A summary of some notable key multiple myeloma research from December 2025 to January 2026

Scope and Methodology  
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from December 2025 - January 2026. Content was developed by the International Myeloma Foundation medical editorial team using various medical abstracts on new guidelines, recommendations, reviews, letters to the editor, correspondence, and the latest results of ongoing clinical trials. It is intended for patients, care partners, and oncology professionals. This blog article was medically reviewed by Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, on January 28, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.  
 

At the end of each month, the International Myeloma Foundation (IMF) brings you some of the latest and most relevant news (myeloma research, clinical trials, treatments, drug authorizations, and more) to give a renewed sense of hope, courage, and resilience to the myeloma community.     
 

Guidelines/Recommendations 

European Expert Recommendations on Teclistamab Management for Relapsed or Refractory Multiple Myeloma — Clinical Lymphoma Myeloma and Leukemia (December 2025) 
 

Background  

Multiple myeloma (MM) is a blood cancer that often relapses, even after treatment. When the disease has already been treated with the three main types of therapy and still returns, outcomes are usually poor. New immune-based treatments are improving options for these patients. 
 
What is teclistamab (Tecvayli®)?  

Teclistamab (Tecvayli®) is a bispecific antibody that helps the body’s own immune cells recognize and kill myeloma cells. It targets a marker called B-cell maturation antigen (BCMA) — a protein expressed on myeloma cells. Teclistamab is an “off-the-shelf” treatment, meaning it does not require complex cell collection like CAR-T therapy. 
 
How well does it work? 
    • In clinical trials and real-world use, about 6 out of 10 patients respond to teclistamab. 
    • Many responses are deep and long-lasting, especially when the disease responds strongly. 
    • It works not only in younger or fitter patients, but also in older adults, frail patients, and those with kidney problems. 
    • Results from everyday clinical practice largely confirm the benefits seen in trials. 
 
Who can receive it?  

European guidelines now recommend teclistamab from the second relapse onward for patients whose myeloma has already been treated with the three main drug classes. 
 
What are the main side effects?  

The most common side effects are: 
    • Infections 
    • Low blood counts 
    • Cytokine release syndrome (CRS), an inflammatory reaction that usually happens early and is often manageable 
 

Importantly, only a small number of patients need to stop treatment because of side effects. 
 
How are side effects best managed?  

Experts emphasize that good supportive care is essential: 
    • Start infection prevention measures early 
    • Use immunoglobulin replacement therapy (IgRT) from the start to lower infection risk 
    • Closely monitor patients, especially at the beginning of treatment 
    • For patients who respond well, switching to every-other-week dosing can reduce serious infections 
 
Why is this guidance important?  

Because teclistamab is still relatively new, clear practical recommendations help doctors use it safely and effectively in real-world patients, including those not well represented in clinical trials. 
 
Bottom line  

Teclistamab is an effective and generally manageable treatment for difficult-to-treat multiple myeloma. With careful patient selection, early infection prevention, and ongoing monitoring, it can significantly improve outcomes for many patients. 
 
Reference: 
Paula Rodríguez-Otero, Philippe Moreau, Maria Victoria Mateos, Maria Theresa Krauth, Leo Rasche, Efstathios Kastritis, Albert Oriol, Elena Zamagni, Claire Albrecht, Eva Rubio Azpeitia, Niels W.C.J. van de Donk, European Expert Recommendations on Teclistamab Management for Relapsed or Refractory Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia,  2025,ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.003 (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)04298-3/fulltext).   

Bispecific Antibody Therapy for Multiple Myeloma: A Practical Toolkit — Clinical Lymphoma Myeloma and Leukemia (December 2025) 
 

Background 
Bispecific antibodies are a newer type of immune therapy for people with multiple myeloma whose disease has come back or no longer responds to standard treatments. These medicines work by helping the patient’s own T cells recognize and attack myeloma cells. Unlike CAR-T cell therapy, bispecific antibodies are “off-the-shelf,” meaning they do not need to be custom-made for each patient. 
 
What is the purpose of this review? 
Experts from the United States, Europe, and Latin America reviewed their real-world experience to share practical advice on how to safely give these treatments and manage patients over time. 

Key points  
    • Bispecific antibodies that target BCMA or GPRC5D are effective treatment options for many patients with relapsed or refractory multiple myeloma, sometimes as early as the third line of therapy. 
    • Treatment usually starts in the hospital. Patients receive preventive medications and gradually increasing “step-up” doses to reduce side effects. 
    • During treatment, patients need close monitoring, especially for infections and other known side effects. 
    • Educating patients and caregivers about possible side effects and medications helps doctors tailor care and manage problems early. 
    • In long-term treatment, bispecific antibodies may need to be temporarily paused if side effects occur and are being evaluated. 

Why this review is important 
Overall, clinical trials and real-world experience show that bispecific antibodies can lead to meaningful and sometimes deep responses in heavily treated patients, with side effects that can usually be managed. The goal of this expert guidance is to help healthcare teams use these therapies safely and effectively, improving outcomes for people living with multiple myeloma. 
 
Reference: 
Cesar Rodriguez, Cyrille Touzeau, Edvan de Queiroz Crusoe, Fernando Vieira Pericole, Vania Hungria, Bispecific Antibody Therapy for Multiple Myeloma: A Practical Toolkit, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.015 (https://www.sciencedirect.com/science/article/abs/pii/S215226502504323X).  
 
 

Treatment of Multiple Myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline — Journal of Clinical Oncology (January 2026) 

Background 
This update provides the latest expert guidance on how multiple myeloma should be treated, based on a large review of clinical trial evidence. 
 
How the guidance was developed 
Cancer experts from ASCO and Ontario Health reviewed results from 161 high-quality clinical trials to determine the most effective treatment approaches. 
 

Key treatment recommendations 
    • High-risk smoldering multiple myeloma (early disease with higher risk of progression): Treatment with daratumumab may be offered to delay or prevent progression. 
    • Newly diagnosed patients who are eligible for stem cell transplant: Doctors should use a four-drug combination that includes: 
      - Daratumumab or isatuximab 
      - Bortezomib 
      - Lenalidomide 
      - Dexamethasone 

After initial treatment and transplant, patients should receive maintenance therapy, at minimum lenalidomide, with or without additional drugs such as daratumumab or carfilzomib. 
    • Newly diagnosed patients who are not eligible for transplant: Similar four-drug combination therapy should be offered when appropriate. 
    • Relapsed or refractory multiple myeloma: Patients should receive three-drug combinations or newer T-cell–based immunotherapies, chosen based on prior treatments and overall health. 

What this means for patients 
This updated guideline emphasizes earlier and stronger combination treatments, especially those including modern antibody therapies, to improve outcomes across all stages of multiple myeloma. For more details, patients and caregivers can visit the ASCO guideline website on blood cancers. 
 
Reference: 
Lisa K. Hicks et al. Treatment of Multiple Myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline. J Clin Oncol 0, JCO-25-02587 DOI:10.1200/JCO-25-02587 (https://ascopubs.org/doi/10.1200/JCO-25-02587)  
 

 

High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing — Blood (January 2026) 
 

Background 
Multiple myeloma outcomes vary widely, largely because of differences in the cancer’s genetic features. The International Myeloma Society (IMS) and International Myeloma Working Group (IMWG) recently developed a Consensus Genomic Staging system to better define high-risk (HR) multiple myeloma based on tumor genetics. 
 
What is the purpose of the study? 
In this study, researchers analyzed genetic data using next-generation sequencing from 6,528 patients with newly diagnosed multiple myeloma (NDMM) and 1,583 patients at first relapse treated between 2019 and 2024. Using the IMS/IMWG genomic criteria, 22.4% of patients at diagnosis (excluding the β2-microglobulin criterion) and 36.7% at first relapse were classified as high risk. 
 
Key findings 
Among 2,695 newly diagnosed patients with available clinical data and a median follow-up of 35 months, median progression-free survival (PFS) was 30 months in HR patients compared with 51 months in standard-risk (SR) patients (P < .0001). Traditional high-risk cytogenetic criteria from the Revised International Staging System (R-ISS) did not reliably distinguish HR from SR patients when compared with the genomic classification. 

Specific genetic abnormalities—such as del(17p), TP53 mutation, biallelic del(1p32), or combinations of intermediate-risk cytogenetic changes (gain 1q, del(1p32), t(4;14), t(14;16), t(14;20))—were each associated with shorter PFS. Patients with multiple high-risk genetic features had the poorest outcomes. Among genomically defined SR patients with normal kidney function, a high β2-microglobulin level did not significantly affect PFS. 

Why this study matters

Overall, this large, modern study confirms that the IMS/IMWG genomic definition of high-risk multiple myeloma effectively identifies patients with poorer outcomes and improves risk stratification beyond older staging systems. 
 
Reference: 
Anaïs Schavgoulidze, Aurore Perrot, Xavier Leleu, Titouan Cazaubiel, Marie-Lorraine Chretien, Pierre Feugier, Karim Belhadj, Salomon Manier, Murielle Roussel, Sabine Brechignac, Frédérique Orsini-Piocelle, Mohamad Mohty, Jean-Marc Schiano de Collela, Margaret Macro, Didier Adiko, Mamoun Dib, Jean Fontan, Carine Luttiau-Motard, Didier Bouscary, Laurent Pascal, Virginie Roland, François Lifermann, Jana Bakala, Lydia Montes, Céline 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 2026; 147 (3): 266–275. doi: https://doi.org/10.1182/blood.2025029999   (https://ashpublications.org/blood/article-abstract/147/3/266/547443/High-risk-genomic-consensus-validation-for)
 
 
 

Review 

 
Skeletal health in the precursor stages of multiple myeloma: fracture risk and bone phenotypes in monoclonal gammopathy of undetermined significance and smouldering myeloma — Pathology (December 2025) 
 

Summary 
Multiple myeloma (MM) is a blood cancer that often damages bones, causing pain and fractures. Most people with MM first pass through earlier stages called monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). These early conditions usually have no symptoms and are not treated, and clear bone damage is not seen on scans. 

However, research shows that people with MGUS already have a higher risk of fractures, especially in the spine. This is linked to lower bone density and increased bone breakdown by cells called osteoclasts. These bone changes are subtle and not seen everywhere in the skeleton, but they suggest that bone weakness can begin before myeloma develops. 

People with stable MGUS usually do not show widespread bone damage, yet they still fracture more often, indicating a unique but not fully understood bone condition. In contrast, people with rapidly progressing MGUS or SMM show stronger signs of increased bone breakdown. At this stage, bone formation may still partly balance bone loss, which may explain why obvious bone holes (lytic lesions) are not yet present. 

Currently, there are no standard guidelines for monitoring bone health or using bone-protective treatments in MGUS or SMM. More research is needed to better understand when and how bone damage begins, and to identify the point at which bone loss outweighs bone repair as the disease progresses to MM. 

Why this review matters 
Understanding these early bone changes may help doctors identify patients at higher fracture risk, decide when to monitor bone health more closely, and determine whether early treatment could reduce fractures, improve quality of life, and possibly improve outcomes as MM develops. 
 
Reference: 
Melissa D. Cantley, Laura J. Trainor, Emma A-J. Cheney, Suzanne M. Watt, Kate Vandyke, Skeletal health in the precursor stages of multiple myeloma: fracture risk and bone phenotypes in monoclonal gammopathy of undetermined significance and smouldering myeloma, Pathology, 2025, ISSN 0031-3025, https://doi.org/10.1016/j.pathol.2025.11.002.  (https://www.sciencedirect.com/science/article/pii/S0031302525003484) 

Fifteen years of use of functional imaging in multiple myeloma: where we started and where we are going — Blood Advances (December 2025) 
 

Why imaging matters in myeloma  

Bone damage is a key feature of multiple myeloma and affects most patients at some point. Imaging scans are essential to: 
    • Detect bone damage 
    • Tell active disease from inactive disease 
    • Estimate prognosis (how aggressive the disease is) 
    • Check how well treatment is working 

There are two main types of imaging: 
    • Structural imaging (shows bone damage) 
    • Functional imaging (shows how active the disease is) 
 
Current standard imaging test: PET/CT (18F-FDG–PET/CT) 
    • Combines CT scans (bone structure) with PET scans (cancer activity) 
    • Can detect bone lesions, disease outside the bone marrow, and fractures 
    • Helps doctors predict outcomes and monitor response to treatment 
    • Recommended by international guidelines to assess minimal residual disease (very small amounts of cancer after treatment) 
 
Strengths 
    • Widely available and well standardized 
    • Very useful for prognosis and treatment response 
    • Works even in patients with kidney failure or metal implants 
 
Limitations 
    • About 10% of patients have disease that does not show up well on PET 
    • Inflammation or infections can sometimes look like cancer 
 
Whole-body diffusion-weighted MRI (WB-DW-MRI): A very promising alternative 
    • Measures how water moves inside tissues, which reflects cancer cell density 
    • Does not use radiation or contrast dye 
    • Often detects more bone lesions than PET/CT 
    • Especially sensitive for early disease and bone marrow involvement 
 
Strengths 
    • Excellent for detecting disease spread in the bones 
    • Useful for tracking treatment response 
    • Recommended as an alternative to PET/CT in some national guidelines (e.g. UK) 
 
Limitations 
    • Less widely available 
    • Takes longer to perform 
    • Requires specialized expertise to interpret 
 
Comparing PET/CT and WB-DW-MRI 
    • PET/CT is better standardized and has stronger evidence for predicting outcomes 
    • WB-DW-MRI is often more sensitive for finding bone disease 
    • The two techniques are complementary, and using both can give the most accurate picture 
 
Other imaging techniques 
    • Dynamic contrast-enhanced MRI (DCE-MRI): studies blood flow in bone marrow; useful but not yet standardized 
    • PET/MRI: combines PET and MRI in one scan; very informative but expensive and limited in availability 
 
What guidelines say 
    • PET/CT is currently considered the standard imaging test in multiple myeloma 
    • WB-DW-MRI is increasingly recognized as a strong alternative, especially for monitoring response 
    • New guidelines are being developed and may rely more on functional imaging alone 
 
Looking ahead 
    • Artificial intelligence and advanced software may soon help doctors interpret scans more accurately 
    • Future research will clarify whether one imaging test will become the new standard or whether different scans should be used together 
 
Bottom line  

Imaging is essential in multiple myeloma care. PET/CT is currently the standard test, while whole-body diffusion MRI is a powerful and growing alternative. Together, these scans help doctors diagnose disease, guide treatment decisions, and monitor how well therapies are working. 
 
