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 June 2024 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 June 2024) 

"Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma"

Source

Meletios Athanasios Dimopoulos, Meral Beksac, Ludek Pour et al. Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma. New England Journal of Medicine. doi:10.1056/NEJMoa2403407. https://www.nejm.org/doi/full/10.1056/NEJMoa2403407. June 2, 2024. 

Overview

Current treatments for multiple myeloma help patients live longer, but the cancer often comes back. Researchers tested a new combination of drugs to see if it could help patients whose cancer returned after initial treatment.

In this study, 302 patients took part. Half received a new drug combination (BPd, and half received a standard drug combination (PVd). After one year, 71% of patients on BPd had no cancer growth, compared to 51% on PVd. Also, more patients on BPd had their cancer shrink or disappear. Unfortunately, the BPd caused more side effects, especially eye problems. Yet, these eye problems could be managed by changing the dose of one drug. Researchers concluded that the new drug combination (BPd) worked better at stopping cancer growth and shrinking tumors. It caused more side effects, but these could be controlled. This treatment might help patients whose cancer has come back after other treatments.

 

 

"CD8+ CD28− regulatory T cells after induction therapy predict progression-free survival in myeloma patients: results from the GMMG-HD6 multicenter phase III study"

Source

Kriegsmann, K., Ton, G.N.H.Q., Awwad, M.H.S. et al. CD8+ CD28− regulatory T cells after induction therapy predict progression-free survival in myeloma patients: results from the GMMG-HD6 multicenter phase III study. Leukemia (2024). https://doi.org/10.1038/s41375-024-02290-y  June 3, 2024.  

Overview

From this letter to the editor: "This study aims to delve deeper into the impact of elotuzumab on T cell subsets within the multiple myeloma microenvironment to elucidate its prognostic implications and refine therapeutic strategies. Within the context of the GMMG-HD6 trial, we performed a planned subgroup-analysis on SLAMF7 high expressing T cell subsets."

 

 

"Inference of genomic lesions from single-cell RNAseq in myeloma improves functional intra- and inter-clonal analysis"

Source

Francesca Lazzaroni, Antonio Matera, Alessio Marella, Akihiro Maeda, Giancarlo Castellano, Alfredo Marchetti, Sonia Fabris, Stefania Pioggia, Ilaria Silvestris, Domenica Ronchetti, Silvia Lonati, Giuseppina Fabbiano, Valentina Traini, Elisa Taiana, Laura Porretti, Federico Simone Colombo, Claudio De Magistris, Margherita Scopetti, Marzia Barbieri, Loredana Pettine, Federica Torricelli, Antonino Neri, Francesco Passamonti, Marta Lionetti, Matteo Claudio Da Via', Niccolò Bolli; Inference of genomic lesions from single-cell RNAseq in myeloma improves functional intra- and inter-clonal analysis. Blood Adv 2024; bloodadvances.2023012409. doi: https://doi.org/10.1182/bloodadvances.2023012409  June 3, 2024  

Overview

Key Points from this study:

• single-cell RNAseq data can be used to infer the presence of the major cytogenetic alterations in multiple myeloma 
• single-cell B-cell receptor profiling along with copy-number and transcriptome improves functional dissection of myeloma subclones 

 

 

"Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial"

Source

Leleu, X., Hulin, C., Lambert, J. et al. Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-03050-2 June 3, 2024 

Overview

Currently, the best treatment for older multiple myeloma patients who are not eligible for transplant is the combination of the three drugs: isatuximab, lenalidomide, and dexamethasone. In this study, researchers wanted to see if adding a fourth drug, bortezomib, would make the treatment work even better. They did a study with 270 patients aged 65-79 who had just been diagnosed with multiple myeloma.

The main thing they looked at was how many patients had no cancer cells left after 18 months of treatment. They found that:

• With the three-drug treatment, 26% of patients had no detectable cancer cells.
• With the four-drug treatment (adding bortezomib), 53% of patients had no detectable cancer cells.

This big difference shows that adding bortezomib made the treatment much more effective. The four-drug combo also led to better overall responses in patients.

After about two years of follow-up, there wasn't a clear difference in how long patients lived, but it's too early to tell for sure.

Adding bortezomib didn't cause major problems with the other drugs in the treatment. Based on these results, the researchers think this new four-drug combination should be the new standard treatment for older patients with newly diagnosed multiple myeloma who can't have a transplant.

 

 

"Extended DaraKRd: Are we enhancing outcomes by prolonging treatment?"

Source

Schmidt, T.M. Extended DaraKRd: Are we enhancing outcomes by prolonging treatment?. Blood Cancer J. 14, 93 (2024). https://doi.org/10.1038/s41408-024-01070-2  June 4, 2024. 

Overview

Researchers tested a new four-drug treatment for newly diagnosed multiple myeloma, a type of blood cancer. The treatment combines daratumumab, carfilzomib, lenalidomide, and dexamethasone (called DaraKRd for short) for two years, followed by ongoing lenalidomide.

The results were very good:

• 75% of patients had no detectable cancer after 8 cycles of treatment
• After 3 years, 85% of patients still had no cancer progression
• 95% of patients were still alive after 3 years
• No patients stopped treatment due to side effects

While these results are exciting, there are some things to keep in mind:

• The study mostly included younger, healthier patients
• Researchers don't know if this treatment is better than other options
• It's unclear if this approach is right for patients with very high-risk myeloma

The researchers also tested new ways to check for remaining cancer cells in the blood. These blood tests might help doctors make treatment decisions in the future without needing as many painful bone marrow biopsies.

Overall, this study shows that DaraKRd is a strong treatment option for many patients with newly diagnosed multiple myeloma. However, more research is needed to determine the best treatment approach for different groups of patients.

