October and November 2025: What’s New in Myeloma?
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.
In this week’s blog, read about the 35-year contributions of the Intergroupe Francophone du Myélome (IFM) through academic trials focused on high-dose therapy and autologous stem cell transplantation (ASCT).
Discover new developments in myeloma research: the PREVEMM risk score; circulating tumor cells by Next-Generation Flow (NGF) cytometry as a new prognostic biomarker for patients with asymptomatic monoclonal gammopathies; hypoalbuminemia as a new risk factor for progression in MGUS patients, and more.
Catch up on some of the latest in clinical trials, including patient-reported outcomes of the phase 3 open-label randomized controlled trial, DREAMM-8.
Learn more about the FDA approval for Darzalex Faspro® (daratumumab and hyaluronidase-fihj) as treatment for high-risk smoldering multiple myeloma (HR SMM).
Review
Molecular and immunological determinants of long-term survival in multiple myeloma — Blood Advances (October 2025)
Background
Long-term survival (living 10 years or more after diagnosis with only one line of treatment) is becoming more common in multiple myeloma, thanks to major advances in therapy.
These include proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, stem cell transplants, and new immune-based treatments like CAR T-cell therapy and bispecific antibodies.
However, only some patients achieve lasting remission. Research shows that both the tumor’s biology and the patient’s immune system play key roles in long-term disease control. Long-term survivors tend to have a healthier bone marrow immune environment, with stronger T-cell and natural killer (NK) cell activity and fewer immune-suppressing cells.
What is the purpose of this review?
This review highlights recent progress in myeloma treatment, especially new immunotherapy approaches that help some patients achieve long-term survival (LTS). It explains how the immune system and the bone marrow environment work together to keep the disease under control for many years. The review focuses on immunotherapy and immune-related biology, rather than traditional treatments like chemotherapy, proteasome inhibitors, or stem cell transplants.
Looking ahead
Future treatment aims to recreate this protective immune environment in more patients. This includes:
• Using genomic and immune profiling to personalize therapy.
• Targeting minimal residual disease (MRD) — the tiny amount of cancer that can remain after treatment — with sensitive tests and immune-based therapies.
• Enhancing or preserving immune function, especially during and after treatments like CAR-T therapy.
• Exploring new therapy targets (e.g., GPRC5D, FcRH5) and strategies that modify the bone marrow microenvironment.
Why does this review matter?
Ultimately, the goal is to move beyond disease control toward long-lasting remission or functional cures. By understanding what makes long-term survivors unique, researchers hope to design treatments that help many more people live longer and better with multiple myeloma.
Reference:
Khanmi Kasomva, Kritika Yadav, Siegfried Janz, Binod Dhakal, Sridhar Rao; Molecular and immunological determinants of long-term survival in multiple myeloma. Blood Adv 2025; 9 (20): 5134–5147. doi: https://doi.org/10.1182/bloodadvances.2025016829
35 years of academic trials focusing on high-dose therapy and autologous stem cell transplantation: the Intergroupe Francophone du Myélome (IFM) experience — Blood Cancer Journal (October 2025)
Background
Over the past 30 years, treatment for multiple myeloma has improved dramatically. Median survival has increased from about 5 years in the 1990s to over 15 years today. These improvements largely come from research led by the Intergroupe Francophone du Myélome (IFM), which developed and tested key treatment strategies for patients who can receive a stem cell transplant.
The IFM is a French research network that unites about 80 hospitals and clinics caring for patients with myeloma. Since its creation in 1990, IFM has coordinated nationwide clinical trials quickly and efficiently, helping to improve treatments for myeloma patients in France and beyond.
What the IFM has done so far
1. Establishing stem cell transplant as standard care
Early IFM trials proved that high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) works better than traditional chemotherapy, nearly doubling survival rates. This approach became the standard for younger, fit patients.
2. Improving transplant strategies
The IFM found that:
• Two (tandem) transplants benefited patients with high-risk disease or incomplete responses.