Reference: 
Elena Zamagni, Marco Talarico; Fifteen years of use of functional imaging in multiple myeloma: where we started and where we are going. Blood Adv 2025; 9 (24): 6252–6266. doi: https://doi.org/10.1182/bloodadvances.2024015686  (https://ashpublications.org/bloodadvances/article/9/24/6252/546994/Fifteen-years-of-use-of-functional-imaging-in)
 

Undetectable Minimal Residual Disease in Multiple Myeloma: Bridging the Gap Between Clinical Trials and Real-life Application, Clinical Lymphoma Myeloma and Leukemia (December 2025) 
 

Background 
Minimal residual disease (MRD) refers to very small numbers of myeloma cells that can remain in the body after treatment, even when standard tests show no signs of cancer. New, highly sensitive tests can now detect these cells at extremely low levels. 
 

Why MRD matters 
    • People with multiple myeloma who achieve undetectable MRD—meaning no cancer cells are found with these sensitive tests—tend to live longer and have better long-term outcomes. 
    • Staying MRD-negative for a sustained period (usually at least 12 months) is especially linked to improved survival. 
    • Because MRD status predicts long-term benefit, the U.S. FDA now accepts undetectable MRD as an early endpoint in clinical trials. This helps speed up approval of new treatments. 
How MRD is measured 
    • Advanced tests such as next-generation flow cytometry (NGF) and next-generation sequencing (NGS) can detect one myeloma cell among up to one million normal cells (10⁻⁶ sensitivity). 
    • These tests give doctors a much clearer picture of how deeply a treatment has worked than standard blood or urine tests. 
 

How MRD may guide treatment 
    •    Ongoing clinical trials are testing MRD-guided strategies to personalize care. 
    •    Depending on MRD results, treatment might be safely stopped, reduced, continued, or intensified. 
    •    Key questions remain about who should be tested, when testing should be done, and how best to use MRD results in everyday care. 
 
In summary 
MRD testing is becoming an important tool in multiple myeloma care. It helps doctors better predict outcomes, evaluate new treatments faster, and may soon allow more personalized treatment plans that balance effectiveness with quality of life. 
 
Reference: 
Roberto Mina, Elisabetta Antonioli, Gregorio Barilà, Niccolò Bolli, Cirino Botta, Anna Furlan, Carmine Liberatore, Marina Martello, Sonia Moré, Stefania Oliva, Bernardo Rossini, Elona Saraci, Antonio Giovanni Solimando, Paola Storti, Elena Zamagni, Undetectable Minimal Residual Disease in Multiple Myeloma: Bridging the Gap Between Clinical Trials and Real-life Application, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.016 (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)04322-8/abstract).  
 

Extramedullary Disease—Achilles Heel in Myeloma? — American Journal of Hematology (December 2025) 
 

Summary 
Extramedullary disease (EMD) is a rare but very aggressive form of multiple myeloma. In EMD, cancerous plasma cells grow outside the bone marrow. The most severe type, called true EMD, occurs when these tumors become completely independent of the bone and bone marrow. Patients with true EMD usually have a much poorer outlook than other people with multiple myeloma. 

EMD develops because myeloma cells lose their normal ability to stick to the bone marrow and instead spread and grow elsewhere in the body. This process involves many complex changes inside the cancer cells, including genetic mutations and differences in how tumor cells interact with their surroundings. Tumors in EMD are often more diverse and behave more like solid cancers, which makes them harder to treat. 

How EMD is defined is very important. Some patients have tumors that extend from the bone (called bone-associated plasmacytomas), and these patients often respond to treatment similarly to typical myeloma patients. In contrast, patients with true EMD are often younger and have much worse outcomes. Unfortunately, many studies have not clearly separated these two groups, making results harder to interpret. 

Modern imaging techniques, especially PET-CT scans and whole-body MRI, are essential for diagnosing and monitoring EMD. These scans help doctors see active disease and measure how well treatment is working. For EMD, imaging is just as important as blood tests, and new standards are being developed to better assess response to treatment. 

Until recently, treatment results for EMD—especially in patients whose disease has come back or stopped responding—were poor. Traditional therapies often worked in fewer than 25% of patients. New immunotherapies, such as CAR-T cells and bispecific antibodies, have improved outcomes, but patients with true EMD still respond less well than those without EMD. 

Encouragingly, newer approaches that target more than one cancer marker at the same time have shown promising results. In one recent study, nearly 80% of patients with true EMD responded to a dual-target immunotherapy, with many responses lasting over a year. 

Because EMD progresses quickly and can be life-threatening, fast and widely available treatments are especially important. As therapies continue to improve, more clinical studies focused specifically on patients with true EMD are urgently needed to improve outcomes. 

Reference: 
S. Kumar, J. Richter, S. Z. Usmani, et al., “Extramedullary Disease—Achilles Heel in Myeloma?” American Journal of Hematology (2025): 1–16, https://doi.org/10.1002/ajh.70138. (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70138)  

 

Inconsistent definitions of transplant ineligibility in multiple myeloma: A systematic review — British Journal of Haematology (January 2026) 

What is the purpose of this review? 
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard treatment for many people newly diagnosed with multiple myeloma. However, some patients are considered “transplant ineligible,” often because of age, other health problems, or overall fitness. This review looked at how clinical trials define transplant ineligibility—and found that the definitions are often unclear and inconsistent. 
 
Summary 
Researchers reviewed 55 randomized clinical trials of patients with newly diagnosed multiple myeloma who did not receive ASCT. Fewer than half of these studies clearly explained why patients were considered ineligible for transplant. Many trials relied mainly on age cut-offs, most commonly age 65 or older, sometimes without considering overall health or frailty. Very few studies clearly listed which medical conditions made patients ineligible, and only about one in five used formal tools to measure frailty. 

Over time, the average age of patients in these trials increased, suggesting growing comfort with treating older adults. Despite being labeled “transplant ineligible,” most patients in these studies were relatively fit, had good physical functioning, and were not frail. Patients with poor health or significant frailty were often excluded from trials altogether. 

Recent studies show that some patients can do very well without transplant, especially with newer drug combinations, but long-term outcomes are still being studied. Importantly, transplant-related death rates are very low, even in carefully selected patients over age 75, showing that age alone does not reliably predict transplant risk or benefit. 

Overall, this review highlights that transplant ineligibility in multiple myeloma trials is often based on arbitrary age limits rather than a patient’s true health or fitness. This lack of clear, evidence-based definitions makes it harder to compare studies and may lead to unequal treatment decisions. Using standardized frailty and health assessments—rather than age alone—could help ensure patients receive the most appropriate care. 

Reference: 
Neupane K, Singstock M, Shah D, Dahal R, Mian H, Smith F, et al. Inconsistent definitions of transplant ineligibility in multiple myeloma: A systematic review. Br J Haematol. 2026; 00: 1–8. https://doi.org/10.1111/bjh.70323  (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70323)  
 
 

Navigating the evolving management of smoldering multiple myeloma – HemaSphere (January 2026) 

Background 
Smoldering multiple myeloma (SMM) is an early, symptom-free stage that lies between a monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma (MM). People with SMM have very different risks of developing MM—some progress quickly, while others may never need treatment. Because of this, accurately estimating each person’s risk is essential. 
 
How risk assessment has changed 
In the past, doctors estimated risk mainly using static clinical markers, such as the amount of abnormal protein in the blood, which reflects how much cancer is present. While helpful, these tools did not fully explain why some people progress, and others do not. 

New research has shown that: 
    • Genetic changes in myeloma cells 
    • Changes in the immune system 
    • Evolution of cancer cell subclones over time  
 

All play important roles in whether SMM progresses to active MM. This has led to more biologically informed risk models that better capture the complexity of the disease. 

Treatment: Watchful waiting vs early therapy 
Traditionally, SMM has been managed with watchful waiting, meaning close monitoring without treatment. Recent clinical trials, however, suggest that early treatment may benefit some people with high-risk SMM, challenging this long-standing approach. 
    • The FDA has approved lenalidomide with dexamethasone for certain high-risk SMM patients. 
    • The Oncologic Drugs Advisory Committee (ODAC) has recommended approval of daratumumab for high-risk SMM. 
    • Despite this, early treatment remains controversial, as doctors must balance the risk of treating too early against the risk of delaying therapy in people likely to progress. 

Current recommended approach 
Experts now suggest: 
    1. Clinical trial participation whenever possible, especially trials that include advanced diagnostic testing. 
    2. Careful observation first in many cases, to understand how the disease behaves over time. 
    3. Personalized decision-making, guided by evolving biomarkers and patient preferences. 

Looking ahead 
Researchers are working to improve risk prediction by combining clinical, genetic, molecular, and immune data, and by reassessing risk over time rather than at diagnosis alone. Future studies aim to clarify: 
    • Who truly benefits from early treatment 
    • How early therapy affects later treatment options 
    • Whether some high-risk patients should receive full myeloma treatment rather than preventive approaches 

Why this matters 
Smoldering multiple myeloma is no longer viewed as a single, uniform condition. It is now understood as a biologically diverse disease that requires personalized monitoring and treatment strategies. Ongoing research is essential to ensure that patients receive the right treatment at the right time—without unnecessary harm. 
 
Reference: 
Hammami, M.B., Canevarolo, R.R., Silva, A.S., Alsina, M., Kumar, N., Baz, R. and Shain, K.H. (2026), Navigating the evolving management of smoldering multiple myeloma. HemaSphere, 10: e70275. https://doi.org/10.1002/hem3.70275  (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70275)

Research 

Survival impact of anti-CD38-based quadruplet regimens in transplant-ineligible newly diagnosed multiple myeloma: a network meta-analysis and reconstructed individual patient data meta-analysis — Blood Cancer Journal (December 2025) 
 

Background 
People with newly diagnosed multiple myeloma who cannot undergo a stem cell transplant are usually treated with combinations of medicines. Newer treatments add an anti-CD38 antibody (such as daratumumab or isatuximab) to standard drugs, creating a four-drug (“quadruplet”) regimen. Until now, it was unclear whether these stronger combinations help patients live longer compared with standard three-drug (“triplet”) regimens. 
 
What is the purpose of the study?  

Researchers reviewed and combined results from four high-quality clinical trials including 2,038 patients. They compared quadruplet treatments with triplet treatments and looked at: 
    • Progression-free survival (PFS): how long the cancer stays under control 
    • Overall survival (OS): how long patients live 
 
Key results 
    • Quadruplet treatments kept the disease under control much longer than triplets. About 65% of patients on quadruplets were progression-free at 5 years, compared with 46% on triplets. 
    • Quadruplets also helped patients live longer. About 73% of patients on quadruplets were alive at 5 years, compared with 67% on triplets. 
    • Both daratumumab-based and isatuximab-based quadruplets performed similarly well. 
    • Among triplet options, those including an anti-CD38 drug were better than those without one. 
 
Why this study matters 
    • Using four drugs—including an anti-CD38 antibody—reduces the risk of the cancer worsening or causing death, even in older patients who cannot have a transplant. 
    • These benefits were consistent across different analyses, making the findings reliable. 
 
Important notes 
    • Very elderly or frail patients were underrepresented in some trials, so results should be applied carefully in those groups. 
    • No single trial directly compared all treatments, but advanced statistical methods were used to make fair comparisons. 
 
Bottom line  

For patients with newly diagnosed multiple myeloma who cannot receive a transplant, anti-CD38–based quadruplet therapy offers the best chance for longer disease control and longer life. When possible and well tolerated, these regimens should be considered a leading first-line treatment option. 
 