 

 

"t(11;14) status is stable between diagnosis and relapse and concordant between detection methodologies based on fluorescence in situ hybridization and next-generation sequencing in patients with multiple myeloma"

Source

Avet-Loiseau H, Thiébaut-Millot R, Li X, Ross JA, Hader C. t(11;14) status is stable between diagnosis and relapse and concordant between detection methodologies based on fluorescence in situ hybridization and next-generation sequencing in patients with multiple myeloma. Haematologica 2024;109(6):1874-1881; https://doi.org/10.3324/haematol.2023.284072. Vol. 109 No. 6 (2024): June 2024 . 

Overview

This study looked at a specific genetic change called t(11;14) in multiple myeloma patients. Here's what the researchers found:

1. They checked if t(11;14) stays the same over time in MM patients. They looked at 272 patients when they were first diagnosed and after their cancer came back.
2. All patients kept the same t(11;14) status throughout their illness. If they had it at the start, they still had it later. If they didn't have it at the start, they still didn't have it later.
3. The researchers used two different ways to test for t(11;14): FISH and NGS. Both methods gave the same results for all 130 patients they tested.
4. Patients with t(11;14) had fewer overall genetic changes than those without it.
5. Some genes were more likely to be changed in patients with t(11;14), while others were less likely.

This study shows that t(11;14) stays stable in myeloma patients over time. This information could help doctors better understand and treat the disease.

 

 

"Real-world multiple myeloma risk factors and outcomes by non-Hispanic Black/African American and non- Hispanic White race/ethnicity in the United States"

Source

Buck T, Hartley-Brown MA, Efebera YA, Milner CP, Zonder JA, Richardson PG, Salinardi T, Rice MS. Real-world multiple myeloma risk factors and outcomes by non-Hispanic Black/African American and non- Hispanic White race/ethnicity in the United States. Haematologica 2024;109(6):1882-1892; https://doi.org/10.3324/haematol.2023.282788. Vol. 109 No. 6 (2024): June, 2024 

Overview

Researchers looked at how race affects people with multiple myeloma. They studied Black and White patients in the United States who were diagnosed between 2016 and 2022.

Key findings:

• About 23% of participants were Black patients.
• These Black patients were usually younger and more often female.
• Both groups had similar rates of high-risk genetic features.
• The most common treatment was the same for both groups. 
• Fewer Black patients had stem cell transplant.
• Without adjusting for other factors, survival rates were similar..
• After adjusting for other factors, Black patients had slightly worse outcomes, but the difference was small.

This study helps doctors understand how race might affect multiple myeloma treatment and results. It shows that while there are some differences between Black and White patients, many aspects of the disease and its treatment are similar for both groups.

 

 

"Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma"

Source

Chong PS, Chooi JY, Lim SLJ, Chung T-H, Brunmeir R, Leow ACY, Toh SHM, Balan K, Azaman MIB, Wu Z, Subramaniam N, Vardy LA, Chng W-J. Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma. Haematologica 2024;109(6):1893-1908; https://doi.org/10.3324/haematol.2023.283467. Vol. 109 No. 6 (2024): .June 2024 

Overview

Scientists have found a new protein called REIIBP that plays a role in multiple myeloma. This protein is made by a gene that's changed in about 15% of patients with multiple myeloma. These patients often have a worse outlook.

REIIBP works by changing how genes are turned on or off. It does this by adding chemical tags to proteins that wrap around DNA. These tags can either activate or silence genes.

The researchers discovered that REIIBP turns on genes that cause inflammation in the body. This leads to the activation of other proteins that help cancer cells grow and resist treatment.

Importantly, the team found that a drug called Ibrutinib can target this process. In lab tests, this drug helped make cancer cells more sensitive to other treatments.

This research gives scientists a new way to think about treating multiple myeloma, especially for patients with this specific gene change. It suggests that targeting REIIBP and the processes it controls could lead to better treatments in the future.

 

 

"Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection"

Source

Lakhwani S, Rosiñol L, Puig N, Pico-Picos M-A, Medina-González L, Martínez-López J, Paiva B, Cedena M-T, Oriol A, Ríos-Tamayo R, Blanchard M-J, Jarque I, Bargay J, Moraleda J-M, Carrillo-Cruz E, Sureda A, Krsnik I, González E, Casado LF, Martí JM, Encinas C, De Arriba F, Palomera L, Sampol A, González-Montes Y, Motlló C, De La Cruz J, Alonso R, Mateos M-V, Bladé J, Lahuerta J-J, San-Miguel J, Hernández M-T. Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection. Haematologica 2024;109(6):1909-1917; https://doi.org/10.3324/haematol.2023.284154. Vol. 109 No. 6 (2024): June, 2024 

Overview

Multiple myeloma affects the immune system. Doctors can measure how well a patient's immune system is working by looking at certain proteins in their blood. This is called immunoparesis (IP).

This new study looked at two ways to measure IP in newly diagnosed multiple myeloma patients who can have a stem cell transplant:

1. The classic method, which measures total immunoglobulin levels
2. A newer method called Hevylite®, which looks at specific parts of immunoglobulins

The study wanted to see if patients who recovered from IP had better outcomes. They checked patients' blood after initial treatment and again after a year of maintenance therapy.

Key findings:

• Right after initial treatment, there was no difference in how long patients stayed cancer-free, regardless of which IP measuring method was used.
• After a year of maintenance therapy, patients who recovered from IP (measured by Hevylite®) stayed cancer-free longer than those who didn't recover.
• The Hevylite® method of measuring IP recovery was better at predicting outcomes than the classic method.
• Combining IP recovery information with another test called minimal residual disease (MRD) gave doctors a better idea of a patient's risk.

Checking if a patient recovers from IP using the Hevylite® method after a year of maintenance therapy can help predict how well they will do. This information, along with MRD testing, can help doctors make better treatment decisions for multiple myeloma patients.

