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.

 

The month of July is especially notable—with myeloma drug approvals for Darzalex (daratumumab) in the European Union (EU); for Blenrep (belantamab mafodotin) in Canada and the EU; for Sarclisa (isatuximab-irfc) in the EU; for Xpovio (selinexor) in China; an accelerated approval for Lynozyfic (linvoseltamab-gcpt), and an orphan drug designation for SAR446523 (a GPRC5D monoclonal antibody) from the U.S. FDA. Additionally, an extended review period has been announced by the FDA for Blenrep’s Biologics License Application (BLA), following the ODAC review on July 17. 
 

 

Guidelines  
 

EHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma — Nature Reviews Clinical Oncology (July 2025) 
 

Summary 
In 2021, the European Hematology Association (EHA) published its Clinical Practical Guidelines for the treatment of patients with smoldering multiple myeloma (SMM) and multiple myeloma (MM). Since then, there have been major updates. A novel international staging system (R2-ISS) was developed by EHA, along with the European Society for Medical Oncology, to stage the disease more accurately. New prognostic tools have also been on the rise, including minimal residual disease (MRD) and mass spectrometry—used to assess monoclonal protein in the blood.  
 
Additionally, 14 novel treatments have been approved by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). Because of these new developments, a multidisciplinary group of experts from EHA and the European Myeloma Network (EMN) have updated the evidence-based guidelines and revised their recommendations to help doctors improve their clinical practice and choose the best treatments (along with guidance in using established drugs or newer immunotherapies) for newly diagnosed and relapsed myeloma patients.   
 
The guidelines also suggest early treatment for some smoldering myeloma cases and offer advice on managing myeloma-related adverse events and complications: bone disease, kidney problems, infections, and side effects from immune-based therapies. 
 
EHA and EMN brought together a group of experts from across Europe, who carefully reviewed all important myeloma research published between January 2021 and May 2025. This included clinical trials, medical studies, and expert reviews. 
 
The team followed a grading system to rate the strength of the evidence behind each recommendation. When the research wasn’t clear, the experts discussed and agreed on what to recommend. 
 
The guidelines were reviewed and approved by both the EHA and EMN. They include treatments approved in Europe or the U.S., or those studied in large official trials. Treatments that showed some benefit in smaller studies are mentioned but not formally recommended. 
 
Why these guidelines matter 
Experts have updated the criteria used to identify high-risk multiple myeloma. New tools and tests (such as circulating plasma cells, mass spectrometry, and gene expression profiling) are being developed to help better predict how the disease will behave and how well treatments work. 
 
Other updates: 

• Urine tests are no longer routinely needed during follow-up, except at diagnosis and relapse, to rule out related diseases. 
• Blood tests (like serum free light chains) are now preferred over 24-hour urine collection for monitoring the disease. 

 
Myeloma care is moving toward more precise, less invasive tools to monitor the disease and guide treatment decisions. 
 
 
Reference: 
Dimopoulos, M.A., Terpos, E., Boccadoro, M. et al. EHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma. Nat Rev Clin Oncol (2025). https://doi.org/10.1038/s41571-025-01041-x  
 
 

Research 

 

Immunological consequences of CAR T-cell therapy: an analysis of infections complications and immune reconstitution — Blood Advances (June 2025) 
 

What is the purpose of this study? 
CAR T-cell therapy works well in treating tough cases of B-cell cancers like diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). However, this treatment can seriously weaken the immune system, especially B cells and CD4+ T cells, which take a long time to recover. 
 
In this study, 52 patients were followed for one year after treatment. The first 30 days saw the highest risk for infections — mainly bacterial. After that, the risk declined but viral infections became more common. 
 
Patients who developed cytokine release syndrome (CRS) were more likely to get infections later. 
 
These results show the need for careful monitoring and preventive care to protect patients from infections and help their immune systems recover after CAR T-cell therapy. 
 
How was the study conducted? 
This retrospective unicentric observational study looked at 52 patients— 42 with relapsed/refractory diffuse large B-cell lymphoma (RR DLBCL); and 10 with relapsed/refractory multiple myeloma (RRMM), who received CAR T-cell therapy in one hospital between May 2019 and August 2023. The study was approved by an ethics committee and followed proper guidelines. 
 
Researchers collected data from medical records to track immune system recovery over a year, as well as infections (type of infection, when it started, and what caused it). Follow-ups with patients were done for up to a year, except for those who relapsed or developed another type of cancer. Some patients received medications to help boost immune cells or antibodies — this was included in the analysis. 

What were the key findings of the study? 

• Bacterial infections were most common in the first 30 days after CAR T-cell therapy. 
• Later infections were more often viral. 
• Patients with multiple myeloma had more infections than those with lymphoma. 
• Recovery of important immune cells (CD4+ T cells and B cells) was slow or incomplete, making patients more vulnerable to infections. 
• Severe cytokine release syndrome (CRS) increased the risk of later infections. 
• Infections are a major cause of death after CAR T-cell therapy, especially in patients whose cancer does not return. 

 
Limitations: 

• This study was small and done at only one hospital, so its results may not apply to everyone. 
• Only 10 patients had multiple myeloma, so comparisons are limited. 

 
Reference: 
Andreas Riedel, Laurent Phely, et al. Immunological consequences of CAR T-cell therapy: an analysis of infectious complications and immune reconstitution. Blood Adv 2025; 9 (13): 3149–3158. doi: https://doi.org/10.1182/bloodadvances.2024015346 
 
 

Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma — Blood (July 2025) 
 

What is the purpose of this study? 
This study looked at how well the CAR-T cell therapy idecabtagene vicleucel (ide-cel) works in real-world patients with relapsed or refractory multiple myeloma (RRMM). 
 