Reference: 
Souto Filho, J.T.D., Cantadori, L.O., Crusoe, E.d.Q. et al. Survival impact of anti-CD38-based quadruplet regimens in transplant-ineligible newly diagnosed multiple myeloma: a network meta-analysis and reconstructed individual patient data meta-analysis. Blood Cancer J. 15, 212 (2025). https://doi.org/10.1038/s41408-025-01413-7  (https://www.nature.com/articles/s41408-025-01413-7)
 
 

Talquetamab-Related Dysgeusia in Multiple Myeloma Compared to BCMA-Targeted Bispecifics and High-Dose Melphalan — Cancer Medicine (December 2025) 

What is the purpose of the study? 
Some treatments for multiple myeloma can change how food tastes, a problem called dysgeusia. This study looked at how often and how severe taste changes occur with different myeloma treatments, especially talquetamab (TAL), and compared them with high-dose melphalan with stem cell transplant (MEL/ASCT) and BCMA-targeted bispecific antibodies. 
 
How was the study conducted? 
    • 87 patients with multiple myeloma were tested for taste and smell. 
    • Patients also completed questionnaires about eating, quality of life, mood, and how side effects affected their treatment. 
 
Key findings 
    • Talquetamab caused the most severe taste problems:96% of patients on TAL reported major taste changes. 
    • Taste problems were also seen with: 
      - Melphalan/ASCT: about 63% of patients 
      - BCMA bispecifics: about 31% of patients 
    • Dry mouth was most common with TAL. 
    • Nausea, vomiting, and loss of appetite were more common with melphalan. 
    • Smell was mostly not affected, suggesting taste changes were the main issue. 
 
Impact on daily life 
    • Many patients said food became unpleasant, which affected nutrition, mood, and quality of life. 
    • About 30% of patients on TAL considered stopping treatment, mainly because of taste problems. 
    • Taste changes also affected social life and emotional well-being. 
 
Why this study matters 
    • Taste problems can lead to poor eating, weight loss, and lower quality of life, and may make it harder for patients to continue treatment. 
    • With TAL, taste changes appear to be linked to its action on tissues in the mouth and salivary glands. 
 
What can help 
    • Early recognition of taste problems 
    • Nutritional counseling and practical eating strategies 
    • Managing dry mouth and other mouth-related symptoms 
    • Emotional and psychological support 
 
Bottom line  

Taste changes are a major and often underestimated side effect, especially with talquetamab. Better monitoring, supportive care, and targeted strategies are needed to help patients cope, maintain nutrition, and stay on effective treatment. 
 
Reference: 
A. Fleischer, M. Roll, J. H. Frenking, et al., “ Talquetamab-Related Dysgeusia in Multiple Myeloma Compared to BCMA-Targeted Bispecifics and High-Dose Melphalan,” Cancer Medicine 14, no. 23 (2025): e71401,  https://doi.org/10.1002/cam4.71401 (https://onlinelibrary.wiley.com/doi/10.1002/cam4.71401). 

Uncovering the ultra-frail: A distinct subgroup in non-transplant eligible newly diagnosed patients with multiple myeloma, with an inferior clinical outcome — HemaSphere (December 2025) 

Background 
Older or less fit people with newly diagnosed multiple myeloma who cannot receive a stem cell transplant are often described as “frail.” However, this study shows that not all frail patients are the same, and their outcomes can differ greatly depending on why they are frail. 
 
How was the study conducted?  

Using data from two large clinical trials (202 patients total), researchers divided frail patients into three clear groups: 
    1. Frail by age only – over 80 years old but otherwise relatively healthy 
    2. Frail by health problems – younger than 80 but with other illnesses or daily function problems 
    3. Ultra-frail – over 80 and with other illnesses or functional impairments 

They then compared how long patients lived and how well they tolerated treatment. 
 
Key findings 
    • Ultra-frail patients did much worse than the other groups: 
      - Cancer returned sooner 
      - Average survival was about 2 years 
      - Higher risk of dying early (within the first 2 months of treatment) 
      - More severe side effects 
      - More likely to stop treatment early 
      - Less likely to receive later treatments if the cancer returned 
    • Patients who were frail by age alone lived the longest, with survival close to 4 years. 
    • Patients frail due to health problems had outcomes between the other two groups. 
    • These differences remained even after accounting for disease severity and lab values. 
 
Why this study matters 
    • Simply labeling someone as “frail” is not enough. 
    • Understanding why a patient is frail helps doctors: 
      - Better predict outcomes 
      - Avoid overly harsh treatments in the most vulnerable patients 
      - Tailor treatment intensity to improve safety and quality of life 
    • Ultra-frail patients are at the highest risk and need especially careful, individualized treatment and support. 
    • Frailty should be broken down into meaningful subgroups, not treated as a single category. 
 
Bottom line  

Frail patients with multiple myeloma are very different from one another. Those who are “ultra-frail” have much poorer outcomes and higher treatment risks. Recognizing these differences can help doctors choose safer, more personalized treatment plans and improve care for this vulnerable group. 
 
Reference: 
Groen, K., Smits, F., Nasserinejad, K., Levin, M.-D., Regelink, J.C., Timmers, G.-J., de Waal, E.G.M., Westerman, M., Velders, G.A., de Heer, K., Leys, R.B.L., van Kampen, R.J.W., Stege, C.A.M., Seefat, M.R., Nijhof, I.S., van der Spek, E., Klein, S.K., van de Donk, N.W.C.J., Ypma, P.F. and Zweegman, S. (2025), Uncovering the ultra-frail: A distinct subgroup in non-transplant eligible newly diagnosed patients with multiple myeloma, with an inferior clinical outcome. HemaSphere, 9: e70268. https://doi.org/10.1002/hem3.70268 (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70268) 

Genomically Smoldering Multiple Myeloma Is Not a Distinct Entity But a Collection of Monoclonal Gammopathy of Undetermined Significance or Multiple Myeloma — Journal of Clinical Oncology (December 2025) 
 

Background 
Smoldering multiple myeloma (SMM) is an early, symptom-free stage of multiple myeloma (MM). Doctors usually assess risk using clinical tests, but this study looked at whether genetic (genomic) features can better predict who will progress to active myeloma. 
 
How was the study conducted? 
Researchers analyzed DNA from bone marrow plasma cells in people with SMM, including patients who later developed MM, and compared them with patients who had newly diagnosed MM. 
 
Findings 
They found that in patients whose SMM progressed, the cancer cells already had most of the genetic changes seen in full myeloma—even before symptoms appeared. In contrast, people whose SMM did not progress had fewer genetic changes, lacked certain chromosome abnormalities, and showed overall more stable genomes. 

Using these genetic differences, the researchers developed a genomic scoring system that accurately identified patients with low-risk SMM who were unlikely to progress. This system worked well in additional patient samples and added useful information when combined with standard clinical risk tools. 

In summary  

Some cases of SMM are genetically very similar to multiple myeloma and are likely to progress, while others resemble a much milder condition and may remain stable for years. Genetic testing could help better classify SMM, guide monitoring and treatment decisions, and improve the design of future clinical trials. 
 
Reference: 
Anil Aktas Samur et al. Genomically Smoldering Multiple Myeloma Is Not a Distinct Entity But a Collection of Monoclonal Gammopathy of Undetermined Significance or Multiple Myeloma. J Clin Oncol 0, JCO-25-00289 DOI:10.1200/JCO-25-00289  (https://ascopubs.org/doi/10.1200/JCO-25-00289)

Selective depletion of B-cell subsets underlies increased risk of infection in MM patients treated with anti-BCMA vs -GPRC5D bsAbs — Blood (December 2025) 
 

Background 
Two types of bispecific antibody treatments used in multiple myeloma target different proteins: BCMA and GPRC5D. These proteins are found on cancerous plasma cells, but they are not distributed the same way on normal immune cells. 
 
Key findings 
This study found that BCMA is present not only on myeloma cells, but also on many normal B cells, including very early B-cell precursors and mature B cells.  
 
In contrast, GPRC5D is mainly found on plasma cells, both normal and cancerous, and not on earlier B cells. 
 

Because of this difference: 
    • Anti-BCMA treatments remove a wide range of B cells, including early B cells, mature B cells, and normal plasma cells. 
    • Anti-GPRC5D treatments mainly remove plasma cells and largely spare other B cells. 

This helps explain why infections are more common and sometimes more severe with anti-BCMA therapies. By removing many types of B cells that are needed to make antibodies, anti-BCMA treatments weaken the immune system more broadly. 

In summary 
Anti-BCMA therapies affect both cancer cells and normal immune cells, increasing infection risk, while anti-GPRC5D therapies are more selective. Understanding these differences may help doctors choose the most appropriate treatment, better prevent infections, and design more personalized therapy strategies for people with multiple myeloma. 
 
Reference: 
Tomas Jelinek, David Žihala, Aintzane Zabaleta, Ioannis V Kostopoulos, Ondrej Soucek, Ondrej Venglar, Cristina Moreno, Despina Fotiou, Eva Radova, Luis-Esteban Tamariz-Amador, Foteini Theodorakakou, Ludmila Muronova, Andrea Manubens, Ourania Tsitsilonis, Tereza Popková, Carmen Gonzalez, Anjana Anilkumar Sithara, Francesco Corrado, Nayda Bidikian, Camila Guerrero, Veronika Kapustova, Daniel Bilek, Patrick Ryan Hagner, Marta Larrayoz, Jose A Martínez-Climent, Lucie Broskevičová, Jana Mihalyova, Maximillian Merz, Tereza Sevcikova, Irene M. Ghobrial, Jesús F. San-Miguel, Meletios A Dimopoulos, Paula Rodriguez-Otero, Jakub Radocha, Efstathios Kastritis, Bruno Paiva, Roman Hajek; Selective depletion of B-cell subsets underlies increased risk of infection in MM patients treated with anti-BCMA vs -GPRC5D bsAbs. Blood 2025; blood.2025029572. doi: https://doi.org/10.1182/blood.2025029572  (https://ashpublications.org/blood/article/doi/10.1182/blood.2025029572/557373/Selective-depletion-of-B-cell-subsets-underlies)
 
 

An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden – Blood (December 2025) 
 

Background  

In multiple myeloma, bispecific T-cell engager (TCE) therapies help the immune system attack cancer cells. These treatments work well for many patients, but they are less effectiv and riskier when there is a high amount of cancer in the body. 
 

What this study found 
    • Strongly activating T cells by combining TCEs with certain immune-boosting drugs can improve cancer responses when tumor burden is high. 
    • However, too much immune activation can cause a dangerous side effect called cytokine release syndrome (CRS), which can be life-threatening. 
 

A safer and more effective approach 
    • Giving immune-modulating drugs (called CELMoDs, such as iberdomide) together with the steroid dexamethasone before starting TCE therapy helped “reset” the immune cells in the bone marrow. 
    • This pretreatment brought in healthier, less-exhausted T cells and reduced harmful immune reactions. 
    • When TCE therapy was given afterward, all subjects responded, survival was longer, and the risk of severe CRS was lower. 

Why this matters  

Carefully preparing the immune system before TCE treatment may make these therapies work better and more safely for patients with advanced multiple myeloma, especially those with a high amount of cancer. 
 
Reference: 
Erin W. Meermeier, Kirsten Pfeffer, Caleb K. Stein, Meaghen E. Sharik, Megan T. Du, Yuliza Tafoya Alvarado, Chang-Xin Shi, Yuan Xiao Zhu, P. Leif Bergsagel, Marta Chesi; An immunostimulatory CELMoD combination overcomes resistance to T-cell engagers caused by a high multiple myeloma burden. Blood 2025; 146 (25): 3072–3085. doi: https://doi.org/10.1182/blood.2025029215  (https://ashpublications.org/blood/article-abstract/146/25/3072/546908/An-immunostimulatory-CELMoD-combination-overcomes?redirectedFrom=fulltext)
 
 

Cytogenetic Testing in Newly Diagnosed Multiple Myeloma: Real World Evidence on Clinical Features and Adverse Outcomes for High-Risk Groups — Clinical Lymphoma Myeloma and Leukemia (December 2025) 
 

Background  

Some genetic changes in multiple myeloma make the disease more aggressive. The International Myeloma Society and the International Myeloma Working Group (IMS-IMWG) recently updated their definition of high-risk multiple myeloma. They clarified that a gain of chromosome 1q is considered high risk only when it occurs together with loss of part of chromosome 1p, and that certain immunoglobulin heavy chain (IgH) gene changes—t(4;14), t(14;16), and t(14;20)—are classified as high risk only when they are also accompanied by gain(1q) or loss of 1p. 

What is the purpose of the study? 
Researchers analyzed data from nearly 6,000 people newly diagnosed with multiple myeloma in Australia and New Zealand. Genetic test results were available for more than half of these patients. They compared symptoms, treatment responses, and survival based on how many high-risk genetic changes each patient had. 

Key findings 
    • Patients with more high-risk genetic changes were sicker at diagnosis, with lower blood counts, higher calcium levels, more cancer in the bone marrow, and other markers of aggressive disease. 
    • The more high-risk genetic changes a patient had, the shorter their time before the disease worsened and the shorter their overall survival. 
    • Initial responses to treatment were similar, but responses did not last as long in patients with more high-risk genetic changes. 
    • Each high-risk genetic change worsened outcomes, especially loss of part of chromosome 17 (del17p), which was linked to the poorest survival. 