 

 

"ctDNA improves prognostic prediction for patients with relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone"

Source

Yasunori Kogure, Hiroshi Handa, Yuta Ito, Masaki Ri, Yuichi Horigome, Masaki Iino, Yoriko Harazaki, Takahiro Kobayashi, Masahiro Abe, Tadao Ishida, Shigeki Ito, Hiromi Iwasaki, Junya Kuroda, Hirohiko Shibayama, Kazutaka Sunami, Hiroyuki Takamatsu, Hideto Tamura, Toshiaki Hayashi, Kiwamu Akagi, Tomohiro Shinozaki, Takahiro Yoshida, Ikuo Mori, Shinsuke Iida, Takahiro Maeda, Keisuke Kataoka; ctDNA improves prognostic prediction for patients with relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone. Blood 2024; 143 (23): 2401–2413. doi: https://doi.org/10.1182/blood.2023022540  June 6, 2024  

Overview

Researchers studied genetic changes in blood cancer cells from patients with hard-to-treat multiple myeloma. They looked at DNA from bone marrow cells and circulating tumor DNA (ctDNA) in the blood of 261 patients. All patients received the same treatment.

The study found:

• Some genetic changes were only in ctDNA, not bone marrow cells. This suggests these changes might be in smaller groups of cancer cells.
• Certain genetic changes, especially in genes like KRAS and TP53, were linked to worse outcomes for patients.
• The number of genetic changes in ctDNA was a strong predictor of how well patients would do. More changes meant worse outcomes.
• Using this information, along with other factors, researchers created a tool to predict patient outcomes.
• Some genetic changes, like those in TP53 and KRAS genes, often appeared after treatment started.

The researchers concluded that looking at genetic changes in ctDNA can better predict how patients will respond to treatment compared to only looking at bone marrow cells. This could help doctors make better treatment decisions for patients with hard-to-treat multiple myeloma.

 

 

"ctDNA improves prognostic prediction for patients with relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone"

Source

Yasunori Kogure, Hiroshi Handa, Yuta Ito, Masaki Ri, Yuichi Horigome, Masaki Iino, Yoriko Harazaki, Takahiro Kobayashi, Masahiro Abe, Tadao Ishida, Shigeki Ito, Hiromi Iwasaki, Junya Kuroda, Hirohiko Shibayama, Kazutaka Sunami, Hiroyuki Takamatsu, Hideto Tamura, Toshiaki Hayashi, Kiwamu Akagi, Tomohiro Shinozaki, Takahiro Yoshida, Ikuo Mori, Shinsuke Iida, Takahiro Maeda, Keisuke Kataoka; ctDNA improves prognostic prediction for patients with relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone. Blood 2024; 143 (23): 2401–2413. doi: https://doi.org/10.1182/blood.2023022540  June 6, 2024  

Overview

Researchers studied genetic changes in blood cancer cells from patients with hard-to-treat multiple myeloma. They looked at DNA from bone marrow cells and circulating tumor DNA (ctDNA) in the blood of 261 patients. All patients received the same treatment.

The study found:

• Some genetic changes were only in ctDNA, not bone marrow cells. This suggests these changes might be in smaller groups of cancer cells.
• Certain genetic changes, especially in genes like KRAS and TP53, were linked to worse outcomes for patients.
• The number of genetic changes in ctDNA was a strong predictor of how well patients would do. More changes meant worse outcomes.
• Using this information, along with other factors, researchers created a tool to predict patient outcomes.
• Some genetic changes, like those in TP53 and KRAS genes, often appeared after treatment started.

The researchers concluded that looking at genetic changes in ctDNA can better predict how patients will respond to treatment compared to only looking at bone marrow cells. This could help doctors make better treatment decisions for patients with hard-to-treat multiple myeloma.

 

 

"Blood, the hidden side of myeloma?"

Source

Jill Corre; Blood, the hidden side of myeloma?. Blood 2024; 143 (23): 2344–2345. doi: https://doi.org/10.1182/blood.2024024414 June 6, 2024 

Overview

This is a commentary on "ctDNA improves prognostic prediction for patients with relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone" In this commentary, researchers discuss finding new ways to predict how well patients with multiple myeloma will respond to treatment.

Researchers looked at DNA from tumor cells floating in patients' blood. This is called circulating tumor DNA (ctDNA). They found that certain genetic changes in the ctDNA could help predict how patients would do after treatment.

Two important genes they looked at were TP53 and KRAS. When these genes had mutations (changes), patients often didn't do as well. The more mutations found, the worse the outlook tended to be.

Interestingly, some genetic changes were only found in the blood samples, not in bone marrow samples. This suggests that blood tests might give a more complete picture of the cancer than bone marrow tests alone.

The researchers created a scoring system based on the number of mutations found in the blood. This system could help doctors figure out which patients might need more aggressive treatment.

While bone marrow tests are still important for diagnosing multiple myeloma, these blood tests (called liquid biopsies) could become a valuable tool. They might help doctors better understand each patient's cancer and choose the best treatment.

 

 

"Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study"

Source

Lee JH, Choi J, Min C-K, Park S-S, Jo J-C, Lee YJ, Kim JS, Eom H-S, Jung J, Moon JH, Cho HJ, Lee M- won, Yoon S-S, Byun JM, Lee JH, Lee J-J, Jung S-H, Shin H-J, Kim DY, Yi JH, Lee S-S, Do YR, Yoon DH, Cho H, Lee WS, Lee HS, Uhm J, Kim HJ, Jang HR, Kim S-H, Kim K. Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study. Haematologica; https://doi.org/10.3324/haematol.2024.285534 [Early view]. June 6, 2024 

Overview

Researchers studied the combination of three drugs: Kyprolis (carfilzomib), Revlimid (lenalidomide), and dexamethasone (KRd) to treat multiple myeloma patients. 

The study looked at 364 patients in Asia who had multiple myeloma that came back after earlier treatment. Here's what they found:

• The treatment worked well for 90% of patients.
• On average, patients lived for about 2 years before their cancer got worse.
• Some factors made the treatment less effective, like certain genetic changes or if the cancer had spread outside the bone marrow.
• Patients who had a stem cell transplant after KRd treatment did better.
• About half of the patients had serious side effects, but only a few had to stop treatment because of them.