Since clinical trials only include certain patients who meet strict requirements, this study aimed to see how safe and effective standard treatment with ide-cel (brand name Abecma®) is for patients in real-life settings. 
 
How was the study conducted? 
Unlike clinical trials that include only very specific patients, this study included a broader group of 821 patients, with 77% having serious medical conditions. The average age was 66, and about a third were 70 or older. The group also included 15% Black and 7% Hispanic patients. 
 
What were the key findings of the study? 

• Safety and effectiveness of ide-cel in the real world were similar to the results from the KarMMa trial, even though: 77% of patients had serious health conditions; most had tried an average of 7 previous treatments; and some had already received other BCMA-targeted therapies. 
• 73% of patients responded to ide-cel; 26% had a complete response; the average time for progression-free survival was 8.8 months; the average overall survival was 15.6 months. 
• Using bendamustine instead of the usual chemo drugs before CAR-T (due to drug shortages) led to worse outcomes—only 3.9 months progression-free survival vs. 9.1 months with standard chemo. 
• People who had high-risk genetics, poor overall health, or advanced disease stages had worse outcomes. 
• Factors like being female, aged 70+, and low platelets increased the risk of severe side effects. 
• Patients who had better disease control (partial or very good partial responses) before receiving ide-cel did better after treatment. 
• People with less aggressive disease, fewer blood count problems, and who got CAR-T therapy sooner after diagnosis tended to have better outcomes. 
• Older adults (70+) did well, likely because only healthier seniors were selected for CAR-T therapy. 

 

What are the side effects? 

• Cytokine release syndrome (CRS) occurred in 80% of patients, but only 3% were severe. 
• 28% had nerve-related issues (ICANS), with 5% being serious. 
• No patient developed Parkinsonism, a rare side effect seen in other CAR-T therapies. 
• 45% of patients had significant infections. 
•  6% died from treatment-related causes, similar to clinical trial results. 

 
Why this study matters 


This is the largest real-world study of ide-cel for RRMM. It shows that the treatment is effective and relatively safe. 
 
Ide-cel is a promising and effective treatment for a wide range of real-world multiple myeloma patients, including those who wouldn’t have qualified for earlier clinical trials. It remains a strong option for people with advanced disease, though careful monitoring is needed, especially in patients at higher risk for side effects. 
 
Reference: 
Surbhi Sidana, Nausheen Ahmed, et al. Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma. Blood 2025; 146 (2): 167–177. doi: https://doi.org/10.1182/blood.2024026216 
 
 

Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma — Blood Advances (July 2025) 
 

Summary 
Researchers studied 10 heavily treated myeloma patients who had already been treated with one type of CAR-T therapy targeting B-cell maturation antigen (BCMA). After relapsing, they were given a second CAR-T therapy that also targeted BCMA. 
 

What is the purpose of this study? 
This study is the largest real-world look at using two different FDA-approved BCMA-targeted CAR-T cell therapies, one after the other, in patients with relapsed or refractory multiple myeloma (RRMM). The goal was to understand if this approach is safe and effective, and to find out who might benefit most from it. 
 
 

Key points: 

• Using a second BCMA CAR-T treatment after the first one stopped working was safe and effective. 
• All patients responded well to the second treatment, with 60% showing no signs of cancer at a very sensitive level. 
• Patients who had a longer-lasting response to the first CAR T therapy were more likely to do well on the second one. 
• Serious side effects did not increase with the second treatment. 
• Only one patient lost the BCMA protein, which is needed for CAR T to work. 
• This approach may not work well for patients who relapse quickly after the second CAR-T treatment. 
• Patients who relapsed after cilta-cel had poor outcomes. Some were treated with BiTEs (bispecific antibodies) like talquetamab (brand name Talvey®), but most didn’t respond—possibly due to T-cell fatigue from previous treatments. 

 
Results revealed: 

• Patients first received ide-cel (Abecma®) and then cilta-cel (Carvykti®) as a second CAR T therapy. 
• Strong responses were seen with cilta-cel, similar to when it was used as a first treatment. 
• Patients who had longer responses to ide-cel were more likely to do well with cilta-cel. 
• Side effects were manageable, and most patients kept the BCMA protein needed for the CAR-T to work. 
• Re-treating patients with the same CAR-T therapy (like a second dose of cilta-cel) usually fails. 
• Using a different CAR-T product, like switching from ide-cel to cilta-cel, seems to offer better results. 
• Ide-cel and cilta-cel target the same BCMA protein but are built slightly different. 
• These differences may help overcome some forms of resistance, but short responses to ide-cel often lead to short responses to cilta-cel, suggesting other reasons for resistance, like T-cell exhaustion or a hostile tumor environment. 

 
Limitations of the study 
This was a small, retrospective study with limited follow-up and no detailed lab testing to understand resistance better. 
 

Why this study matters 
Sequential CAR-T therapy (ide-cel followed by cilta-cel) is a promising option, especially for patients who had a long remission after the first CAR T (over 12 months); and for patients with controlled disease at the time of the second infusion. This study supports sequential CAR-T therapy as safe and effective, especially if the first treatment works well for a while. 
 
Reference: 
Tim Richardson, Udo Holtick, Jan Hendrik Frenking, et al.  Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma. Blood Adv 2025; bloodadvances.2025016712. doi: https://doi.org/10.1182/bloodadvances.2025016712 
 
 
 

Teclistamab for patients with heavily pretreated relapsed/refractory multiple myeloma and renal impairment — Blood Advances (July 2025) 
 

Summary 
This study looked at how well the bispecific antibody teclistamab (brand name Tecvayli®) works in patients with relapsed or refractory multiple myeloma (RRMM) who also have kidney problems/renal impairment. These patients are often left out of clinical trials, so doctors have limited data on how safe or effective teclistamab is for them. 
 