Why this matters  

The number and type of high-risk genetic changes strongly affect outcomes in multiple myeloma. Careful genetic testing can help doctors better predict prognosis and choose more personalized treatment strategies. 
 
Reference: 
Ghassan Zammar, Bradley Augustson, Elizabeth Moore, Cameron Wellard, Elham Ashrafi, Hasib Sidiqi, Kenneth J C Lim, Dejan Radeski, Alannah Jackson, Krystal Bergin, Simon Harrison, P Joy Ho, Tracy King, Hang Quach, Peter Mollee, Rajeev Rajagopal, Brian Rosengarten, Erica Wood, Zoe McQuilten, Andrew Spencer, Cytogenetic Testing in Newly Diagnosed Multiple Myeloma: Real World Evidence on Clinical Features and Adverse Outcomes for High Risk Groups., Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.005 (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)04300-9/abstract). 
 

Real-world outcomes of high dose melphalan and autologous stem cell transplantation in patients with multiple myeloma older and younger than 65 years — Clinical Lymphoma Myeloma and Leukemia (December 2025) 
 

What is the purpose of the study? 
High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) is a common treatment for people with newly diagnosed multiple myeloma. This study looked at how well this treatment works in everyday practice for people older than 65 years compared with younger patients. 
 
How was the study conducted? 
Researchers studied 394 patients treated between 2013 and 2022 in the Netherlands. Of these, 109 were older than 65 years and 285 were 65 years or younger. The two groups were similar at the start of treatment. 
Main findings 
    • People over 65 lived just as long as younger patients after HDT/ASCT. 
    • The time until further treatment was needed was also similar between age groups. 
    • Serious side effects and treatment-related deaths were rare (about 1%). 
    • Long-term quality of life was stable or improved over time and was similar in older and younger patients. 

What this means  

For patients who are fit enough, age alone should not be a reason to avoid HDT/ASCT. The treatment is safe, effective, and well tolerated in selected patients over 65 years, with outcomes comparable to those in younger people. These results support offering HDT/ASCT to older patients with multiple myeloma when they are otherwise suitable for the treatment. 

Reference: 
Koen M. Klomberg, Miriam Gelderloos, Hilde A.M. Kooistra, Marcel Nijland, Geertruida H. de Bock, Gerwin A. Huls, Mirian Brink, Wilfried W.H. Roeloffzen, Wouter J. Plattel, Real-world outcomes of high dose melphalan and autologous stem cell transplantation in patients with multiple myeloma older and younger than 65 years, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.12.007.  (https://www.sciencedirect.com/science/article/pii/S2152265025043022) 
 

Prognostic value of serological and PET/CT response kinetics in patients with multiple myeloma treated with BCMA CAR-T — Leukemia (December 2025) 
 

Background  

CAR-T cell therapy that targets BCMA is an effective treatment for people with multiple myeloma whose disease has come back or stopped responding to other treatments. Many patients respond quickly, but it has been unclear which early test results best predict long-term benefits. 

What the study did  

Researchers reviewed 158 patients treated with BCMA CAR-T therapy at one hospital (2016–2024). They looked at: 
    • Blood test responses at 1 month and 3 months after treatment. 
    • PET/CT scans (a type of imaging test) before treatment and at follow-up in some patients.  They then compared these early results with how long patients lived without the disease worsening and overall survival. 
 

Key findings 
    • Early blood test improvement mattered most. 
      - Patients who had a very good response by 1 month or a complete response by 3 months lived longer and stayed in remission longer. 
      - This was true even for patients with more aggressive disease outside the bones. 
    • Certain high-risk features reduced the chance of early response, including disease outside the bone marrow and high levels of a blood marker (LDH) before treatment. 
    • PET/CT scans early after treatment (at 1 month) did not reliably predict outcomes. 
      - PET/CT results seemed more helpful later (3–12 months), especially when combined with a complete blood test response. 
    • Disease outside the bone marrow seen on PET/CT before treatment, especially with high activity on the scan, was linked to worse outcomes. 

What this means for patients 
    • How well the disease responds early on in blood tests is a strong signal of long-term benefit from BCMA CAR-T therapy. 
    • Patients who do not show a strong early response may benefit from additional or follow-up treatments, which are now being studied in clinical trials. 
    • PET/CT scans may still be useful, but their value appears greater later after treatment, not right away. 

Bottom line  

Early improvement in blood tests—within the first 1–3 months after BCMA CAR-T therapy—is the clearest sign of longer remission and survival. These results support using early response to guide follow-up care and future treatment decisions. 

Reference: 
Gustine, J.N., Scaringi, J.A., Bauer, F. et al. Prognostic value of serological and PET/CT response kinetics in patients with multiple myeloma treated with BCMA CAR-T. Leukemia (2025). https://doi.org/10.1038/s41375-025-02819-9  (https://www.nature.com/articles/s41375-025-02819-9)  
 

 
Structured whole-body MRI highlights clinically relevant disease pattern changes in relapsed/refractory multiple myeloma — Leukemia (December 2025) 
 

Background 
Whole-body MRI scans are an important tool for evaluating multiple myeloma. Most existing MRI scoring systems were designed for patients at first diagnosis, and it has been unclear how well they work for patients with relapsed/refractory multiple myeloma (RRMM). 
 
What is the purpose of the study? 
In this study, researchers compared MRI scans from patients with RRMM to those from newly diagnosed patients. Even though both groups had a similar overall amount of disease, the pattern of disease was different. Patients with RRMM were much more likely to have disease growing outside the bone marrow or next to bones, and less likely to have widespread involvement throughout the bone marrow. 
 
These differences are important because standard bone marrow biopsies are usually taken from the hip bone. In RRMM, such biopsies may miss disease located elsewhere, leading to an underestimation of how much cancer is present. This is especially relevant when doctors assess how well treatment has worked or whether very small amounts of disease remain. 
 
Results 
The study also showed that two MRI scoring systems (MY-RADS and KIM) were still useful in RRMM. Higher scores were linked to shorter survival and faster disease progression. Disease outside the bone marrow was a particularly strong sign of more aggressive illness and worse outcomes. 
 
In summary 
Overall, the results suggest that relapsed myeloma often becomes less dependent on the bone marrow and more aggressive in its growth pattern. Because of this, whole-body imaging should be used alongside bone marrow tests to better understand the disease, guide treatment decisions, and improve risk assessment for patients with RRMM. 
 
Reference: 
Grözinger, M., Schlanke, M., Gröne, J. et al. Structured whole-body MRI highlights clinically relevant disease pattern changes in relapsed/refractory multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02834-w (https://www.nature.com/articles/s41375-025-02834-w) 
 

Progressive NK-cell dysfunction and ILC imbalance favor immune evasion in multiple myeloma — Blood Advances (December 2025) 
 

Background 
Multiple myeloma (MM) is a cancer that weakens the immune system over time, allowing the disease to come back even after treatment. While problems with T cells are well known, this study focused on changes in the innate immune system, especially natural killer (NK) cells and other innate lymphoid cells (ILCs), which normally help the body detect and destroy cancer cells. 
 
What is the purpose of the study? 

Researchers examined blood and bone marrow samples from healthy people and from patients at different stages of myeloma—from early conditions (MGUS and smoldering myeloma) to newly diagnosed MM—to see how immune cells change as the disease progresses. 
 
Key findings 
    • NK cells increased in number as myeloma advanced, but worked less effectively. 
    • These NK cells lost key “activation” signals and gained “inhibitory” signals, making them less able to kill cancer cells. 
    • Many NK cells lost CD16, a molecule needed for common antibody treatments (like daratumumab and isatuximab) to work properly. This may help explain why some patients respond poorly to these drugs. 
    • Another helpful immune cell type, ILC1, decreased as myeloma progressed, weakening anti-cancer immune responses. 
    • In contrast, ILC2 cells increased. These cells are linked to immune suppression and may help the cancer survive and resist treatment. 
    • Changes in inflammatory signals (cytokines) in the blood and bone marrow supported this shift toward an immune environment that favors cancer growth. 
 
Why this matters  

Together, these changes create an immunosuppressive environment that allows myeloma to escape immune control and become resistant to treatment. 
 
What this could mean for future care 
    • Measuring NK cells and ILCs could help predict prognosis and treatment response. 
    • New strategies that restore NK cell function, protect or increase CD16, or rebalance ILC types may improve outcomes. 
    • These findings support the development of NK cell–based therapies, including engineered NK cells that may work alongside existing antibody treatments. 
 
Bottom line  

As multiple myeloma progresses, key immune cells become less effective or shift toward helping the cancer survive. Targeting these immune changes may lead to better, more personalized treatments and help overcome drug resistance. 
 
Reference: 
Maria Teresa Bilotta, Antonio Giovanni Solimando, Vanessa Desantis, Lucia Di Marzo, Andrea Sabatini, Sergio Forcelloni, Alessandro Andriano, Arcangelo Morizio, Antonella Argentiero, Roberto Ria, Linda Quatrini, Lorenzo Moretta, Paola Vacca, Nicola Tumino; Progressive NK-cell dysfunction and ILC imbalance favor immune evasion in multiple myeloma. Blood Adv 2025; 9 (24): 6246–6251. doi: https://doi.org/10.1182/bloodadvances.2025016659  (https://ashpublications.org/bloodadvances/article/9/24/6246/547195/Progressive-NK-cell-dysfunction-and-ILC-imbalance)  
 
 

Systemic bone loss measured by routine CT is associated with increased pain, postural decompensation, and survival in multiple myeloma – European Spine Journal (December 2025) 
 

What is the purpose of the study?  

People with multiple myeloma (MM) often lose bone strength, especially in the spine. CT scans, which many patients already have as part of routine care, can measure bone density using a value called the Hounsfield Unit (HU). Until now, it was unclear how changes in HU over time relate to pain, posture, daily function, and survival. 

How was the study conducted? 
The study reviewed 79 people with MM who had three routine whole-body CT scans over time. Bone density was measured in the lower spine (L1–L4). The researchers looked at how HU values changed and how these changes related to disease activity, treatments (such as steroids or bone-protective drugs), kidney and nutrition status, pain, posture, and survival. 

Key findings 
    • Bone density in the spine steadily decreased over time in most patients. On average, HU values dropped by more than 40% from the first to the last scan. 
    • Bone loss was greater in patients with: 
      - More active myeloma 
      - Long-term steroid treatment 
      - Kidney problems or poor nutritional status 
    • Bone loss was less severe in patients receiving bone-protective treatments (such as bisphosphonates or denosumab). 
    • A drop of 35% or more in HU was identified as a meaningful warning sign. Patients with this level of bone loss: 
      - Reported more back pain 
      - Needed stronger pain medications 
      - Showed worsening spinal posture (more stooping and loss of normal spinal curves) 
    • This level of bone loss was not always linked to visible fractures, suggesting that bone weakening can cause pain and posture problems even before fractures occur. 
    • Patients with large HU declines also showed a trend toward shorter overall survival, although this finding needs confirmation in larger studies. 

What this means for patients  

Measuring HU on routine CT scans provides useful information about overall bone health in multiple myeloma. A large drop in HU (especially ≥35%) may signal increased risk of pain, posture problems, and general physical decline—even if scans do not yet show fractures. 

Why this matters in care  

Tracking HU changes could help doctors: 
    • Identify patients at higher risk earlier 
    • Review disease control and treatment side effects (especially steroids) 
    • Optimize bone-protective therapy, nutrition, and physical support 
    • Consider closer follow-up or additional supportive care 

In summary 
Bone loss in multiple myeloma is widespread, progressive, and clinically important. Simple measurements from standard CT scans can help detect patients who may need earlier or more intensive support to reduce pain, protect mobility, and improve quality of life. 
 
Reference: 
Kylies, J., Weisel, K., M. Ballhause, T. et al. Systemic bone loss measured by routine CT is associated with increased pain, postural decompensation, and survival in multiple myeloma. Eur Spine J (2025). https://doi.org/10.1007/s00586-025-09703-1   (https://link.springer.com/article/10.1007/s00586-025-09703-1) 
 

 
Impact of the kinetics of circulating anti-BCMA CAR-T cells and normal lymphocytes on the outcome of MM patients — HemaSphere (December 2025) 
 

What is the purpose of the study?  
CAR-T cell therapy that targets BCMA has greatly improved response rates in people with relapsed/refractory multiple myeloma (RRMM). However, long-term control is still limited: only about 2 out of 10 patients remain free of disease progression five years after treatment. This study looked for early signs that could help predict who is most likely to benefit from CAR-T therapy. 
 
How was the study conducted? 
Researchers studied 53 adults with RRMM treated with different anti-BCMA CAR-T products. They closely analyzed blood samples taken before CAR-T cells were collected, before infusion, and for up to two years afterward. Using very detailed blood tests, they measured cancer cells in the blood and many types of immune cells, including CAR-T cells themselves. 
 