Overall, the researchers think KRd is a good option for treating multiple myeloma that has come back after earlier treatments. This information can help doctors decide on the best treatment for their patients.

 

 

"Additional copies of 1q negatively impact the outcome of multiple myeloma patients and induce transcriptomic deregulation in malignant plasma cells"

Source

D’Agostino, M., Rota-Scalabrini, D., Belotti, A. et al. Additional copies of 1q negatively impact the outcome of multiple myeloma patients and induce transcriptomic deregulation in malignant plasma cells. Blood Cancer J. 14, 94 (2024). https://doi.org/10.1038/s41408-024-01075-x June 7, 2024 

Overview

Some people with multiple myeloma have extra copies of part of chromosome 1. This can predict high-risk disease.

Researchers looked at how these extra copies affect patients. They studied 400 people with myeloma who were in a clinical trial. They found:

• 13% had 4 or more copies (called amplification).
• 32% had 3 copies (called gain).
• The rest had the normal 2 copies.

After about 5 years, they checked how patients were doing:

• Those with normal copies did best.
• Those with 3 copies did worse.
• Those with 4 or more copies did the worst.

People with 4 or more copies often got sick again within 2 years. This was even faster if they had other risk factors.

A certain treatment helped people with 3 copies, but not those with 4 or more.

The researchers also looked at how the extra copies change how genes work. They found changes in how cells die, how they respond to stress, and how they grow.

This study helps doctors understand how extra copies of chromosome 1 affect multiple myeloma patients. It may help them choose better treatments in the future.

 

 

"Anthropometric traits and risk of multiple myeloma: differences by race, sex and diagnostic clinical features"

Source

Arnold, K.D., Ong, K.L., Ravi, G. et al. Anthropometric traits and risk of multiple myeloma: differences by race, sex and diagnostic clinical features. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02723-6 June 7, 2024  

Overview

This study examines obesity and multiple myeloma. Here are its key points:

• The study looked at how being overweight affects the risk of getting multiple myeloma.
• Researchers found that for every 5-point increase in BMI (a measure of body fat), the risk of multiple myeloma went up by 18%.
• People with severe obesity (very overweight) had the highest risk of getting multiple myeloma. This was especially true for Black men.
• Overweight or obese people with multiple myeloma were more likely to have certain health problems when diagnosed, such as kidney issues and bone damage.
• The study shows that obesity is an important risk factor for multiple myeloma, especially in high-risk groups like Black men.
• The findings suggest that maintaining a healthy weight could help reduce the risk of multiple myeloma and its complications.

 

 

"Functional multi-omics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma"

Source

Priya Choudhry, Corynn Kasap, Bonell Patiño-Escobar, Olivia Gugliemini, Huimin Geng, Vishesh Sarin, Amrik Kang, Audrey Kishishita, Sham Rampersaud, Letitia Sarah, Yu-Hsiu T. Lin, Neha Paranjape, Poornima Ramkumar, Jonathan C. Patton, Makeba Marcoulis, Donghui Wang, Paul Phojanakong, Veronica Steri, Byron Hann, Benjamin G. Barwick, Martin Kampmann, Arun P. Wiita; Functional multi-omics reveals genetic and pharmacologic regulation of surface CD38 in multiple myeloma. Blood Neoplasia 2024; 100025. doi: https://doi.org/10.1016/j.bneo.2024.100025  June 10, 2024 

Overview

Scientists are studying a protein called CD38 that's found on the surface of cancer cells in multiple myeloma. Darzalex (daratumumab) and Sarclisa (isatuximab) target CD38 to fight the cancer. The more CD38 there is on the cancer cells, the better these drugs work.

Researchers are looking for ways to increase CD38 on cancer cells to make the drugs more effective. They used different methods to study how CD38 is controlled in the body and how it affects cancer cells.

They found the following:

• Certain genes control how much CD38 is made.
• Removing CD38 doesn't change other proteins on the cell surface much.
• Some drugs can increase CD38 levels without affecting many other things.
• The cancer-fighting drugs might work by blocking certain cell signals.

This research helps scientists understand CD38 better and could lead to improved treatments for multiple myeloma.

 

 

"Venetoclax resistance leads to broad resistance to standard-of-care anti-MM agents, but not to immunotherapies"

Source

Anderson, Mariateresa Fulciniti, Nikhil C. Munshi; Venetoclax resistance leads to broad resistance to standard-of-care anti-MM agents, but not to immunotherapies. Blood Adv 2024; bloodadvances.2023012298. doi: https://doi.org/10.1182/bloodadvances.2023012298 June 11, 2024 

Overview

Venetoclax, a fairly new drug, works well for some people with multiple myeloma. It's most effective for patients whose cancer cells have the t(11;14) translocation. While venetoclax helps many patients, some eventually stop responding to it.

Scientists wanted to understand why this happens. They created cancer cells in the lab that became resistant to venetoclax. Then they studied these cells to see what had changed.

They found that the resistant cells had different amounts of certain proteins. These changes made the cells harder to kill with venetoclax and other common myeloma treatments.

However, the resistant cells could still be attacked by treatments that use the body's immune system. This suggests that after venetoclax stops working, doctors might want to try immunotherapy next.

This research helps us understand how cancer cells adapt to survive treatment. It also gives ideas for how to treat patients whose cancer has become resistant to venetoclax.

 

 

"CAR T cell Toxicities: Bedside to Bench - How Novel Toxicities Inform Laboratory Investigations"

Source

Fabiana Perna, Samir Parekh, Caroline Diorio, Melody Smith, Marion Subklewe, Rakesh Mehta, Frederick L Locke, Nirali N Shah; CAR T cell Toxicities: Bedside to Bench - How Novel Toxicities Inform Laboratory Investigations. Blood Adv 2024; bloodadvances.2024013044. doi: https://doi.org/10.1182/bloodadvances.2024013044 June 11, 2024 

Overview

While CAR T-cell therapy shows promise in the treatment of myeloma, it can cause side effects that doctors are still learning about. The most common side effects are well-known, but as more patients receive this treatment, new and complex problems are being discovered.