A total of 384 patients received teclistamab. 81 patients had kidney impairment (45 with severe kidney problems; 18 on dialysis). These patients were generally older and had received more past treatments than those with normal kidney function. 

Key findings: 

• Teclistamab is safe, even for patients with severe kidney problems or those on dialysis. 
• Side effects like cytokine release syndrome (CRS) and neurotoxicity (ICANS) were similar between those with and without kidney issues. Most cases were mild to moderate and treatable. 
• Short-term blood issues like anemia and low platelets were more common in patients with RI, possibly because they received more treatments in the past. 
• Infection rates were not worse in patients with kidney issues. Serious infections were similar in both groups. 
• Response rates were similar between patients with and without kidney problems, with about half of patients responding to treatment. 
• Survival outcomes were also similar, even in patients with severe kidney problems or those on dialysis. 
• Some patients even saw improvements in kidney function after starting teclistamab. 
• Kidney function usually did not get worse, unless the cancer itself progressed. 

 
Why this study matters 
This is the largest real-world study so far, looking at teclistamab in patients with kidney problems. Previous reports only looked at a few patients; this study helps fill in the gaps. It shows that doctors can safely offer teclistamab to more patients, even those typically excluded from clinical trials. Teclistamab works well and is safe for patients with kidney problems, including those on dialysis. These patients should be included in future clinical trials so that new treatments can become available to a wider group. 
 
Reference: 
Danai Dima, Aimaz Afrough, Utkarsh Goel, et al. Teclistamab for patients with heavily pretreated relapsed/refractory multiple myeloma and renal impairment. Blood Adv 2025; 9 (14): 3408–3417. doi: https://doi.org/10.1182/bloodadvances.2025016059 
 
 

Immune Alterations in Myeloma Evolution and Outcomes: Quo Vadis? — Blood (July 2025, Review) 
 

Summary 
This review article discusses multiple myeloma and its early form — monoclonal gammopathy of undetermined significance (MGUS), which are linked to changes in the aging immune system. MGUS is common in older adults, but only about 1% of people with MGUS progress to myeloma each year. 
 
The body’s immune system can recognize and respond to MGUS, and studies in early myeloma show both parts of the immune system (innate and adaptive) try to keep it in check. Research has found that people with MGUS already show signs of immune aging, even before the disease progresses. 
 
As myeloma develops, it changes how immune cells work and grow in different areas of the bone marrow. Both cancer cells and their surrounding environment weaken the immune system, allowing the cancer to spread more easily and increasing the risk of infections. 
 
Each patient’s immune response is different; these differences can affect how well immune-based treatments work. More research is needed to understand how changes in the immune system affect treatments and outcomes.  
 
Key takeaways:

• Myeloma starts in the immune system; immune changes begin early, even in MGUS. 
• Aging, genetics, and inflammation all play roles in how MGUS progresses. 
• Some people’s immune systems fight better 
• Scientists recommend adding immune system markers to better monitor and guide treatment, and improve long-term results 
• Protecting or improving immune function may help prevent myeloma or improve treatment outcomes. 

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

Solitary but not simple—a call for precision risk stratification and individualized treatment in solitary plasmacytoma — Blood (July 2025, Editorial) 
 

What is solitary plasmacytoma? 


Solitary plasmacytoma is a rare type of cancer involving plasma cells. It usually appears as a single tumor in bone or soft tissue, without signs of widespread disease like in multiple myeloma. 
 
There are three main types: 

1. True solitary plasmacytoma – No cancer found in the bone marrow. 
2. Solitary plasmacytoma with minimal bone marrow involvement – A small number (<10%) of cancer cells in the bone marrow. 
3. Multiple myeloma – 10% or more cancer cells in the bone marrow. 

 
The type affects the outlook and treatment plan. Tumors in the bone (SBP) or outside the bone (extramedullary) may behave differently. Certain lab results (like abnormal proteins in the blood) can also signal a higher chance of the disease coming back or spreading. 
 
How is it treated? 
The main treatment is radiation therapy aimed at the tumor. In some small soft tissue tumors, surgery may remove SP completely.  Many patients stay in remission after treatment. In some cases, the cancer comes back or turns into multiple myeloma, often without warning. Doctors are still figuring out whether adding systemic treatment helps prevent this in patients with minimal marrow involvement. 
 
What new research tells us 
A recent study in France looked closely at the genetics of solitary bone plasmacytoma (SBP). They found: 

• A lot of genetic variation, meaning not all SBPs behave the same. 
• High-risk genetic changes (mutations)—especially in genes like KRAS, TP53, ATM, and ATR—were linked to faster progression to multiple myeloma. 
• One key mutation, KRAS, was a strong sign of higher risk. 
• Patients without these mutations had much better long-term outcomes (5-year progression-free survival of 79% vs. 36% for high-risk). 

The study also showed that patients who received extra systemic treatment did better, suggesting this might help prevent progression in high-risk patients. 
 
Why this matters 
Even though solitary plasmacytoma is usually treated locally (with radiation or surgery), genetic testing can help predict which patients are likely to relapse or develop multiple myeloma. This could lead to personalized treatment plans in the future. 
 
However, challenges remain. These cancers are rare, making large clinical trials difficult. There’s a need for more research, especially real-world studies, to guide the best treatments and follow-up care. 
 