Key findings 
    • CAR-T cells expanded in the blood after infusion, usually peaking around two weeks, and showed a very complex mix of different cell types. 
    • Surprisingly, the amount, type, and behavior of CAR-T cells after infusion did not predict how long patients stayed in remission. 
    • Instead, outcomes were mainly linked to the patient’s condition before CAR-T infusion: 
      - Higher numbers of certain healthy helper T cells (especially naïve CD4+ T cells and a subtype called Th22 transitional memory cells) at the time of cell collection were linked to longer remission and survival. 
      - The presence of circulating tumor plasma cells (myeloma cells found in the blood) before infusion was linked to a worse outcome. 
    • Using these three factors, the researchers created a simple risk score that, together with disease stage, could predict before treatment which patients were more likely to have long-lasting benefit from CAR-T therapy. 

What this means  

Long-term success after anti-BCMA CAR-T therapy seems to depend more on: 
    1. The patient’s immune system health before treatment, 
    2. How much cancer is present in the blood, 
    3. The stage of the disease, rather than on the specific features of the CAR-T cells after they are infused. 

Why this study matters  

These results suggest that using CAR-T therapy earlier in the disease course—when the immune system is stronger and tumor burden is lower—may lead to better outcomes. They also point to possible future strategies, such as improving immune health or reducing tumor burden before CAR-T therapy, to help more patients achieve long-lasting remission. 
 
Reference: 
Gutiérrez-Herrero, S., Martín-Martín, L., Herrero-García, M., Puertas, B., da Silva Barbosa, E., Mateos, M.V., López-Corral, L., González-Calle, V., Rey-Búa, B., Martín-López, A.Á., Pérez-López, E., Sánchez-Guijo, F., López-Parra, M., Puig, N., Orfao, A. and on behalf of the INCAR and Euroflow Consortium (2025), Impact of the kinetics of circulating anti-BCMA CAR-T cells and normal lymphocytes on the outcome of MM patients. HemaSphere, 9: e70277. https://doi.org/10.1002/hem3.70277  (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70277)
 

 

Emerging Real-World Treatment Patterns and Clinical Outcomes of Multiple Myeloma in Argentina and Brazil: Insights from the TOTEMM Study in the Private Healthcare Sector — Current Oncology (December 2025) 
 

What is the purpose of the study? 
This study looked at how people with multiple myeloma are treated in real life in Argentina and Brazil when they are unable to receive a stem cell transplant. Researchers analyzed medical records from private healthcare systems between 2018 and 2024, including 72 patients in Argentina and 892 patients in Brazil. 
 
How was the study conducted? 
Doctors used many different drug combinations, most often starting with three-drug treatments, usually based on the drug bortezomib. Over time, treatments became shorter, and more patients stopped treatment with each new round. 
 
Results 
More than 75% of patients had their cancer return within one year after starting the first treatment. Most relapses happened between the first and second treatments, and many patients were treated again with drugs they had already received. About two-thirds of patients showed disease worsening after the first treatment. 
As patients moved through more treatments, the risk of the cancer getting worse or of death increased steadily. Fewer patients were able to continue to later treatment lines. 

Why this study matters 
Overall, the study shows that current treatments often do not control the disease for long, even in private healthcare systems with better access to newer drugs. These results highlight a strong need for more effective and longer-lasting treatment options, especially when the disease comes back after the first treatment, to improve both survival and quality of life for people with multiple myeloma. 
 

Reference: 
Hungria, V., Maiolino, A., Pessoa de Magalhães, R. J., Filho, Pitombeira de Lacerda, M., Remaggi, G., Scibona, P., Seehaus, C., Brulc, E., Savoy, N., Fantl, D., Soares, C., Abreu, G., Queiroz, J., Bernardino, G., Tanaka, S., Carrizo, M., Simonovich, V. A., Bertoldo Teixeira Fernandes, T., & Aggarwal, B. (2026). Emerging Real-World Treatment Patterns and Clinical Outcomes of Multiple Myeloma in Argentina and Brazil: Insights from the TOTEMM Study in the Private Healthcare Sector. Current Oncology, 33(1), 16. https://doi.org/10.3390/curroncol33010016 (https://www.mdpi.com/1718-7729/33/1/16)   
 

Peripheral blood immune cell profiling and response to BCMA CAR-T cell therapy in relapsed refractory multiple myeloma — Blood Cancer Journal (January 2026) 
 

Background  
CAR-T cell therapy is an advanced treatment that has greatly improved outcomes for people with multiple myeloma whose disease has come back or stopped responding to other treatments. Most patients respond well at first, but for many, the cancer eventually returns. Researchers are trying to understand why some patients respond better than others. 
 
What is the purpose of the study? 
In this study, researchers examined whether the types and amounts of immune cells in the blood before CAR-T treatment could help predict how well patients respond. This was the largest study to date to look at this question in people with relapsed or refractory multiple myeloma receiving BCMA CAR-T therapy. 
 
How was the study conducted? 
The study included 110 patients treated at one center. Before CAR-T treatment, blood tests were used to measure different immune cells, including: 
    • CD4 “helper” T cells 
    • CD8 “killer” T cells 
    • B cells 
    • Natural killer (NK) cells 

Researchers focused on treatment response 90 days after CAR-T infusion. 

Key findings 
    • Many patients had abnormal immune cell levels before treatment. 
    • Patients were less likely to respond to CAR-T therapy if: 
      - Their CD4/CD8 ratio was below 1 (meaning fewer helper T cells compared with killer T cells). 
      - They had higher levels of CD8 T cells before treatment. 
      - They had low levels of B cells before receiving chemotherapy that prepares the body for CAR-T cells. 
    • These immune features did not clearly affect overall survival or how long patients stayed in remission, but they were linked to early treatment response. 

What this means 
The balance of immune cells in the blood before CAR-T therapy appears to matter. Having too few helper T cells or too many CD8 T cells may reduce the chance of a strong response to treatment. 
 
Why this study matters 
Simple blood tests done before CAR-T therapy may help identify patients who are at higher risk of not responding well. In the future, this information could: 
    • Help doctors personalize treatment plans 
    • Guide strategies to improve immune balance before CAR-T therapy 
    • Support the development of combination or pre-treatment approaches to improve outcomes 

Limitations 
This was a retrospective study (looking back at existing data), and the immune tests could not measure more detailed immune features. The findings need to be confirmed in larger, prospective studies. 
 
Conclusion 
This study suggests that certain immune cell patterns before CAR-T therapy are linked to how well patients respond. With further research, these insights may help improve CAR-T treatment success for people with multiple myeloma. 
 
Reference: 
Pandey, T., Mohan Lal, B., Alrawabdeh, J. et al. Peripheral blood immune cell profiling and response to BCMA CAR-T cell therapy in relapsed refractory multiple myeloma. Blood Cancer J. 16, 4 (2026). https://doi.org/10.1038/s41408-025-01443-1  (https://link.springer.com/article/10.1038/s41408-025-01443-1) 
 
 

Barriers to and Facilitators of Clinical Trial Participation in Multiple Myeloma — Blood Global Hematology (January 2026) 
 

Background 
Treatments for multiple myeloma have improved, but not all patients benefit equally. One reason is that many patients cannot take part in clinical trials, which limits access to new therapies and leads to trial results that may not reflect real-world patients. 
 
What is the purpose of the study? 
This study examined multiple myeloma clinical trials conducted between 2011 and 2021 and identified barriers to patient participation. Most trials enrolled patients in the United States (61%) and Europe or East Asia, while many other regions had little or no participation. This shows clear global inequalities in access to clinical trials. 

Through a review of published studies and interviews with international experts, the researchers identified four main types of barriers to trial participation: 
    • Clinical factors, such as strict eligibility criteria 
    • Patient-related factors, such as financial challenges or travel distance 
    • Physician-related factors, such as lack of awareness of available trials 
    • Structural factors, such as regulatory or healthcare system limitations 

Stakeholders from different regions agreed on key recommendations to improve trial access worldwide. These findings can guide future efforts to reduce inequalities, increase patient participation, and ensure that clinical trials better represent people living with multiple myeloma. 
 

Reference: 
Martin Kaiser, Saba Ul-Hasan, Jack Lewis, Federica Mirto, Alicia O’Neill, Yelak Biru, Cynthia Chmielewski, Katie Joyner, Elise Gamertsfelder; Barriers to and Facilitators of Clinical Trial Participation in Multiple Myeloma. Blood Global Hematology 2026; 100056. doi: https://doi.org/10.1016/j.bglo.2025.100056  (https://ashpublications.org/bloodglobal/article/doi/10.1016/j.bglo.2025.100056/565883/Barriers-to-and-Facilitators-of-Clinical-Trial) 

 

Sex differences in the clinical presentation of patients with newly diagnosed multiple myeloma — Cancer (January 2026) 
 

Summary 
Multiple myeloma affects men more often than women. This study looked at whether men and women differ in how the disease appears at the time of diagnosis. 

Researchers studied 850 people newly diagnosed with multiple myeloma and compared clinical features (such as disease stage and organ damage) and genetic changes between men and women, while accounting for age, race, lifestyle, and socioeconomic factors. 

Key findings 
    • Men were more likely to have more advanced disease at diagnosis than women. 
    • Compared with women, men more often had: 
         - Later-stage disease (Stage III) 
         - Higher levels of abnormal protein in the blood 
         - More organ damage, especially kidney problems and bone damage (lytic bone lesions)
         - A specific type of myeloma involving kappa light chains 
    • Men were less likely to have: 
         - Myeloma that involves only light chains 
         - Low bone density (osteopenia) 

Role of age 
    • Age influenced these differences: 
            - Older men showed the strongest differences overall. 
            - Younger men were more likely to have certain high-risk genetic changes. 
    • This suggests that sex and age together affect how myeloma develops and progresses. 

What this means  
Overall, men tend to have a higher tumor burden (more cancer in the body) at the time of diagnosis compared with women. These differences may be related to biological factors such as hormones, immune system differences, and how genetic changes accumulate with age. 

Why this study matters  
    • Understanding sex- and age-related differences in multiple myeloma may help: 
            - Improve early detection 
            - Refine risk assessment 
            - Guide more personalized treatment strategies for both men and women 

Limitations and next steps 
    • The study included a moderate number of patients, and some genetic data were missing. 
    • Larger studies are needed to confirm these findings and better understand why these differences exist. 

Conclusion 
This study provides new evidence that men are more likely than women to be diagnosed with multiple myeloma that is more advanced and damaging, and that age plays an important role in these differences. Future research may lead to better, more personalized care for people at risk of or newly diagnosed with multiple myeloma. 
 
Reference: 
Ong KL, Arnold KD, Wessel MC, et al. Sex differences in the clinical presentation of patients with newly diagnosed multiple myeloma. Cancer. 2026;e70192. doi:10.1002/cncr.70192  (https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70192)

Clinical Trials 

Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab — New England Journal of Medicine (December 2025) 
 

Background  

Some people with multiple myeloma develop tumors outside the bone marrow (“true extramedullary myeloma”). This form is hard to treat and often comes back after standard therapies. Earlier research suggested that combining two immune-based drugs, talquetamab and teclistamab, might work well in these patients. 

What was done  In this phase 2 study, 90 patients with drug-resistant, true extramedullary myeloma were treated with both drugs. The main goal was to see how many patients’ cancer responded to treatment. Researchers also looked at how long responses lasted, how long patients lived without the disease getting worse, overall survival, and side effects. 

Results 
    • About 8 out of 10 patients (79%) responded to treatment. 
    • Among those who responded, about two-thirds (64%) still had a response after 12 months. 
    • After 12 months, 61% of patients had no disease progression, and 74% were still alive. 
    • Common side effects included mouth-related symptoms (such as taste changes or dry mouth), immune-related reactions (cytokine release syndrome), and skin changes. 
    • Serious side effects were common, mainly affecting blood cells or causing infections. 
    • A small number of patients stopped treatment due to side effects, and some deaths were related to infection or treatment. 

Conclusion  

Most patients with this difficult-to-treat form of myeloma responded to the combination of talquetamab and teclistamab. However, serious side effects were frequent, similar to what has been seen when each drug is used alone. 
 

Reference: 
Kumar S, Mateos MV, Ye JC, Atrash S, Magen H, Quach H, Chu MP, Trudel S, Richter J, Rodríguez-Otero P, Chuah H, Gatt M, Medvedova E, Raza S, Yoon DH, Ishida T, Matous JV, Rosiñol L, Onodera K, Scott E, Heuck C, Zhang J, Henninger T, O'Rourke L, Thakkar P, Festa M, Huang L, Zhou J, Takamoto M, Pei L, Lu J, Au N, Krevvata M, Usmani SZ, Cohen YC; RedirecTT-1 Investigators Study Group. Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab. N Engl J Med. 2025 Dec 7. doi: 10.1056/NEJMoa2514752 (https://www.nejm.org/doi/10.1056/NEJMoa2514752).  

Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma — New England Journal of Medicine (December 2025) 
 

What is the purpose of the study?  

Teclistamab is an immune-based treatment that helps the body’s T cells attack myeloma cells. Daratumumab is another antibody treatment already known to improve survival in multiple myeloma. This study tested whether combining teclistamab with daratumumab works better than commonly used daratumumab-based treatments. 