To better understand these new side effects, the researchers of this study discussed those potential side effects. 

• Movement problems after treating a specific type of cancer
• Blood clotting issues
• Low blood cell counts that last a long time

The researchers also discussed how the body's immune system and gut bacteria might play a role in these side effects. They agreed that more research is needed to understand why these problems happen and how to prevent them.

The group decided it was important to create a system to track these new side effects. This will help doctors learn how to manage these side effects better in the real world.

While CAR T-cell therapy is helpful for some cancers, doctors are working hard to understand and manage its side effects to make the treatment safer for patients.

 

 

"Performance of newer myeloma staging systems in a contemporary, large patient cohort"

Source

Mohyuddin, G.R., Rubinstein, S.M., Kumar, S. et al. Performance of newer myeloma staging systems in a contemporary, large patient cohort. Blood Cancer J. 14, 95 (2024). https://doi.org/10.1038/s41408-024-01076-w June 11, 2024 

Overview

Doctors use different ways to stage multiple myeloma. The most common method is called R-ISS, but it doesn't consider all the important factors. Two new methods, called MASS and R2-ISS, have been suggested. These new methods look at more details about the patient's condition.

Researchers wanted to see how well these new methods work compared to the old one. They looked at information from almost 500 patients with multiple myeloma in the United States. They checked how long patients survived with each method.

Here's what they found:

•  The old method (R-ISS) put most patients in the middle group, but their outcomes varied a lot.
•  The new MASS method spread patients more evenly across three groups. It did a good job of showing differences in how long patients lived.
• The other new method (R2-ISS) divided patients into four groups. However, some of these groups had similar results.

Overall, the new methods seem to do a better job of predicting how patients will do. This could help doctors make better treatment plans for people with multiple myeloma.

 

 

"Mechanisms of resistance to bispecific T-cell engagers in multiple myeloma and their clinical implications"

Source

Eric Letouzé, Philippe Moreau, Nikhil Munshi, Mehmet Samur, Stéphane Minvielle, Cyrille Touzeau; Mechanisms of resistance to bispecific T-cell engagers in multiple myeloma and their clinical implications. Blood Adv 2024; 8 (11): 2952–2959. doi: https://doi.org/10.1182/bloodadvances.2023012354  June 11, 2024 

Overview

Bispecific T-cell engagers (TCEs) are changing how doctors treat multiple myeloma. TCEs are special antibodies that help the body's immune cells fight cancer cells. They work well for some patients whose cancer didn't respond to other treatments.

However, these treatments don't work for everyone. About one-third of patients don't respond at all, and even those who do respond often see their cancer come back later. Scientists are trying to understand why this happens.

There are two main reasons why TCEs might not work:

1. The cancer cells themselves change. They might lose the specific targets that the TCEs are looking for, or they might hide from the immune system in other ways.
2. The patient's immune system gets tired or is blocked by other factors in the body.

Interestingly, sometimes a patient's cancer might resist one type of TCE but still respond to a different one.

To make these treatments work better, doctors may need to check both the cancer cells and the patient's immune system before choosing which TCE to use. They might also combine TCEs with other treatments to improve results.

Understanding why TCEs sometimes fail is helping researchers develop better ways to use these powerful new tools in the fight against multiple myeloma.

 

 

"Beyond BCMA: newer immune targets in myeloma"

Source

Melinda SY Tan, Yunxin Chen, Eric L Smith; Beyond BCMA: newer immune targets in myeloma. Blood Adv 2024; bloodadvances.2023010856. doi: https://doi.org/10.1182/bloodadvances.2023010856 June 12, 2024 

Overview

New treatments for myeloma work by targeting a specific part of cancer cells called BCMA. Today, special drugs are used, and modified immune cells attack the cancer.

These new treatments have helped patients live longer, especially those whose myeloma relapsed after other treatments. Doctors are now trying these treatments earlier in the disease.

However, the myeloma often relapses even after these new treatments. So, scientists are looking for more targets on cancer cells to attack. Some new targets they're studying are called GPRC5D, FcRH5, and SLAMF7.

Having more treatment options is important because it gives doctors more ways to help patients when one treatment stops working. Scientists are also trying to use these treatments one after another or combine them. This might let patients avoid traditional chemotherapy.

To make these treatments work best, doctors need to think carefully about when to use them and how to keep the patient's immune system strong. They also need to understand how the cancer might change/adapt to avoid treatment.

This research is helping doctors find better ways to treat multiple myeloma and give patients more options for fighting their cancer.

 

 

"Anti-BCMA-engineered Exosomes for Bortezomib Targeted Delivery in Multiple Myeloma"

Source

Shushu Yuan, Qi Li, Chuan He, Mengli Bing, Xinyun Zhang, Hao Xu, Zhiming Wang, Meifang Zhao, Yuchen Zhang, Yali Chai, Bingzong Li, Wenzhuo Zhuang; Anti-BCMA-engineered Exosomes for Bortezomib Targeted Delivery in Multiple Myeloma. Blood Adv 2024; bloodadvances.2023012464. doi: https://doi.org/10.1182/bloodadvances.2023012464  June 13, 2024 

Overview

Scientists have found a new way to deliver medicine to cancer cells. They used tiny bubbles called exosomes that come from immune cells in our blood. These exosomes can carry drugs directly to cancer cells without hurting healthy cells.

The researchers focused on a type of cancer called multiple myeloma. They changed the exosomes to stick to a special marker on myeloma cells. Then, they put a cancer drug called Bortezomib inside these modified exosomes.

This new method worked better than just using the drug alone. It killed more cancer cells in lab tests and in mice with myeloma. The drug also stayed in the cancer cells longer, which could make it work better.

Importantly, this method didn't seem to harm normal cells or organs in the mice. It might even help bone cells grow and boost the immune system.