Reference: 
Zanwar, S., Rajkumar, S.V. Solitary but not simple─a call for precision risk stratification and individualized treatment in solitary plasmacytoma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02701-8 

 
Evolution of clonal hematopoiesis on and off lenalidomide maintenance for multiple myeloma — Leukemia (July 2025, Letter) 
 

Summary 


Multiple myeloma makes up about 10% of all blood cancers. Treatments like stem cell transplants followed by lenalidomide (brand name Revlimid®) can help people live longer, but myeloma is still not curable. 
 
Over time, some patients develop a second primary hematologic malignancy (SPHM). These can include serious diseases like leukemia. About 7% of myeloma patients eventually develop one of these secondary cancers. 
 
Researchers have found that long-term use of lenalidomide may increase the risk of secondary cancers, especially certain types of leukemia. But doctors still don’t know how to predict who is most at risk. 

What is clonal hematopoiesis? 


Clonal hematopoiesis (CH) is a condition where small groups of stem cells carry genetic mutations—especially in genes like TP53. These mutations don’t cause cancer on their own, but they can grow over time and may eventually lead to leukemia or other blood cancers. CH is more common as people age and can be made worse by certain cancer treatments. 
 

What are the objectives of the study? 


To find out: 

1. If long-term lenalidomide treatment causes harmful CH mutations to grow 
2. If stopping lenalidomide reduces this risk 
3. If tracking these changes over time helps predict who will develop a second blood cancer 

 
How did they conduct the study? 

• Blood samples from 148 myeloma patients were compared to over 8,800 healthy people. 
• Some myeloma patients continued taking lenalidomide (from the ATLAS trial), while others stopped lenalidomide after being cancer-free (from the MRD2STOP trial). 
• Researchers tracked genetic mutations in blood over two years to look for CH and changes in those mutations over time. 

 
Key findings: 

• TP53 mutations (a high-risk CH type) were more common in myeloma patients than in healthy people. 
• These mutations expanded in patients who kept taking lenalidomide. Some of these patients went on to develop leukemia or other blood cancers. 
• In patients who stopped lenalidomide, harmful CH mutations were stable or even shrank in most cases. Only a small number had continued mutation growth, and only one developed blood cancer after stopping lenalidomide. 
• Mutations linked to normal aging (like DNMT3A) didn’t grow, showing the risk is specific to TP53 and similar genes. 

 
Why this study matters 
Lenalidomide helps control multiple myeloma, but it may also increase the risk of second cancers by promoting the growth of harmful CH mutations. Monitoring these mutations over time can help identify patients at risk. In some cases, discontinuing lenalidomide could lower this risk without affecting control over the myeloma. These findings could help shape safer, more personalized treatment plans and guide future research on cancer prevention. 
 
Reference: 
Cooperrider, J.H., Karaoglu, D.A., Kubicki, T. et al. Evolution of clonal hematopoiesis on and off lenalidomide maintenance for multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02707-2 
 
 

Clinical Trials 
 

In-vivo B-cell maturation antigen CAR T-cell therapy for relapsed or refractory multiple myeloma — The Lancet (July 2025, Correspondence) 
 

Summary 


CAR T-cell therapy is a powerful treatment for patients with relapsed/refractory multiple myeloma, especially when the disease has stopped responding to standard treatments. However, current CAR T therapy is costly, takes a long time, and involves complex steps like collecting the patient’s T cells and giving chemotherapy beforehand. 
 
Researchers tested the new therapy ESO-T01, which uses a virus to turn the patient’s own T cells into CAR T cells inside the body, instead of in a lab. This “in-vivo” approach skips the need for cell collection and chemotherapy, making the process easier and faster. 
 
How does ESO-T01 work? 

• ESO-T01 uses a specially designed virus to deliver genetic instructions to T cells to attack a protein called BCMA found on myeloma cells. 
• The virus was engineered to target only T cells, avoid being destroyed by the immune system, and reduce unwanted immune reactions. 
• It was given through a single IV infusion without the usual pre-treatment steps like chemotherapy. 

 
How was the study conducted? 
Four patients with advanced multiple myeloma (all had failed at least two previous treatments) were treated at a hospital in Wuhan, China. Each received a low dose of ESO-T01 between November 2024 and January 2025. All patients were monitored closely, especially in the first 48 hours. 
 

What are the side effects of ESO-T01? 

• All patients experienced early flu-like symptoms after infusion: chills, fever, low blood pressure, or low oxygen levels. These symptoms were managed with medications like steroids and resolved within 2 days. 
• Some patients had mild neurological symptoms like headaches or confusion, also controlled with treatment. 
• Blood tests showed temporary changes, including low white blood cells and inflammation, but most returned to normal later. 
• Two patients had lung infections that were treated with antibiotics. 
• No virus was found in the urine, saliva, or spinal fluid after treatment. 

 
Results revealed: 

• Patients 1 and 2 had a complete response, with all signs of cancer gone by 1–2 months. 
• Patients 3 and 4 showed partial responses, with a significant reduction in cancer and signs of disease control. 
• CAR T cells were found in the blood, bone marrow, and even in tumors 
• Patients with better T-cell types (like memory T cells) responded better to treatment. 
• No signs of the virus affecting other cells or causing long-term harm were seen, but this still needs further study. 

 
Why this study matters 


This is the first report of in-vivo CAR T-cell therapy being used in multiple myeloma patients. Even at low doses, ESO-T01 showed promising safety and effectiveness, especially for difficult-to-treat disease that had spread outside the bones. 
 
However, more patients and longer follow-up are needed to confirm these early results. If proven successful, this could become a faster, simpler, and more affordable option for CAR T-cell therapy. 
 