How was the study conducted?  

In this phase 3 study, 587 patients with multiple myeloma who had already received 1–3 previous treatments were randomly assigned to one of two groups: 
    • Teclistamab plus daratumumab, or 
    • Standard treatment, which was daratumumab with dexamethasone plus either pomalidomide or bortezomib. 

The main outcome measured was how long patients lived without their disease getting worse. 

Results 
    • Patients receiving teclistamab plus daratumumab lived much longer without disease progression than those receiving standard treatment. 
    • After 3 years, 83% of patients in the teclistamab–daratumumab group had no disease progression, compared with 30% in the standard-treatment group. 
    • More patients in the teclistamab–daratumumab group had deep responses, including complete responses and very low or undetectable levels of cancer cells. 
    • Serious side effects were common in both groups and occurred slightly more often with teclistamab–daratumumab. Deaths related to side effects were uncommon and occurred at similar rates in both groups. 

Conclusion  

For patients with multiple myeloma who have already had 1–3 treatments, the combination of teclistamab and daratumumab controlled the disease much better than standard daratumumab-based therapies, though serious side effects were frequent. 

Reference: 
Costa LJ, Bahlis NJ, Perrot A, Nooka AK, Lu J, Pawlyn C, Mina R, Caeiro G, Kentos A, Hungria V, Reece D, Niu T, Mylin AK, Hansen CT, Teipel R, Besemer B, Dimopoulos MA, Zamagni E, Yoshihara S, Kim K, Min CK, Geerts P, Van Leeuwen-Segarceanu E, Tyczynska A, Reguera JL, Johansson M, Hansson M, Turgut M, Grey M, Sidana S, Rodriguez-Otero P, Martinez-Lopez J, Hashmi H, Carson R, Kobos R, Sun W, Lantz K, Seifert A, Briseno-Toomey D, O'Rourke L, Rubin M, Vieyra D, Kang L, Mateos MV; MajesTEC-3 Trial Investigators. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2025 Dec 9. doi: 10.1056/NEJMoa2514663.  (https://www.nejm.org/doi/10.1056/NEJMoa2514663) 
 

Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study — Journal of Clinical Oncology (December 2025) 
 

Background  

Venetoclax is an oral drug that targets a survival protein (BCL-2) used by some myeloma cells, especially in patients whose myeloma has a specific genetic change called t(11;14). Dexamethasone can make myeloma cells more sensitive to venetoclax. This study tested whether venetoclax plus dexamethasone works better than a standard treatment, pomalidomide plus dexamethasone. 

How was the study conducted?  

In this large phase 3 study, 263 adults with relapsed or refractory multiple myeloma and the t(11;14) genetic change—who had already received at least two prior treatments—were randomly assigned to receive either: 
    • Venetoclax plus dexamethasone, or 
    • Pomalidomide plus dexamethasone. 

The main goal was to see how long patients lived without their disease getting worse. 

Results 
    • Patients treated with venetoclax plus dexamethasone lived somewhat longer without disease progression (about 10 months) than those on pomalidomide plus dexamethasone (about 6 months), but this difference was not statistically significant. 
    • More patients responded to venetoclax plus dexamethasone (62% vs. 35%), and deeper responses were more common. 
    • A small number of patients had no detectable cancer cells after treatment with venetoclax, while none did with pomalidomide. 
    • Overall survival was slightly longer with venetoclax, but again not significantly different. 
    • Serious side effects were common in both groups. Infections, including some fatal infections, occurred more often with venetoclax plus dexamethasone. 

Conclusion  

This study did not show a clear survival advantage for venetoclax plus dexamethasone compared with pomalidomide plus dexamethasone in patients with t(11;14)-positive multiple myeloma. While venetoclax led to higher response rates, it also carried a higher risk of serious infections. These results do not support routine use of this combination but suggest that venetoclax may still be useful in carefully selected patients or in combination with other treatments. 
 
Reference: 
Rakesh Popat et al. Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study. J Clin Oncol 0, JCO-25-00924 DOI:10.1200/JCO-25-00924 (https://ascopubs.org/doi/10.1200/JCO-25-00924) 

Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study — Blood (December 2025) 
 

What is the purpose of the study?  

Talquetamab and daratumumab are immune-based treatments for multiple myeloma. Each works in a different way to help the immune system attack myeloma cells. Researchers studied whether using these two drugs together could improve results for patients whose myeloma had come back or stopped responding to many previous treatments. 

How was the study conducted?  

In this early phase (phase 1b) study, 65 patients with relapsed or refractory multiple myeloma—most of whom had already received many treatments—were given talquetamab plus daratumumab. Talquetamab was given either weekly or every other week, and daratumumab was given on its standard schedule. The main goal was to evaluate safety, while also looking at how well the treatment worked. 

Results 
    • About 7–8 out of 10 patients responded to the combination treatment. 
    • Responses lasted a long time, with patients living about 21–23 months on average without disease progression. 
    • The treatment worked even in patients who had previously received other advanced immune therapies. 
    • Side effects were common and included mouth problems, skin reactions, immune-related reactions (cytokine release syndrome), and infections. 
    • Serious side effects occurred in many patients, but the overall safety profile was similar to what is already known for each drug used alone. 

Conclusion  

In heavily pretreated patients with multiple myeloma, the combination of talquetamab and daratumumab showed strong and lasting responses. Side effects were frequent but expected. These results suggest this fully immune-based combination may be a promising treatment option for patients with difficult-to-treat multiple myeloma. 

Reference: 
Ajai Chari, Niels W. C. J. van de Donk, Bhagirathbhai Dholaria, Katja Weisel, María-Victoria Mateos, Hartmut Goldschmidt, Thomas G. Martin, Daniel Morillo, Donna Reece, Paula Rodríguez-Otero, Manisha Bhutani, Anita D’Souza, Albert Oriol, Laura Rosiñol, Nizar J. Bahlis, Deeksha Vishwamitra, Sheri Skerget, Raluca I. Verona, Kalpana Bakshi, Lijuan Kang, Thomas J. Prior, Lien Vandenberk, Jaszianne Tolbert, Sangmin Lee, M. Damiette Smit, Ralph Wäsch; Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study. Blood 2025; 146 (24): 2902–2913. doi: https://doi.org/10.1182/blood.2025029360  (https://ashpublications.org/blood/article-abstract/146/24/2902/547408/Talquetamab-plus-daratumumab-for-the-treatment-of?redirectedFrom=fulltext)
 
 

Daratumumab bortezomib and dexamethasone in transplant ineligible newly diagnosed elderly myeloma patients (AMN006)—a trial by Asian Myeloma Network (NCT03695744) — Leukemia & Lymphoma (December 2025) 
 

What is the purpose of the study? 
This study by the IMF’s Asian Myeloma Network (AMN) tested a three-drug treatment—daratumumab, bortezomib, and dexamethasone (DVd)—in older adults with newly diagnosed multiple myeloma who were not eligible for stem cell transplant. 
 
How was the study conducted? 
27 patients were treated with DVd for 9 months, followed by ongoing daratumumab alone as maintenance therapy. The main goal was to see how many patients responded to treatment, along with how long the treatment controlled the disease and how safe it was. 
 

After a little over two years of follow-up: 
    • 96% of patients responded to treatment 
    • About 30% achieved a complete response, and 52% had a very good partial response 
    • Most patients with a complete response had no detectable cancer cells using very sensitive testing 
    • The disease stayed under control for a median of about 3 years 
    • Overall survival was very good, with most patients still alive at the time of analysis 
    • Side effects related to treatment were relatively uncommon and manageable 

In summary  

A fixed-length course of DVd followed by daratumumab maintenance was effective, long-lasting, and generally well tolerated in older patients with newly diagnosed multiple myeloma who could not undergo transplant. This approach appears to be a promising first treatment option for this group. 

Reference: 
Tan, M. S. Y., Nagarajan, C., Ooi, M., De Mel, S., Binte Hashim, N. S., Li, X., … Chng, W. J. (2025). Daratumumab bortezomib and dexamethasone in transplant ineligible newly diagnosed elderly myeloma patients (AMN006)—a trial by Asian Myeloma Network (NCT03695744). Leukemia & Lymphoma, 1–8. https://doi.org/10.1080/10428194.2025.2602050 (https://www.tandfonline.com/doi/full/10.1080/10428194.2025.2602050)  
 

Toward functional cure in relapsed/refractory multiple myeloma: long-term outcomes from CARTITUDE-1 study cement the role of CAR-T cells – Bone Marrow Transplantation (December 2025) 

Background
New immune-based treatments that use a patient’s own T cells (especially CAR-T cell therapy and bispecific antibodies) have greatly improved outcomes for people with relapsed or treatment-resistant multiple myeloma. For some patients, these therapies can lead to very long-lasting remission, and may even offer the possibility of a cure. 

What is the purpose of the study?
The CARTITUDE-1 trial tested ciltacabtagene autoleucel (CARVYKTI®, cilta-cel) in patients whose myeloma had returned despite many previous treatments. These patients usually have very poor outcomes. Remarkably, after a single CAR-T infusion and no ongoing maintenance therapy, patients lived a median of about 5 years, far longer than expected. About one-third of patients remained free of disease progression for more than five years, and most of them had no detectable cancer using very sensitive tests. 

Key results
Some patients showed extremely deep and lasting responses, with no signs of disease on bone marrow tests or imaging scans even after five years. This supports the idea that a “functional cure”—long-term remission without ongoing treatment—may be possible for a selected group of patients. 

Researchers also learned why some patients did better than others. Long-lasting remission was more common in patients who: 
    • Had a lower amount of cancer at the time of treatment 
    • Had stronger immune systems (healthier blood counts and T cells) 
    • Produced CAR-T cells with better quality during manufacturing 

These findings may help doctors better select patients and improve future CAR-T treatments. 

Importantly, long-term safety was reassuring. No new serious late side effects were seen after five years, including serious nerve problems, and serious infections or second cancers were uncommon. 

Limitations
However, the study has limits. It did not compare CAR-T therapy with another treatment, included a relatively small and selected group of patients, and long-term testing was not always done in the same standardized way. This means results are very encouraging but may not apply to everyone with myeloma. 

Why this study matters

Newer studies are now testing cilta-cel earlier in the disease, where results look even better, with higher rates of deep remission. Trials are also exploring its use in newly diagnosed patients. 

In summary

CAR-T therapy with cilta-cel has changed expectations for people with hard-to-treat multiple myeloma. For some patients, a single treatment can lead to many years without disease or ongoing therapy, raising real hope that long-term remission (and possibly cure) is achievable. 
 
Reference: 
de Soto, T., Moukalled, N. & Mohty, M. Toward functional cure in relapsed/refractory multiple myeloma: long-term outcomes from CARTITUDE-1 study cement the role of CAR-T cells. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02782-0   (https://www.nature.com/articles/s41409-025-02782-0)

Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma — Blood Cancer Journal (December 2025) 
 

Background 
Kidney problems are a serious and common complication of multiple myeloma and are linked to worse survival. Recovering kidney function quickly can greatly improve outcomes, but patients with kidney impairment have often been left out of major treatment studies. 
 

What is the purpose of the study? 
The REMNANT study included newly diagnosed multiple myeloma patients who were eligible for stem cell transplantation, regardless of kidney function. In this analysis, all patients received four cycles of standard initial treatment with bortezomib, lenalidomide, and dexamethasone. Importantly, lenalidomide was given at higher doses than usually recommended for patients with reduced kidney function. 
 

Results 
About one in five patients had kidney impairment at diagnosis, including some who required dialysis. Most of these patients responded well to treatment: 77% showed improvement in kidney function, and more than half recovered normal kidney function. Five patients were able to stop dialysis. Cancer response rates were just as good in patients with kidney problems as in those with normal kidney function. 

Side effects
Side effects were generally manageable. Patients with kidney impairment had more anemia and low platelet counts, but serious treatment-related kidney worsening was rare and reversible. Very few patients stopped treatment because of side effects. 

In summary 
Overall, this study shows that lenalidomide can be safely and effectively used at full or moderately reduced doses during initial treatment, even in patients with significant kidney impairment, including those on dialysis. Treating the myeloma effectively and early can lead to meaningful recovery of kidney function and should not be withheld because of kidney disease. 
 
Reference: 
Askeland, F.B., Bugge, V.H., Rasmussen, AM. et al. Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma. Blood Cancer J. 15, 214 (2025). https://doi.org/10.1038/s41408-025-01407-5 (https://www.nature.com/articles/s41408-025-01407-5) 
 

Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO — Blood Cancer Journal (December 2025) 
 

What is the purpose of the study? 
The Phase 2 IZALCO study looked at how well, how safely, and how conveniently isatuximab works when given under the skin (subcutaneous, SC) together with carfilzomib and dexamethasone (Kd) in people with relapsed or refractory multiple myeloma. 
 
How was the study conducted? 
Isatuximab was given either by a standard manual injection or by a wearable on-body injector (OBI). Some patients switched between the two methods during the study, and after six treatment cycles, patients could choose the method they preferred. 