• Melphalan 200 mg/m² (without radiation) was the most effective and safest pre-transplant conditioning treatment.
3. Tailoring treatment by risk
The IFM created one of the first risk-based treatment approaches, identifying two key poor-prognosis factors: high β2-microglobulin levels and chromosome 13 deletion.
• Standard-risk patients benefited from thalidomide maintenance, although side effects later led to using lenalidomide instead.
• High-risk patients did not benefit from adding an anti–IL-6 antibody or switching to donor transplants.
4. Maintenance therapy improves long-term outcomes
The IFM 2005-02 trial showed that lenalidomide maintenance after ASCT significantly prolongs remission, establishing it as the global standard. Long-term monitoring is needed due to a slightly higher risk of secondary cancers.
5. Better pre-transplant (induction) treatments
Earlier regimens (like VAD) were replaced by combinations including bortezomib (Velcade):
• Bortezomib + dexamethasone (Vd) increased deep response rates and became the new baseline regimen.
• Adding a third drug — thalidomide (VTd) or cyclophosphamide (VCd) — further improved results, with VTd preferred for most patients.
6. Combining modern drugs (VRd regimen)
The IFM 2009 trial confirmed that VRd plus ASCT led to longer remissions than VRD alone, although overall survival was similar. This established VRd + ASCT + lenalidomide maintenance as the backbone of treatment.
7. Quadruplet therapy with immunotherapy
Adding the antibody daratumumab to VTd (Dara-VTd) in the CASSIOPEIA trial significantly improved response rates, remission depth (MRD negativity), and survival. Dara-VTd is now a preferred frontline treatment.
8. Toward personalized, MRD-guided treatment
The ongoing MIDAS trial is testing whether therapy can be tailored based on minimal residual disease (MRD). Early results show deep responses using isatuximab-based quadruplets, but long-term results are still pending.
Future directions and conclusions
Over the years, IFM studies have answered major questions about how best to treat newly diagnosed, transplant-eligible patients — including the benefits of ASCT, the value of single versus double transplants, and the role of maintenance therapy. Each trial built upon the previous one, guiding international standards of care.
The IFM also leads cutting-edge research, using advanced genetic testing, imaging, and MRD assessments to personalize treatment. Following its recent MIDAS trial on MRD-guided therapy, IFM launched a new study in 2025 (the ElLen trial) to compare stem cell transplantation with bispecific antibody-based therapy as the next step in improving outcomes.
In summary, over the past 35 years, IFM’s 13 major clinical trials have transformed how multiple myeloma is treated—progressing from conventional chemotherapy to transplant-based care, then to modern targeted and immune therapies—helping patients live longer and better lives.
Reference:
Moreau, P., Hulin, C., Talbot, A. et al. 35 years of academic trials focusing on high-dose therapy and autologous stem cell transplantation: the Intergroupe Francophone du Myélome (IFM) experience. Blood Cancer J. 15, 177 (2025). https://doi.org/10.1038/s41408-025-01387-6
Bispecific antibodies in multiple myeloma: maximizing potential through rational combination therapies — Blood Reviews (October 2025)
Background
Bispecific antibodies are a new and powerful type of immunotherapy for multiple myeloma. They work by connecting immune T cells directly to myeloma cells, helping the immune system destroy cancer.
As of 2025, four bispecific antibodies have been approved for patients whose disease has returned or stopped responding to other treatments:
• teclistamab, elranatamab, and linvoseltamab (target BCMA × CD3)
• talquetamab (targets GPRC5D × CD3)
Other drugs, such as cevostamab (targeting FcRH5) and newer versions that bind differently, are still being studied.
While these treatments show strong results (response rates around 50–70%), some patients eventually develop resistance, often due to loss of the target protein or reduced T-cell activity. Researchers are testing combinations with other drugs (IMiDs, proteasome inhibitors, and checkpoint blockers) and exploring multi-target antibodies to overcome resistance.
What is the purpose of this review?