Reference: 
Xu J, Liu L, Parone P, Xie W, et al. In-vivo B-cell maturation antigen CAR T-cell therapy for relapsed or refractory multiple myeloma. Lancet. 2025 Jul 2:S0140-6736(25)01030-X. doi: 10.1016/S0140-6736(25)01030-X. 
 
 

Are we ready for an MRD-driven approach in multiple myeloma? — Blood (July 2025, Commentary) 
 

Summary 
In this commentary to the study, “Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial,” the authors discuss the MIDAS study and minimal residual disease (MRD) in newly diagnosed multiple myeloma (NDMM).  
 
The MIDAS study is testing a new, more personalized way to treat NDMM patients who are eligible for a stem cell transplant. 
 

What are the key points of the study? 

• In the first part of the study, about two-thirds of patients reached MRD negativity after receiving a four-drug combo: isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRd). 
• These results will be used to decide the next steps: 

                    - Patients who are MRD-negative may get less intensive treatment. 

                    - Patients who are still MRD-positive may need stronger treatment. 

What the findings revealed so far 

• The IsaKRd treatment led to the highest MRD negativity rate (63%) ever reported in a major trial. 
• Side effects were manageable, with low rates of heart issues and nerve damage. 
• The results support the use of carfilzomib-based treatments over older options, especially for younger or transplant-eligible patients. 
• MRD response may not fully reflect the cancer’s biology. Some high-risk myeloma patients may relapse even if they reach MRD negativity. 
• A single MRD test might not be enough; it’s better to track MRD over time. 
• The sensitivity of the MRD test matters—a deeper test (10⁻⁶) may predict outcomes better than the one used (10⁻⁵), but it’s more complex and costly. 

 

Why the MIDAS study matters 

• Current treatments for multiple myeloma follow a standard path (induction → transplant → maintenance) without adjusting based on how well each patient responds. 
• The MIDAS study wants to personalize treatment based on each patient’s response, especially using MRD status. 
• MRD predicts long-term outcomes like survival and relapse. 
• Using MRD allows doctors to adapt treatment—giving more when needed and less when not—while reducing side effects and treatment costs. 

 
The MIDAS study shows that MRD-based, personalized treatment is possible and may lead to better care for multiple myeloma patients. If confirmed with longer follow-up, this approach could become the new standard, helping doctors decide who needs more or less treatment based on how well they respond—not just on their diagnosis. 
 
Reference: 
Francesca Gay, Roberto Mina; Are we ready for an MRD-driven approach in multiple myeloma? Blood 2025; 146 (1): 2–4. doi: https://doi.org/10.1182/blood.2024028273 
 
 
 

Talquetamab improves patient-reported symptoms and health-related quality of life in relapsed or refractory multiple myeloma: Results from the phase 1/2 MonumenTAL-1 study — Cancer (July 2025) 
 

Summary 


Based on the results of the phase 1/2 MonumenTAL-1 study, the bispecific antibody talquetamab was approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have already tried at least three other treatments that didn’t work.  
 
It is the first approved drug that targets a specific protein (GPRC5D). Patients in the study received talquetamab every other week and were asked questions about quality of life—including pain, fatigue, emotional well-being, and overall health. 
 
Findings of the MonumenTAL-1 study revealed that RRMM patients who were treated with talquetamab (0.8 mg/kg every two weeks) reported feeling better over time in many areas, including: overall health; physical, emotional, and social functioning; less pain and fatigue; feeling that their disease was less severe. 
 
These improvements lasted throughout the study, even for patients who had already tried many other treatments. 
 
Side effects 

• Some patients felt worse during the first few cycles, especially with physical symptoms and fatigue. This may be due to the need for hospital stays during the early part of treatment or side effects like cytokine release syndrome (CRS). 
• Most patients began to feel better starting around cycle 3, and these improvements generally continued. 
• Many patients (over 70%) had taste changes like food tasting strange or metallic (called dysgeusia), which can affect appetite and cause weight loss. 
• Appetite loss peaked at cycle 3 but improved by cycle 15 and beyond. 
• Despite taste issues, most patients reported stable or improved appetite starting at cycle 5. 
• About one-third of patients lost significant weight early in treatment, but this usually stabilized by cycle 8 and then got better. 

 
Limitations 

• Fewer patients stayed in the study over time, so data from later cycles is more limited. 
• The study did not specifically track side effects related to GPRC5D (like taste changes) in detail, but future research will. 
• This was a single-arm study (no comparison group), and all patients had advanced disease, so results may not apply to all myeloma patients. 

 
Why this study matters 


Talquetamab helped improve symptoms and quality of life for patients with hard-to-treat myeloma, despite early side effects like fatigue or appetite loss. These findings support its use as a promising treatment option for patients who have already tried multiple other therapies. 
 
Reference: 
Schinke C, Touzeau C, Oriol A, et al. Talquetamab improves patient-reported symptoms and health-related quality of life in relapsed or refractory multiple myeloma: Results from the phase 1/2 MonumenTAL-1 study. Cancer. 2025;e35927. doi:10.1002/cncr.35927 
 
 

Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial— The Lancet Oncology (July 2025) 
 

Summary 


The DREAMM-7 study compared two treatment combinations for people with relapsed or refractory multiple myeloma. The two combinations were: 
    •    BVd: Belantamab mafodotin + bortezomib + dexamethasone 
    •    DVd: Daratumumab + bortezomib + dexamethasone 
 
An earlier analysis showed BVd helped patients live longer without their cancer getting worse. This updated report looks at overall survival (how long patients live) with more follow-up time. 
 