This research shows that using modified exosomes to deliver cancer drugs could be a promising new treatment for multiple myeloma. It might work for other types of cancer too.

 

 

"Patterns of CRS with teclistamab in relapsed/refractory multiple myeloma with or without prior T-cell redirection therapy"

Source

Issam S. Hamadeh, Tala Shekarkhand, Colin Rueda, Ross S. Firestone, Alice X. Wang, Neha Korde, Malin L. Hultcrantz, Alexander M. Lesokhin, Sham Mailankody, Hani Hassoun, Urvi A. Shah, Kylee Maclachlan, Sridevi Rajeeve, Dhwani Patel, Gunjan L. Shah, Michael Scordo, Oscar B. Lahoud, David J. Chung, Heather J. Landau, Sergio Giralt, Saad Z. Usmani, Carlyn R. Tan; Patterns of CRS with teclistamab in relapsed/refractory multiple myeloma with or without prior T-cell redirection therapy. Blood Adv 2024; 8 (12): 3038–3044. doi: https://doi.org/10.1182/bloodadvances.2024012724  June 25, 2024 

Overview

Scientists studied a new cancer drug called Teclistamab (Tec) that helps treat multiple myeloma, a type of blood cancer. They wanted to see if patients who had used similar drugs before had fewer side effects when taking Tec.

The main side effect they looked at is called cytokine release syndrome (CRS). It can happen when the immune system reacts strongly to the drug.

The researchers looked at 72 patients who took Tec. They split them into two groups:

1. Those who had used similar drugs before
2. Those who had never used similar drugs

They found that:

• Only 37% of patients who had used similar drugs before got CRS
• 80% of patients who had never used similar drugs got CRS

This means that patients who had used similar drugs before were less likely to get CRS when taking Tec. In fact, patients who had never used similar drugs were about four times more likely to get CRS.

This information is important because it can help doctors better prepare for and prevent side effects in patients taking Tec. It might also help them decide which patients might benefit most from this drug.

 

 

"Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity"

Source

Zhang, JN., Dong, MM., Cao, W. et al. Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02742-3 June 14, 2024 

Overview

Scientists are looking for new ways to treat multiple myeloma (MM). They're focusing on a part of our cells called DNA-PKcs, which helps repair damaged DNA.

The researchers found that blocking DNA-PKcs makes cancer cells more sensitive to a chemotherapy drug called doxorubicin. This happens because of a chain reaction in the cells:

• When DNA-PKcs is blocked and doxorubicin damages the DNA, pieces of DNA end up in the wrong part of the cell.
• These misplaced DNA pieces activate a system in the cell called cGAS-STING.
• The cGAS-STING system then triggers two important effects:
  • It causes cancer cells to die.
  • It helps nearby immune cells become better at fighting cancer.

The scientists discovered that blocking DNA-PKcs doesn't just stop DNA repair. It also helps release a protein called cGAS from damaged DNA, which is crucial for activating the cGAS-STING system.

This research suggests that combining drugs that block DNA-PKcs with Doxil (doxorubicin) could be a more effective way to treat multiple myeloma. It works by making the cancer cells more vulnerable and boosting the body's immune response against the cancer.

 

 

"Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity"

Source

Zhang, JN., Dong, MM., Cao, W. et al. Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02742-3 June 14, 2024 

Overview

Scientists are looking for new ways to treat multiple myeloma (MM). They're focusing on a part of our cells called DNA-PKcs, which helps repair damaged DNA.

The researchers found that blocking DNA-PKcs makes cancer cells more sensitive to a chemotherapy drug called doxorubicin. This happens because of a chain reaction in the cells:

• When DNA-PKcs is blocked and doxorubicin damages the DNA, pieces of DNA end up in the wrong part of the cell.
• These misplaced DNA pieces activate a system in the cell called cGAS-STING.
• The cGAS-STING system then triggers two important effects:
  • It causes cancer cells to die.
  • It helps nearby immune cells become better at fighting cancer.

The scientists discovered that blocking DNA-PKcs doesn't just stop DNA repair. It also helps release a protein called cGAS from damaged DNA, which is crucial for activating the cGAS-STING system.

This research suggests that combining drugs that block DNA-PKcs with Doxil (doxorubicin) could be a more effective way to treat multiple myeloma. It works by making the cancer cells more vulnerable and boosting the body's immune response against the cancer.

 

 

"NK cells with adhesion defects and reduced cytotoxic functions are associated with a poor prognosis in Multiple Myeloma"

Source

Eve Blanquart, Rüçhan Ekren, Bineta Rigaud, Marie Veronique Joubert, virginie Baylot, Hélène Daunes, Marine Cuisinier, Marine Villard, Nadège Carrié, Celine Mazzotti, Liliana E Lucca, Aurore Perrot, Jill Corre, Thierry Walzer, Hervé Avet-Loiseau, Pierre-Paul Axisa, Ludovic Martinet; NK cells with adhesion defects and reduced cytotoxic functions are associated with a poor prognosis in Multiple Myeloma.. Blood 2024; blood.2023023529. doi: https://doi.org/10.1182/blood.2023023529  June 14, 2024 

Overview

Researchers want to use the body's own immune system to fight multiple myeloma. This study focused on Natural Killer (NK) cells, which are important for attacking cancer cells.
The researchers looked at NK cells from 10 people with multiple myeloma and 10 healthy people. They found that patients with multiple myeloma had different types of NK cells than healthy people. These NK cells were less able to fight myeloma and showed signs of inflammation.

The study also looked at 177 multiple myeloma patients. They found that having more of these less effective NK cells was linked to shorter survival times.

This research helps us understand why some patients' immune systems don't fight multiple myeloma well. It could lead to new treatments that make NK cells better at fighting myeloma.

 

 

"Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma"

Source

Naresh Bumma et al., Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma. JCO 0, JCO.24.01008 DOI:10.1200/JCO.24.01008 June 16, 2024.  