A total of 74 patients took part. Their median age was 65 years, and most had received one prior treatment. After about 10 months of follow-up, nearly 80% of patients responded to treatment, meeting the study’s main goal. 
Most patients (about 75%) preferred the on-body injector over manual injections. Importantly, the way the drug was given did not affect how well it worked, its safety, how the body processed the drug, or immune reactions. 

Conclusion 
Overall, the study shows that giving isatuximab under the skin using an on-body injector is effective, safe, and convenient for patients with relapsed or refractory multiple myeloma. 
 
Reference: 
Parmar, G., Capra, M., Seguro, F. et al. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO. Blood Cancer J. (2025). https://doi.org/10.1038/s41408-025-01436-0 (https://www.nature.com/articles/s41408-025-01436-0) 
 

Efficacy and safety of teclistamab in triple-class exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort — Cancer (January 2026) 
 

Background  

Teclistamab is a new type of antibody treatment approved for people with relapsed/refractory multiple myeloma (RRMM). It targets a protein on myeloma cells (BCMA) and has shown strong and lasting responses with manageable side effects. 

Methods  

Researchers analyzed results from three groups of patients: 
    • A global clinical trial group of 217 patients from studies in multiple countries 
    • An Asian clinical trial subgroup of 52 patients 
    • An Asian pre-approval access group of 42 patients who received teclistamab outside clinical trials before approval 

Results  

In the global clinical trial group, patients were a median age of 65 and had received about five prior treatments. After about 2.5 years of follow-up: 
    • About two-thirds of patients responded to treatment 
    • Half achieved a complete response or better 
    • The time before the disease worsened was about 16 months, and average survival was about 29 months 

In the Asian clinical trial group, patients had similar disease features but lower body weight. Results were at least as good: 
    • About 77% responded, and 64% achieved a complete response or better 
    • Most patients were still responding and alive at 2 years 

The Asian pre-approval group showed similar benefits. 

The most common side effects were low blood counts, immune reactions (cytokine release syndrome), and infections. Infection care improved over time, especially with greater use of protective immunoglobulin treatment. 

Conclusion  

Across different countries, body weights, and treatment settings, teclistamab provides meaningful and lasting benefits for heavily pretreated patients with multiple myeloma. These results support its use as an important treatment option for this difficult-to-treat disease. 

Reference: 
Martin TG, Mateos M-V, Yi JH, et al. Efficacy and safety of teclistamab in triple-class exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort. Cancer. 2026; e70237. doi:10.1002/cncr.70237  (https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70237)  
 

Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial — The Lancet Haematology (January 2026) 
 

Background  

Iberdomide is a new oral medicine that works on the immune system and cancer cells more strongly than similar drugs. This study looked at how safe and effective iberdomide combined with low-dose cyclophosphamide and dexamethasone (called IberCd) is for people with multiple myeloma whose disease has come back or no longer responds to standard treatments. 

How was the study conducted?  

In this Dutch phase 2 study, 61 adults with relapsed or treatment-resistant multiple myeloma received the IberCd combination. All medicines were taken by mouth in repeating 28-day cycles until the disease worsened. Patients had already been treated with 2 to 4 different therapies before joining the study. Researchers mainly measured how long patients lived without their disease getting worse, as well as side effects. 

Key results 
    • Patients were followed for about 25 months on average. 
    • The median time before the disease worsened was 17.6 months. 
    • Most patients had previously received several types of myeloma treatments, and many no longer responded to them. 
    • The most common serious side effects were low white blood cell counts and infections. 
    • Serious treatment-related side effects occurred in about 4 out of 10 patients. 
    • One patient died from COVID-19, which was considered treatment-related. 

Why this study matters  

IberCd is a fully oral treatment that shows meaningful benefits for patients with difficult-to-treat multiple myeloma. It appears to be an effective option for patients who have already received several prior treatments and compares well with other available therapies. 

Reference: 
Korst, Charlotte L B M et al. Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial. The Lancet Haematology, Volume 13, Issue 1, e30 – e40.  https://doi.org/10.1016/S2352-3026(25)00298-4  (https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00298-4/abstract) 

 

Belantamab mafodotin, pomalidomide, and dexamethasone in Japanese patients with RRMM in the phase 3 DREAMM-8 trial – International Journal of Hematology (January 2026) 
 

What is the purpose of the study? 
This study looked at a new treatment combination for people in Japan with relapsed or refractory multiple myeloma whose disease had already been treated with lenalidomide. 

Researchers compared two treatment options: 
    • BPd: belantamab mafodotin + pomalidomide + dexamethasone 
    • PVd: bortezomib + pomalidomide + dexamethasone 

A total of 21 patients were included and followed for about 14 months. 

Key results 
    • Patients who received BPd tended to stay in remission longer than those who received PVd. 
    • At 90 days, 90% of patients on BPd responded to treatment, compared with 73% on PVd. 
    • Deeper responses (very good partial response or better) were more common with BPd (70%) than with PVd (36%). 
    • Responses with BPd also tended to last longer, although follow-up is still ongoing. 

Safety and side effects 
    • Overall side effects were similar to those seen in international studies. 
    • Eye-related side effects (such as blurred vision or a gritty feeling) were common with BPd, affecting most patients. 
    • These eye problems were temporary and reversible, and no patients had to stop treatment because of them. 
    • Managing eye side effects usually involves pausing or delaying doses, which does not reduce treatment effectiveness. 
    • Infections were somewhat more common with BPd, but were manageable. 

Why this study matters 
Many patients today receive lenalidomide and anti-CD38 drugs early in treatment. When the disease stops responding to these therapies, options become limited. This study shows that BPd can be an effective treatment even in patients whose disease is resistant to prior therapies, including lenalidomide and daratumumab. 

Limitations 
    • The number of Japanese patients was small. 
    • Follow-up time was relatively short. 
    • The two treatment groups were not perfectly balanced at the start of the study. 

Conclusion 
For Japanese patients with relapsed or refractory multiple myeloma, BPd showed better treatment responses than PVd, with side effects that could be managed safely. These results match findings from the larger international study and support BPd as an important treatment option after relapse. 
 
Reference: 
Sunami, K., Handa, H., Ichii, M. et al. Belantamab mafodotin, pomalidomide, and dexamethasone in Japanese patients with RRMM in the phase 3 DREAMM-8 trial. Int J Hematol (2026). https://doi.org/10.1007/s12185-025-04150-6  (https://link.springer.com/article/10.1007/s12185-025-04150-6)

Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial — The Lancet Oncology (January 2026) 
 
 

What is the purpose of the study?  

CARTITUDE-4 was a large international clinical trial that compared a one-time CAR T-cell treatment called ciltacabtagene autoleucel (cilta-cel) with standard drug combinations in people with multiple myeloma whose disease no longer responded to lenalidomide and had come back after 1–3 prior treatments. 

Those who took part in the study include: 
    • Adults with relapsed or refractory multiple myeloma 
    • Previously treated with common myeloma drugs 
    • Good overall physical condition 
    • About 420 patients were enrolled worldwide 

What treatments were compared 
    • Cilta-cel: A single infusion of CAR T cells after short preparatory chemotherapy 
    • Standard of care: Ongoing treatment with commonly used drug combinations 

Key results after nearly 3 years of follow-up 
    • People who received cilta-cel lived longer than those who received standard treatments. 
    • Cilta-cel reduced the risk of death by about 45% compared with standard therapy. 
    • Many patients treated with cilta-cel stayed free of disease progression for much longer: More than half were alive and without disease progression at 30 months. 
    • A single cilta-cel infusion allowed many patients to go long periods without needing ongoing myeloma treatment. 
    • Quality of life was better overall, with symptoms worsening later compared with standard treatment. 

Safety 
    • Side effects were consistent with what is already known about CAR T-cell therapy. 
    • Low blood cell counts and infections were common, especially early on. 
    • Serious side effects occurred at similar rates in both groups. 
    • Deaths related to treatment were uncommon and mostly due to infections. 
    • Rare nerve-related side effects (such as movement problems) were uncommon and did not increase with longer follow-up. 

Why this study matters 
    • This is the first phase 3 study to show that CAR T-cell therapy helps patients with multiple myeloma live longer. 
    • The benefits were seen early in the disease course, as soon as the first relapse. 
    • Results suggest that giving CAR T-cell therapy earlier may lead to deeper, longer-lasting responses than standard treatments. 

Bottom line  

A single infusion of cilta-cel significantly improved survival, delayed disease progression, and improved quality of life compared with standard therapies in patients with lenalidomide-refractory multiple myeloma. These findings support using CAR T-cell therapy earlier in treatment, not only as a last resort. 

Reference: 
Hermann Einsele, Jesús San-Miguel, Binod Dhakal, Cyrille Touzeau, Xavier Leleu, Niels WCJ van de Donk, Surbhi Sidana, Albert Oriol, Yael C Cohen, Simon J Harrison, María-Victoria Mateos, Joaquín Martínez-López, Paolo Corradini, Lionel Karlin, Diana Chen, Quanlin Li, Tzu-min Yeh, Katherine Li, Vicki Plaks, Ana Slaughter, Carolina Lonardi, Nina Benachour, Arnab Ghosh, Martin Vogel, Jordan M Schecter, Nikoletta Lendvai, Mythili Koneru, Nitin Patel, Erika Florendo, Phoebe Joy Ho, Rakesh Popat, Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial, The Lancet Oncology, 2026, ISSN 1470-2045, https://doi.org/10.1016/S1470-2045(25)00653-9. (https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00653-9/fulltext) 
 

Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study — HemaSphere (January 2026) 
 

What is the purpose of the study? 
The EMN19 clinical trial tested a four-drug combination for patients with a specific, aggressive form of multiple myeloma. 
 
Some multiple myeloma patients develop extramedullary plasmacytomas—tumors that grow outside the bone marrow in soft tissues or near the bone. This form of the disease is harder to treat. Researchers tested a treatment "cocktail" called DaraVCD to see if it could help these high-risk patients. 

DaraVCD combination: 
    • Daratumumab: An antibody therapy that targets cancer cells. 
    • Bortezomib, Cyclophosphamide, and Dexamethasone: A mix of chemotherapy and steroid drugs. 
 

Key findings 
The study followed 40 patients (some newly diagnosed, some who had relapsed) for about 30 months. 
    • Strong response in new patients: Nearly 60% of newly diagnosed patients achieved a "complete response" (no detectable signs of cancer in the blood). 
    • Deep remission: Many patients reached MRD negativity, meaning that even highly sensitive tests could not find cancer cells in their bone marrow. 
    • Imaging success: About half of the patients achieved a "complete metabolic response," where PET/CT scans showed no active tumors. 
    • Survival: Patients who reached a complete response lived significantly longer without the disease progressing. For many of these "responders," the disease had still not returned by the end of the study. 
 
Safety and side effects 
The treatment was generally well-tolerated over the three-year period. 
    • Common side effects: Lowered blood counts (anemia or low platelets). 
    • Serious risks: The most common serious issues were infections. 
    • Sustainability: Only one patient had to stop the treatment due to side effects, suggesting the regimen is manageable for most. 
 

Why this study matters 
    1. This is the first study to focus specifically on patients with these external tumors using this four-drug combination. 
    2. The treatment worked quickly, often showing results within 4 to 5 months. 
    3. While the results were encouraging, progression-free survival (PFS) was still shorter than it is for patients who don't have these external tumors. This tells doctors that while DaraVCD is a good tool, even stronger treatments may be needed for this specific group. 

Bottom line 
DaraVCD is an effective and safe option for patients with multiple myeloma that has spread outside the bone marrow, especially for those who are newly diagnosed. 
 
Reference: 
Beksac, M., Fıratlı Tuglular, T., Gay, F., Mina, R., Katodritou, E., Unal, A., Cavo, M., Ozsan, G.H., van der Velden, V.H.J., Beverloo, B.H., Vermeulen, M., van Duin, M., Seval, G.C., Sevindik, O.G., Merante, S., Manousou, K., Sonneveld, P., Zamagni, E. and Terpos, E. (2026), Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study. HemaSphere, 10: e70287. https://doi.org/10.1002/hem3.70287  (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70287)
 

Comparative Effectiveness and Safety of PI-Rd Triplets in Relapsed/Refractory Multiple Myeloma: INSIGHT-MM Data Analysis — European Journal of Haematology (January 2026) 
 

What is the purpose of the study?  

This study looked at how well and how safely three proteasome inhibitor (PI)–based treatment combinations work for people with relapsed or refractory multiple myeloma (RRMM) in everyday clinical practice. The treatments were: 
    • IRd: ixazomib + lenalidomide + dexamethasone 
    • KRd: carfilzomib + lenalidomide + dexamethasone 
    • VRd: bortezomib + lenalidomide + dexamethasone 

The analysis used real-world data from the large international INSIGHT-MM observational study. 

How was the study conducted? 
Adults with RRMM who received IRd, KRd, or VRd as second-line or later therapy were included. In total, 348 patients contributed to 356 treatment courses. 

How was effectiveness measured?  

