclonal gammopathy of undetermined significance (MGUS), by integrating multi-variant genomic data and gene-gene interactions. Using SNVs, CNVs, and SVs from whole-exome and whole-genome sequencing, the model outperformed traditional machine learning methods in identifying MM-relevant genes. Post-hoc analyses, including ShAP, community analysis, survival assessment, and pathway enrichment, guided the creation of a clinically validated 295-gene panel strongly associated with MM-related biological pathways. This approach provides a powerful tool for early detection, biomarker discovery, and deeper understanding of MM pathogenesis.
 

 

 

"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, Adam D. Cohen, Jalpa A. Doshi, David L. Porter, Alfred L. Garfall, Edward A. Stadtmauer, Carmen E. Guerra, Sandra 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; 1 (2): 100007. doi: https://doi.org/10.1016/j.bict.2025.100007  September 17, 2025. 

Overview

This study examined access and outcomes of CAR T-cell therapy targeting BCMA (CART-BCMA) in multiple myeloma (MM) patients, focusing on racial and ethnic minority populations (REMPs). Across multiple cohorts, REMPs were consistently underrepresented among those receiving CART-BCMA, highlighting disparities in access. Despite this, REMP patients who received therapy had comparable clinical outcomes to non-REMP patients, including similar rates of very good partial response, progression-free survival, overall survival, and safety profiles. These findings underscore that while CART-BCMA is effective and safe for all patients, targeted efforts are needed to ensure equitable access for underrepresented populations.