How was the study conducted? 
494 patients from 20 countries who already tried at least one previous treatment for myeloma took part in the study. These patients were randomly assigned to receive BVd or DVd. Treatment continued until the cancer got worse, serious side effects occurred, or patients chose to stop. 
 
Key results: 

• After about 3 years of follow-up, patients on BVd lived longer than those on DVd. 
• Median overall survival wasn’t reached for either group, but BVd clearly showed better survival chances. 
• Patients on BVd were more than twice as likely to have no detectable cancer after treatment (25% vs. 10%). 
• The duration of response was also longer for BVd (about 41 months vs. 18 months for DVd). 
• Even after switching to other treatments, patients who started on BVd still did better than those on DVd. 

 
Side effects: 

• The most common serious side effect was low platelets (56% with BVd vs. 35% with DVd), which can increase the risk of bleeding. 
• More people on BVd had serious side effects (53% vs. 38%), including pneumonia and infections. 
• A small number of patients died from treatment-related side effects (3% on BVd vs. 1% on DVd). 

 
Why this study matters 


The BVd treatment combo helped patients live longer and had better cancer-fighting results than DVd. While there were more side effects, the benefits suggest BVd could become a new standard treatment for patients with relapsed/refractory multiple myeloma. 
 
Reference: 
Vania Hungria, Paweł Robak, Marek Hus, et al. Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial, The Lancet Oncology, 2025, ISSN 1470-2045, https://doi.org/10.1016/S1470-2045(25)00330-4.  
 

 

Patient-reported outcomes with belantamab mafodotin, bortezomib, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): results from a phase 3, open-label, randomised controlled trial — The Lancet Haematology (July 2025) 
 

Summary 


This study looked at how two different treatment combinations affected patients with relapsed or refractory multiple myeloma. One group got belantamab mafodotin, bortezomib, and dexamethasone (BVd). The other group got daratumumab, bortezomib, and dexamethasone (DVd). Earlier results showed that the belantamab group lived longer without their cancer getting worse. This study focused on how the treatments affected patients’ quality of life. 
 
Why this study matters 


The combination BVd not only helped delay cancer progression but also maintained or improved patients' quality of life. These results suggest that this treatment could be a strong new option for patients with relapsed or refractory multiple myeloma. 
 
Reference: 
Vania Hungria, Marek Hus, ChengCheng Fu, et al. Patient-reported outcomes with belantamab mafodotin, bortezomib, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): results from a phase 3, open-label, randomised control, The Lancet Haematology, 2025, ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(25)00163-2. 
 

 

U.S. Food and Drug Administration (FDA) 
 

FDA eliminates REMS for autologous CAR T cell immunotherapies 

 

On Friday, June 27, The U.S. Food and Drug Administration (FDA) “eliminated the Risk Evaluation and Mitigation Strategies (REMS) for currently approved BCMA- and CD19-directed autologous chimeric antigen receptor CAR T cell immunotherapies," the FDA announced via a press release. 
 
What is REMS?  
REMS is an extra safety program the FDA can require for drugs with serious risks. It was originally used with CAR T therapies to make sure patients and providers could safely handle possible side effects like cytokine release syndrome (CRS) and neurological problems. 
 
Why was REMS removed for these CAR T therapies? 
After years of use and experience, the FDA now says that doctors and treatment centers have enough knowledge and tools to manage these side effects without the extra REMS rules. Key safety warnings are still clearly listed on the product labels. 
 
What does this mean for doctors and patients? 

• Hospitals and clinics no longer need special certification to give these treatments. 
• Easier access to CAR T therapies for patients. 
• Doctors can rely on standard safety labels and guides instead of following extra REMS requirements. 

 
However, the FDA will continue to monitor these therapies closely, including long-term safety studies and tracking any serious side effects. Drug companies are still required to follow up with patients for up to 15 years after treatment. 
 

Why the REMS removal matters  
Removing REMS means quicker access to potentially life-saving treatments, less administrative work for clinics, and more focus on patient care—without lowering safety standards. 
 

FDA accelerated approval: Lynozyfic™ (linvoseltamab-gcpt) for the treatment of RRMM 

 

On Wednesday, July 2, the FDA granted accelerated approval to Lynozyfic (linvoseltamab) for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) who have already received at least four prior treatments. The approval is based on results from the LINKER-MM1 study.  
 
Lynozyfic is a bispecific antibody, a type of drug that helps the immune system (specifically T cells) find and kill myeloma cancer cells. It targets two proteins: BCMA on cancer cells and CD3 on T cells. 
 
Among 80 patients who had already tried many other treatments: 70% responded to Lynozyfic, with 45% having complete response. Many patients responded quickly (within 1 month), with most responses lasting a long time—72% were still responding after 12 months. 
 

• Common side effects: muscle pain, fatigue, cough, diarrhea, nausea, pneumonia, and headaches. 
• Serious risks include: 

                - Cytokine Release Syndrome (CRS)  
                - Neurologic side effects, including a condition called ICANS
                - Risk of infections, low blood counts, liver issues, and harm to unborn babies

• Because of these risks, Lynozyfic is only available through a special safety program (REMS). 

 
How do patients get support? 
Regeneron offers a support program called Lynozyfic Surround™ with financial help and education. Patients can call 1-844-RGN-HEME for more information. 
 
 

FDA-ODAC votes against the use of belantamab mafodotin in triplet drug combinations for the treatment of RRMM  

 

On Thursday, July 17, the Oncologic Drugs Advisory Committee  (ODAC) of the U.S. Food and Drug Administration (FDA) held an advisory meeting to discuss BLA 761440—the application submitted by GlaxoSmithKline LLC, to use Blenrep (belantamab mafodotin) for the treatment of adults with relapsed/refractory multiple myeloma in combination with bortezomib and dexamethasone in patients who have received at least one prior line of therapy; and in combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide.   