Researchers assessed outcomes such as: 
    • Real-world progression-free survival (rwPFS) – time before the disease worsened or treatment stopped 
    • Duration of treatment (DOT) 
    • Duration of response (DOR) 
    • Time to next treatment (TTNT) 
    • Overall survival (OS) 

Statistical methods were used to adjust for differences in patient characteristics between treatment groups. 

Key results 
    • Median rwPFS was: 
      - 14.5 months with IRd 
      - 13.2 months with KRd 
      - 9.1 months with VRd 
    • After adjusting patient differences, no significant differences in rwPFS were found between the three regimens. 
    • IRd and KRd tended to have longer treatment duration and response compared with VRd. 
    • All three regimens showed a manageable safety profile, consistent with previous clinical trials. 

How do these results compare with clinical trials?  

Outcomes such as PFS and OS were generally lower than those reported in phase 3 randomized clinical trials, which is expected because real-world patients are more diverse, older, and often have more health conditions. This study used rwPFS to reflect real-world clinical practice. 

Why this study matters  

The findings show that IRd, KRd, and VRd have similar effectiveness and safety in real-world settings. This means treatment choice should not be based on effectiveness alone, but also on: 
    • Patient age, frailty, and other health conditions 
    • Prior treatments (including stem cell transplant) 
    • Convenience (for example, IRd is an all-oral regimen) 
    • Side effects, patient preferences, and cost considerations 

Limitations  

As with all real-world studies, there were limitations, including smaller subgroup sizes, missing data, and differences in patient characteristics and treatment practices across regions. Some remaining bias may be present despite statistical adjustments. 

Overall conclusion  

In the INSIGHT-MM study, IRd, KRd, and VRd were all effective and safe options for treating RRMM in routine clinical practice. These results support a holistic, individualized approach when selecting a proteasome inhibitor–based treatment for patients with RRMM. 

Reference: 
N. Puig, X. Leleu, H. C. Lee, et al., “Comparative Effectiveness and Safety of PI-Rd Triplets in Relapsed/Refractory Multiple Myeloma: INSIGHT-MM Data Analysis,” European Journal of Haematology (2026): 1–13, https://doi.org/10.1111/ejh.70079 (https://onlinelibrary.wiley.com/doi/10.1111/ejh.70079). 
 

Positive results from Phase 3 MajesTEC-9 study reveal that Tecvayli monotherapy reduced risk of disease progression significantly vs standard of care, in RRMM patients refractory to anti-CD38 therapy and lenalidomide 
 

On Wednesday, January 14, Johnson & Johnson announced via press release that Tecvayli (teclistamab-cqyv) monotherapy “demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide,” based on “positive topline results from the investigational Phase 3 MajesTEC-9 study of Tecvayli monotherapy, which showed a 71% reduction in the risk of disease progression or death and a 40% reduction in the risk of death in a patient population that was predominantly refractory to anti-CD38 therapy and lenalidomide.” 

The Phase 3 MajesTEC-9 study tested Tecvayli monotherapy in people with relapsed or refractory multiple myeloma who had already been treated with, and no longer responded to, common therapies including anti-CD38 antibodies and lenalidomide. Most participants had difficult-to-treat disease, with over 90% not responding to their most recent therapy. 

In MajesTEC-9, Tecvayli was compared with standard treatment options: pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Tecvayli significantly improved outcomes, reducing the risk of disease worsening or death by 71% and the risk of death by 40%. The safety profile was manageable and consistent with what is already known about the drug, with no new safety concerns identified. 

These findings build on results from the Phase 3 MajesTEC-3 study, published in The New England Journal of Medicine, which showed significant improvements in progression-free survival (PFS) and overall survival (OS) when Tecvayli  was combined with Darzalex Faspro® (daratumumab and hyaluronidase-fihj) in patients who were new to or still responsive to anti-CD38 therapy. 

Together, MajesTEC-3 and MajesTEC-9 address different stages of multiple myeloma, showing the potential of Tecvayli to benefit patients earlier in their disease journey as well as those with hard-to-treat disease.  
 

Based on the strength of the MajesTEC-9 results, an independent monitoring committee recommended unblinding the study. Full results will be presented at a future medical meeting and shared with global health authorities. 
 

Reference: 
TECVAYLI® monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide, (https://www.jnj.com/media-center/press-releases/tecvayli-monotherapy-demonstrates-superior-progression-free-and-overall-survival-versus-standard-of-care-as-early-as-first-relapse-in-patients-with-multiple-myeloma-predominantly-refractory-to-anti-cd38-therapy-and-lenalidomide) Johnson & Johnson press release, January 14, 2026. 
 

U.S. Food and Drug Administration (FDA) 

FDA clears Investigational New Drug (IND) application for in vivo BCMA CAR T, KLN-1010 as treatment for RRMM 

On Wednesday, January 7, Kelonia Therapeutics announced via press release (https://www.businesswire.com/news/home/20260107179212/en/Kelonia-Therapeutics-Announces-FDA-Clearance-of-Investigational-New-Drug-IND-Application-for-KLN-1010-an-in-vivo-BCMA-CAR-T-Therapy-for-Relapsed-and-Refractory-Multiple-Myeloma) that the U.S. Food and Drug Administration (FDA) has given clearance to the Investigational New Drug (IND) application for KLN-1010 — an in vivo B-cell maturation antigen (BCMA) CAR T therapy for the treatment of relapsed/refractory multiple myeloma. 

According to Kelonia Therapeutics, this “represents the second regulatory clearance for KLN-1010 and enables the first multi-center clinical trial in the U.S. for an anti-BCMA in vivo CAR T program.” 

KLN-1010 is a new type of gene therapy that is designed to help a patient’s own body make anti-BCMA CAR-T cells after a single infusion. Unlike traditional CAR-T therapy, it does not require chemotherapy beforehand or the collection and custom manufacturing of a patient’s T cells. 

The FDA’s clearance of the IND application allows Kelonia to expand its ongoing Phase 1 clinical trial (called inMMyCAR™), which is already enrolling patients in Australia, to additional clinical sites in the United States. 
 
Reference: 
Kelonia Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application for KLN-1010, an in vivo BCMA CAR-T Therapy for Relapsed and Refractory Multiple Myeloma (https://www.businesswire.com/news/home/20260107179212/en/Kelonia-Therapeutics-Announces-FDA-Clearance-of-Investigational-New-Drug-IND-Application-for-KLN-1010-an-in-vivo-BCMA-CAR-T-Therapy-for-Relapsed-and-Refractory-Multiple-Myeloma), Kelonia Therapeutics press release, January 7, 2026. 
 
 

FDA releases draft guidance for MRD and CR as endpoints to support accelerated approval for myeloma drugs 
 

On Tuesday, January 20, a draft guidance was released by the U.S. Food and Drug Administration (FDA) on how to use measurable/minimal residual disease (MRD) and complete response (CR) as endpoints in clinical trials for multiple myeloma drugs seeking accelerated approval. 
 
The FDA noted that many earlier accelerated approvals relied on overall response rate (ORR), but response rates in multiple myeloma are now already very high. This makes it harder for new trials to show meaningful improvements without enrolling much larger numbers of patients. As a result, the FDA recognized the need for more sensitive measures of treatment effectiveness, such as MRD. 
 
“Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval,” explains how clinical trials can be designed to use these measures to help bring promising treatments to patients more quickly. 
 
Based on the guidance, MRD is defined as the absence of detectable cancer cells in the bone marrow (or MRD negativity) among patients who have already achieved a complete response. Flow cytometry or next-generation sequencing (NGS) are used to measure MRD.  

The definition of complete response includes both complete response and stringent complete response, which are established categories used to describe deep levels of disease control in multiple myeloma. 
 
The use of MRD as an endpoint for accelerated approval in multiple myeloma was unanimously endorsed by the FDA’s Oncology Drug Advisory Committee (ODAC) in April 2024 (https://www.myeloma.org/news-events/multiple-myeloma-news/historic-turning-point-myeloma-odac-unanimously-votes-favor-mrd-testing), following an FDA analysis showing a strong relationship between MRD status and long-term patient outcomes. 
 
As it applies to accelerated approvals, drugs approved using MRD or complete response as primary endpoints must still confirm their clinical benefit in follow-up studies using standard outcomes such as progression-free survival or overall survival. 
 
The FDA is accepting public comments (https://www.regulations.gov/docket/FDA-2025-D-2616/document) on this draft guidance until March 23, 2026. 
 
References: 
Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval — Draft Guidance for Industry, January 2026 (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/minimal-residual-disease-and-complete-response-multiple-myeloma-use-endpoints-support-accelerated?utm_medium=email&utm_source=govdelivery), U.S. Food and Drug Administration Guidance Document. 
 
Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval; Draft Guidance for Industry; Availability. (https://www.regulations.gov/docket/FDA-2025-D-2616/document) Regulations.gov. ID FDA-2025-D-2616-0002. 
 
 

FDA grants fast track designation to trispecific antibody IBI3003 for the treatment of relapsed/refractory multiple myeloma 

On Monday, January 26, Innovent Biologics announced via press release (https://www.prnewswire.com/news-releases/innovent-announces-ibi3003-gprc5dbcmacd3-trispecific-antibody-receives-fast-track-designation-from-the-us-fda-for-relapsed-or-refractory-multiple-myeloma-302669853.html#:~:text=The%20Fast%20Track%20Designation%20granted,clinical%20development%20and%20regulatory%20review.) that the U.S. Food and Drug Administration has granted fast track designation to anti-GPRC5D/BCMA/CD3 tri-specific antibody IBI3003 as treatment for relapsed/refractory multiple myeloma (RRMM).  

According to Innovent, “this designation applies to the treatment of relapsed or refractory multiple myeloma, (R/R MM) in patients who have received four or more lines of previous anti-myeloma therapies, that include at least a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody.” 
 
IBI3003 is an investigational cancer medicine discovered and developed using Innovent’s Sanbody® platform, with its development progressing globally. IBI3003 is currently being studied in a Phase 1/2 clinical trial for RRMM patients in China and Australia, with a Phase 1/2 trial in the United States planned to begin soon. 

Early clinical results presented at ASH 2025 showed IBI3003 had a generally manageable safety profile and promising signs of efficacy in patients whose disease had progressed after two or more prior lines of therapy. 

The FDA's Fast Track Designation program is designed to speed the development and review of treatments for serious diseases with unmet medical needs through closer interaction with the FDA. 
 
Reference:  
Innovent Announces IBI3003 (GPRC5D/BCMA/CD3 Trispecific Antibody) Receives Fast Track Designation from the U.S. FDA for Relapsed or Refractory Multiple Myeloma (https://www.prnewswire.com/news-releases/innovent-announces-ibi3003-gprc5dbcmacd3-trispecific-antibody-receives-fast-track-designation-from-the-us-fda-for-relapsed-or-refractory-multiple-myeloma-302669853.html#:~:text=The%20Fast%20Track%20Designation%20granted,clinical%20development%20and%20regulatory%20review.), Innovent Biologics, Inc. Press release, January 26, 2026. 

FDA approves Darzalex Faspro in combination with VRd for the treatment of transplant-ineligible newly diagnosed myeloma
 

On Tuesday, January 27, the U.S. Food and Drug Administration (FDA) approved Darzalex Faspro (daratumumab and hyaluronidase-fihj)  in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of “adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).”

Efficacy was based on the results of the CEPHEUS study — an open-label, randomized clinical trial in people with newly diagnosed multiple myeloma who were not eligible for autologous stem cell transplant (ASCT) or chose not to receive ASCT as their first treatment.  

However, the benefit of Darzalex Faspro-VRd has not been established specifically in patients who refused ASCT as initial therapy.

A total of 395 patients were enrolled, with 197 patients receiving Darzalex Faspro plus VRd and 198 patients receiving VRd alone.  

Main results 
The major efficacy outcomes measured were overall minimal residual disease (MRD) negativity rate, and progression-free survival (PFS), assessed by an independent review committee (IRC) using the International Myeloma Working Group (IMWG) criteria.

Results showed:

• MRD negativity in 52.3% of patients treated with Darzalex Faspro-VRd, compared with 34.8% with VRd alone (p = 0.0005) 
• The PFS hazard ratio was 0.60 [95% CI: 0.41, 0.88]; p-value 0.0078].

Safety information 
The prescribing information includes warnings and precautions for:

• Hypersensitivity and other administration reactions 
• Infections 
• Neutropenia 
• Thrombocytopenia 
• Embryo-fetal toxicity interference with cross-matching and red blood cell antibody screening 
• Cardiac toxicity in patients with light chain (AL) amyloidosis

Dosing 
The recommended dose of Darzalex Faspro is 1,800 mg/30,000 units (1,800 mg daratumumab with 30,000 units hyaluronidase). Dosing details for the other drugs in the regimen are provided in their prescribing information.

Full prescribing information for Darzalex Faspro will be posted on Drugs@FDA. (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm)

Reference: 
FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-newly?utm_source=chatgpt.com), Resources for Information on Approved Drugs, U.S. Food and Drug Administration. January 27, 2026. 

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.  (https://www.myeloma.org/news-events/multiple-myeloma-news)