Overview

Scientists tested a new medicine called linvoseltamab for people with multiple myeloma. The patients' myeloma had come back or didn't respond to other treatments. They wanted to see if the medicine was safe and if it worked.

The study looked at two doses: 50 mg and 200 mg. People got the medicine once a week for 14 weeks, then every two weeks. Some people who did well on the 200 mg dose got it every four weeks later on.

Out of 117 people who got the 200 mg dose:

• 71% of patients had their cancer respond to the treatment
• 50% had a very good response or better

For the 50 mg dose, 48% of patients responded, with 21% having a very good response or better.

The 200 mg dose worked for about 29.4 months on average. The most common side effects were:

• A reaction called cytokine release syndrome
• Low white blood cell count
• Low red blood cell count
• Infections

Some people also had brain-related side effects.

The scientists concluded that the 200 mg dose of linvoseltamab worked well and lasted a long time for many patients. They thought the side effects were acceptable for a cancer treatment.

 

 

"Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial"

Source

Prof Philippe Moreau, MD, Cyrille Hulin, MD, Aurore Perrot, MD, Bertrand Arnulf, MD, Karim Belhadj, MD, Lotfi Benboubker, MD et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial. The Lancet Oncology. Published:June 15, 2024. 

Overview

Scientists did a long-term study called CASSIOPEIA to test a new treatment for people newly diagnosed with multiple myeloma. The study had two parts and looked at patients who could have stem cell transplants.

In the first part, they compared two treatments:

1. A combination of drugs including daratumumab (D-VTd)
2. The same combination without daratumumab (VTd)

They gave these treatments before and after stem cell transplants. The D-VTd group had better results.

In the second part, they tested if giving daratumumab alone as a maintenance treatment was better than no maintenance treatment. They found that:

1. Patients who got daratumumab maintenance went longer without their cancer getting worse.
2. This was true whether they had D-VTd or VTd in the first part.

After about 6.5 years of following patients, the researchers concluded that:

1. Using daratumumab in both parts of treatment (before/after transplant and as maintenance) gave the best results.
2. D-VTd should be considered a standard treatment for newly diagnosed myeloma patients who can have transplants.
3. Daratumumab alone is a good option for maintenance treatment after transplant.

This study helps doctors know how to better treat people newly diagnosed with multiple myeloma who can have stem cell transplants.

 

 

"Outpatient Administration of CAR T-cell Therapies Using a Strategy of No Remote Monitoring and Early CRS Intervention"

Source

Fateeha Furqan, Vineel Bhatlapenumarthi, Binod Dhakal, Timothy S. Fenske, Faiqa Farrukh, Walter Longo, Othman Salim Akhtar, Anita D'Souza, Marcelo C Pasquini, Guru Subramanian Guru Murthy, Lyndsey Runaas, Sameem Abedin, Meera Mohan, Nirav N. Shah, Mehdi Hamadani; Outpatient Administration of CAR T-cell Therapies Using a Strategy of No Remote Monitoring and Early CRS Intervention. Blood Adv 2024; bloodadvances.2024013239. doi: https://doi.org/10.1182/bloodadvances.2024013239 June 18, 2024 

Overview

CAR T-cell therapy is a new cancer treatment that changes a patient's immune cells to fight cancer. Doctors are trying to give this treatment to patients without keeping them in the hospital. This study looked at how well that worked.

The study included 58 patients with blood cancers who got CAR T-cell therapy as outpatients in 2022-2023. Patients came to the cancer center daily for 7-10 days after treatment, then twice a week for up to 30 days.

The main goal was to see how many patients needed to go to the hospital within 3, 7, and 30 days after treatment. Doctors also tried to treat side effects early to keep patients out of the hospital.

Results showed:

• 41% of patients went to the hospital in the first 3 days
• 38% went to the hospital between days 4-7
• 21% went to the hospital between days 8-30

The most common reason for going to the hospital was treatment side effects. Early treatment of side effects helped 15 out of 35 patients avoid the hospital.

Very few patients died from causes not related to their cancer: 1.7% after 1 month and 3.4% after 6 months.

The study concluded that giving CAR T-cell therapy to outpatients can be safe and doable without constant monitoring at home. Treating side effects early helped make this possible.

 

 

"The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer"

Source

Yan, P., Lin, X., Wu, L. et al. The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer. Nat Commun 15, 5255 (2024). https://doi.org/10.1038/s41467-024-49625-y June 19, 2024 

Overview

GPRC5D is a special protein found on the surface of multiple myeloma cancer cells. Doctors are interested in GPRC5D because it could be a good target for new cancer treatments.

Scientists have been working on different ways to attack GPRC5D, like using antibodies or special immune cells. But they didn't know enough about how GPRC5D is built or how antibodies stick to it. This made it hard to create good treatments.

In this study, scientists looked closely at the structure of GPRC5D. They used a special antibody to help them see it better. Here's what they found:

• GPRC5D looks similar to other proteins in its family, especially in the part that goes through the cell membrane.
• GPRC5D forms pairs with itself in a unique way. This is different from how other similar proteins pair up.
• They found where the antibody sticks to GPRC5D. This is important for making new treatments.

These findings help scientists understand GPRC5D better. This could lead to better treatments for multiple myeloma in the future.

 

 

"Unscheduled health care interactions in patients with multiple myeloma receiving T-cell redirection therapies"

Source

Anna J. Howard, Isabel Concepcion, Alice X. Wang, Issam S. Hamadeh, Malin Hultcrantz, Sham Mailankody, Carlyn Tan, Neha Korde, Alexander M. Lesokhin, Hani Hassoun, Urvi A. Shah, Kylee H. Maclachlan, Sridevi Rajeeve, Heather J. Landau, Michael Scordo, Gunjan L. Shah, Oscar B. Lahoud, David J. Chung, Sergio Giralt, Saad Z. Usmani, Ross S. Firestone; Unscheduled health care interactions in patients with multiple myeloma receiving T-cell redirection therapies. Blood Adv 2024; 8 (12): 3246–3253. doi: https://doi.org/10.1182/bloodadvances.2024012871 June 25, 2024  

Overview

New treatments like CAR T-cell therapy and bispecific antibody (BsAb) therapy are helping patients with relapsed/refractory multiple myeloma (RRMM) live longer.