The ODAC votes were based on considerations made on benefits vs risks. Committee members cast their votes to address these two questions: (1) Is the overall benefit-risk of belantamab mafodotin in combination with bortezomib and dexamethasone favorable at the proposed dosage in the proposed patient population? (Yes-3; No-5); and (2) Is the overall benefit-risk of belantamab mafodotin in combination with pomalidomide and dexamethasone favorable at the proposed dosage in the proposed patient population? (Yes-1; No-7). 
 

FDA extends review period for Blenrep BLA application; PDUFA action date moved to October 23 
 

On Wednesday, July 23, GSK announced via a press release that the FDA “has extended the review period for the Biologics License Application (BLA) for Blenrep (belantamab mafodotin-blmf) combinations for the treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy.” 
 
“The new Prescription Drug User Fee Act (PDUFA) action date is October 23, 2025, and provides the FDA with time to review additional information provided in support of the application,” said GSK. 

 

FDA orphan drug designation: SAR446523, a GPRC5D monoclonal antibody for the potential treatment of RRMM

 

On Wednesday, July 30, Sanofi announced via a press release that the FDA "has granted orphan drug designation to SAR446523, an IgG1-based Antibody-Dependent Cellular Cytotoxicity-enhanced (ADCC) monoclonal antibody (mAb) targeting G-protein coupled receptor family C group 5 member D (GPRC5D) for the potential treatment of patients with relapsed or refractory multiple myeloma (R/R MM). GPRC5D is highly expressed on plasma cells in MM patients, with low expression in healthy tissues. The FDA grants orphan drug designation to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the US."

However, "the safety and efficacy of SAR446523 has not been evaluated by any regulatory authority and is still under investigation," the press release notes.

According to Sanofi, "SAR446523 is an investigational IgG1-based mAb designed to target GPRC5D, which is highly expressed on plasma cells, with an engineered fragment crystallizable domain to enhance antibody dependent cell-mediated cytotoxicity. This innovative approach aims to improve the efficacy of treatment for MM, a rare and challenging cancer of plasma cells. Subcutaneous SAR446523 is currently being evaluated in an ongoing phase 1, first-in-human study in patients with R/R MM (clinical study identifier: NCT06630806). SAR4465523 originates from Sanofi Research in Vitry-sur-Seine, France."

 

Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA)  

 

EMA-CHMP gives positive qualification advice to i2TEAMM Novel Biomarker Procedure Application on the use of MRDnegCR as an intermediate early endpoint for conditional market approval in myeloma clinical trials 
 

On Wednesday, July 2, the International Myeloma Foundation (IMF) and the collaborative stakeholder group i2TEAMM (International Independent Team for Endpoint Approval of Myeloma MRD) announced the positive outcome of the i2TEAMM’s application on the use of minimal residual disease (MRD) as an early endpoint in myeloma clinical trials via a press release. 

In a scientific advice letter, the CHMP stated: “On 5/22/2025, the CHMP met and adopted the advice to be given to the applicant. CHMP agrees that, depending on the setting, a role for MRDnegCR as an endpoint to support (conditional) approval of a compound while the obligation to demonstrate long-term benefit remains, can be envisaged. This implies that the trials should be adequately planned to demonstrate a benefit in PFS or OS.” 

According to Nikhil Munshi MD, (Dana-Farber Cancer Institute — Boston, MA), a member of the i2TEAMM Executive Committee, the IMF Scientific Advisory Board, and the IMF Board of Directors, “[EMA-CHMP] recognizing MRD as a valid early endpoint brings us one step closer to delivering more timely, effective therapies to patients. This scientific advancement reflects the strength of global collaboration and data-driven progress in the field."  
 
“The new MRD endpoint will represent a sensitive early readout for conditional drug approval, allowing patients timely access to newer treatment options although trials should be adequately planned to demonstrate a benefit in PFS or OS," said Jesús San Miguel, MD, PhD (University of Navarra — Pamplona, Spain), who is also a member of the i2TEAMM Executive Committee and the IMF Scientific Advisory Board. 
 
 

European Hematology Association (EHA) and the European Myeloma Network (EMN) 

 

EHA-EMN include Pepaxti in new clinical practice guidelines for RRMM 
 

On Tuesday, July 8, Oncopeptides announced via a press release that its drug Pepaxti has been officially included in the European clinical guidelines for treating relapsed or refractory multiple myeloma (RRMM). 

Why this inclusion matters 

• Pepaxti is now recommended for RRMM patients whose disease has stopped responding to at least three main types of myeloma treatments (called triple-class refractory or exposed – TCR/TCE) and for patients who relapsed after immunotherapy, including CAR T or antibody-drug conjugates (ADCs), and have very limited options left. 
• This recommendation is based on strong clinical evidence (Level 1) and has received a Grade B rating, showing that experts consider it a reliable and valuable treatment option. 
• Among non-CAR T cell treatments, Pepaxti now holds the highest combination of clinical support and expert recommendation. 

 
What this means for RRMM patients in Europe 
This update to the EHA-EMN guidelines could lead to wider use of Pepaxti, giving more patients access to promising treatment when others fail. 
 
 

European Commission (EC) 
 

DARZALEX® (daratumumab) approved for the treatment of High-Risk SMM by EC 
 

On Wednesday, July 23, the European Commission approved DARZALEX® (daratumumab) in a subcutaneous form to treat patients with high-risk smoldering multiple myeloma (HR-SMM). This condition is an early, symptom-free stage of myeloma, but in high-risk patients, it often progresses to active disease within two years. The approval was based on the results of the phase 3 AQUILA study. 
 
“Until now, the absence of approved therapies for high-risk smoldering multiple myeloma has left clinicians with limited options beyond observation, despite evidence that 50 percent of this patient population progress to active multiple myeloma within two years. The approval of daratumumab offers the potential to change this trajectory. By intervening earlier in the disease course, we have a meaningful opportunity to delay or prevent progression to symptomatic disease, reduce irreversible end-organ damage and extend the window of improved patient outcomes,” said Prof. Meletios A. Dimopoulos, MD (Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine— Athens, Greece). 
 
According to Johnson & Johnson, "this milestone marks a critical advance in early intervention for multiple myeloma as the first authorized treatment, offering a new treatment paradigm for patients with high-risk smoldering disease.” To find out more, read Johnson & Johnson’s official press release.  
 
 

Health Canada 
 

BLENREP® (belantamab mafodotin) combinations approved for the treatment of RRMM in Canada 
 

On Wednesday, July 23, Health Canada approved Blenrep (belantamab mafodotin) to be used “in combination with bortezomib and dexamethasone, or in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including lenalidomide for the latter combination,” states GSK in a press release. 

Blenrep is the first and only approved anti-BCMA antibody-drug conjugate (ADC) for multiple myeloma in Canada. It works in a unique way to target and kill cancer cells. 

“As patients with multiple myeloma receive combination therapies at diagnosis, the availability of diverse treatment options like Blenrep is vital for prolonging remission and enhancing survival outcomes. This milestone represents a transformative step forward in the treatment landscape, empowering our community and reinforcing our commitment to making myeloma matter while driving progress toward a cure,” said Myeloma Canada CEO and IMF Board Member Martine Elias.  
 

European Union (EU) 
 

BLENREP® (belantamab mafodotin) combinations approved for the treatment of RRMM in EU 
 

On Thursday, July 24, the European Union (EU) approved Blenrep (belantamab mafodotin) for the treatment of adults with relapsed/refractory multiple myeloma “in combination with bortezomib plus dexamethasone (BVd) in patients who have received at least one prior therapy, and in combination with pomalidomide plus dexamethasone (BPd) in patients who have received at least one prior therapy including lenalidomide,” said GSK in a press release. 
 
“The approval is based on superior efficacy results demonstrated by Blenrep combinations in the pivotal DREAMM-7 and DREAMM-8 phase III trials in relapsed or refractory multiple myeloma. These include statistically significant and clinically meaningful progression-free survival (PFS) for Blenrep combinations versus triplet standard of care combinations in both trials and overall survival (OS) versus a daratumumab-based triplet in DREAMM-7. The safety and tolerability profiles of the Blenrep combinations were broadly consistent with the known profiles of the individual agents,” GSK further stated. 
 
According to DREAMM-7 Principal Investigator and IMF Scientific Advisory Board Member María-Victoria Mateos, MD, PhD, (University of Salamanca — Salamanca, Spain), “with the approval of Blenrep combinations in the EU, we now have additional tools in our efforts to keep patients in remission longer, maintain quality of life and extend survival. The robust efficacy supported by the DREAMM-7 and DREAMM-8 trials, together with manageable outpatient administration in academic and community settings, positions Blenrep combinations as a fundamentally differentiated treatment approach for multiple myeloma patients starting from first relapse.” 
 
 

SARCLISA® (isatuximab-irfc) approved for the treatment of transplant-eligible newly diagnosed multiple myeloma in EU 
 

On Friday, July 25, the European Union (EU) approved Sarclisa (isatuximab-irfc) to be used “in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the induction treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplant."
 
“The approval is based on results from part one of the two-part, double-randomized, German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study (clinical study identifier: NCT03617731), which was designed to independently assess the effects of Sarclisa during the induction and maintenance phases. Sarclisa-VRd demonstrated a deep and rapid response in transplant-eligible (TE) NDMM patients compared to VRd alone, reflected by a statistically significant minimal residual disease (MRD) negativity benefit at the end of the 18-week induction period, which was the primary endpoint of part one,” stated Sanofi in a press release. 
 
“The results are part of the growing body of clinical evidence supporting the use of Sarclisa in the front-line setting and reinforce the potential of Sarclisa-VRd when used prior to transplant. Data from part two, the maintenance portion of the study, are forthcoming. 
 
“With four approved indications globally, including two in the front-line setting, the approval further affirms Sarclisa as an established MM treatment option, reflecting Sanofi’s ambition to address critical unmet needs in MM care and make a meaningful difference in treatment outcomes at every stage of the disease,” Sanofi further stated. 
 

China National Medical Products Administration (NMPA) 
 

China’s NMPA approves XPOVIO® (selinexor) for the second-line treatment of multiple myeloma 

 

On Monday, July 28, China’s NMPA approved XPOVIO® (selinexor) “in combination with bortezomib and dexamethasone (XVd) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy, a new indication of Xpovio,” announced Antengene via a press release. 
 
“This approval for XPOVIO® in combination with bortezomib and dexamethasone (XVd) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy marks the third approved indication of the drug in China. Results from the BENCH study show that, compared to the Vd regimen (bortezomib in combination dexamethasone), the XVd regimen offers greater efficacy, a longer progression-free survival (PFS), a longer duration of response (DOR), a higher objective response rate (ORR), and a trend of prolonged overall survival (OS) in Chinese patients with RRMM who have received at least one prior therapy,” stated Antengene. 
 
Xpovio in combination with dexamethasone in patients with RRMM (one of the three approved indications of the drug) has already been included in China's National Reimbursement Drug List, notes the press release. 
 
For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.