This study looked at how often patients with RRMM who were doing well on these new treatments needed unexpected medical care. The researchers called these "unscheduled health care interactions" or UHIs. UHIs included things like calling the doctor's office, sending messages online, or going to urgent care.

The study found:

1. Almost all patients (89%) needed some kind of UHI in the first 125 days of treatment.
2. On average, each patient had 3.7 UHIs.
3. Patients on BsAb therapy were more likely to contact their doctors or visit urgent care than those on CAR T-cell therapy.
4. BsAb patients often had mild colds or flu-like symptoms.

The researchers think it's important to plan ahead for common symptoms patients might have during these treatments. This could help reduce unnecessary medical visits and improve patients' quality of life.

In conclusion, while these new treatments are helping patients with RRMM, they still often need extra medical care. Planning ahead for common issues could make things easier for patients.

 

 

"CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma"

Source

Ismael, A., Robinette, A.J., Huric, L. et al. CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma. Leukemia (2024). https://doi.org/10.1038/s41375-024-02303-w June 20, 2024   

Overview

Researchers have found that a molecule called HLA-E helps multiple myelom (MM) cells hide from the immune system. 

In patients with MM, higher levels of HLA-E are linked to more aggressive cancer. The tumor environment can cause MM cells to make more HLA-E.

The researchers discovered that a protein called CREB1 controls how much HLA-E is made. When they blocked CREB1, it reduced HLA-E levels in MM cells.

HLA-E works by stopping natural killer (NK) cells, which are part of the immune system, from attacking cancer cells. When the researchers used a drug to block CREB1, it allowed NK cells to better kill MM cells in lab tests.

This research shows that blocking CREB1 could be a new way to help the immune system fight multiple myeloma more effectively.

 

 

"Loss of GABARAP mediates resistance to immunogenic chemotherapy in multiple myeloma"

Source

Annamaria Gulla, Eugenio Morelli, Megan Johnstone, Marcello Turi, Mehmet K. Samur, Cirino Botta, Selma Cifric, Pietro Folino, Delaney Vinaixa, Francesca Barello, Cole Clericuzio, Vanessa Katia Favasuli, Domenico Maisano, Srikanth Talluri, Rao Prabhala, Giada Bianchi, Mariateresa Fulciniti, Kenneth Wen, Keiji Kurata, Jiye Liu, Johany Penailillo, Alberto Bragoni, Anna Sapino, Paul G. Richardson, Dharminder Chauhan, Ruben D. Carrasco, Teru Hideshima, Nikhil C. Munshi, Kenneth C. Anderson; Loss of GABARAP mediates resistance to immunogenic chemotherapy in multiple myeloma. Blood 2024; 143 (25): 2612–2626. doi: https://doi.org/10.1182/blood.2023022777 June 20, 2024   

Overview

Researchers have found a way to make cancer treatments work better by triggering the body's immune system to fight cancer cells. This method is called immunogenic cell death (ICD).

In multiple myeloma, Velcade (bortezomib) can cause ICD. However, over time, the cancer can become resistant to this treatment.

Scientists discovered that a protein called GABARAP plays a crucial role in making cancer cell death visible to the immune system. When GABARAP is missing, the treatment doesn't work as well.

Some multiple myeloma patients have a higher risk because they're missing part of a chromosome that contains the GABARAP gene. These patients often have shorter survival times and less immune cell activity in their tumors.

The researchers found that GABARAP helps move another important protein, calreticulin, to the surface of dying cancer cells. This process tells the immune system to attack the cancer.

When GABARAP is missing, this doesn't happen as well. But the scientists found a solution: using a drug called rapamycin alongside bortezomib can help fix this problem.

This discovery could lead to better treatments for multiple myeloma patients, especially those with high-risk forms of the disease.

 

 

"Multiple myeloma incidence and mortality trends in the United States, 1999–2020"

Source

Zhu, D.T., Park, A., Lai, A. et al. Multiple myeloma incidence and mortality trends in the United States, 1999–2020. Sci Rep 14, 14564 (2024). https://doi.org/10.1038/s41598-024-65590-4  June 24, 2024   

Overview

Researchers wanted to understand how multiple myeloma (MM) has changed over time in the United States and if it affects some groups more than others.

They looked at information about MM from 1999 to 2020. They found that more people are getting MM, but fewer people are dying from it. However, the disease doesn't affect everyone equally.

Black people who are not Hispanic have the highest rates of getting MM, and these rates keep going up. On the other hand, American Indians, Native Alaskans, Asians, and Pacific Islanders have the lowest rates.

The study also found differences based on gender, age, where people live in the US, and whether they live in cities or rural areas. These findings show that we need to focus on helping the groups most at risk of getting MM. This might include special programs to check for MM in these groups early on.

 

 

"The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities"

Source

Ramberger, E., Sapozhnikova, V., Ng, Y.L.D. et al. The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities. Nat Cancer (2024). https://doi.org/10.1038/s43018-024-00784-3 June 28, 2024. 

Overview

Even with new treatments, multiple myeloma is still incurable. Doctors need better ways to predict how the disease will progress and develop new therapies.

Scientists studied the proteins in MM cells for the first time. They looked at the proteins, genes, and other parts of the cells from 138 patients with different stages of the disease. They also examined healthy cells for comparison.

The researchers found that:

• MM cells have very different proteins compared to healthy cells.
• These protein differences are caused by changes in chromosomes and how genes are used.
• They identified a group of proteins that can help predict if the disease will be more aggressive.
• They discovered new potential targets for treatments, including some that might work for specific genetic types of MM.

This study shows how looking at proteins can help us understand cancer better. It also provides a resource for other scientists to use in finding new ways to treat MM.