This review explores the latest advances in bispecific antibodies for multiple myeloma and summarizes current clinical trials. Its goal is to help unlock the full potential of these treatments as a key part of therapies that could potentially cure the disease.
Key safety points
• Cytokine release syndrome (CRS) is the main immune side effect.
• BCMA-targeted drugs can lower antibody levels, so monthly IV immunoglobulin (IVIG) is often needed.
• GPRC5D-targeted drugs can cause skin and nail issues but have fewer infections.
• Monitoring antigen loss helps guide future treatment choices (e.g., CAR-T eligibility).
Looking ahead
Bispecific antibodies are being tested as earlier treatments (even before transplant) in ongoing trials. They may offer a convenient, “off-the-shelf” alternative to CAR-T therapy, which is more complex and expensive. With better infection prevention and outpatient administration, these therapies could become more accessible and potentially curative for some patients.
Future research will focus on:
• Combining bispecific antibodies with other drugs to boost results
• Using them earlier in treatment to improve long-term outcomes
• Finding markers (like soluble BCMA) to predict response
• Determining the best treatment order with CAR-T and other myeloma drugs
Reference:
Xiang Zhou, Johannes M. Waldschmidt, Hermann Einsele, Bispecific antibodies in multiple myeloma: maximizing potential through rational combination therapies, Blood Reviews, 2025, 101342, ISSN 0268-960X, https://doi.org/10.1016/j.blre.2025.101342.
Research
Development of PREVEMM: A Venous Thromboembolism Risk Score for Newly Diagnosed Multiple Myeloma Patients — Clinical Lymphoma, Myeloma & Leukemia (October 2025)
Background
Blood clots (also called venous thromboembolism or VTE) are a serious and sometimes life-threatening complication in people newly diagnosed with multiple myeloma (NDMM), especially during the first year after diagnosis. Current tools used to predict which patients are most at risk are not very accurate.
What is the purpose of the study?
Researchers developed a new risk score, called PREVEMM, to better predict which newly diagnosed MM patients are most likely to develop blood clots.
How was the study conducted?
The study analyzed information from 225 myeloma patients treated at four hospitals between 2014 and 2019. Using a modern statistical method (LASSO), researchers identified key disease- and treatment-related factors that increase clotting risk.
Key findings
• 14% of patients developed blood clots within a year, most often pulmonary embolism (a clot in the lungs).
• The PREVEMM score correctly predicted clotting risk with 88% accuracy, far outperforming existing tools (which were only about 60% accurate).
• Seven key factors were linked to higher clotting risk:
1. Poor physical condition (ECOG score ≥1)
2. Advanced myeloma stage (high R-ISS)
3. Use of high-dose dexamethasone
4. High LDH levels (a marker of aggressive disease)
5. Immunoparesis (low levels of normal antibodies)
6. Spinal cord compression
7. Paralysis
Why this study matters
PREVEMM allows doctors to identify high-risk patients early—right at diagnosis—using routine clinical and lab information. This can help personalize clot-prevention strategies:
• High-risk patients could receive stronger or longer blood-thinning protection.
• Low-risk patients might safely avoid unnecessary anticoagulation and its bleeding risks.
Limitations
The study was done in a relatively small group from 2014–2019, so results need to be confirmed in larger, modern patient populations.
Conclusion
The PREVEMM score is a promising new tool that more accurately predicts blood clot risk in people with newly diagnosed multiple myeloma. It may help doctors tailor clot prevention to each patient, improving safety and outcomes.
Reference:
Martínez-Alfonzo I, Velasco-Rodríguez D, Mínguez-Paniagua P, Mahillo-Fernández I, Fernández-Cuezva L, Velasco-Valdazo A, Vidal-Laso R, Maqueda CF, Martín-Herrero S, Revilla N, González-Teomiro AC, Civeira-Marín M, Prieto E, Domingo-González A, Soto C, Calvo-Villas JM, Askari E, Llamas-Sillero P, Serrano-López J. Development of PREVEMM: A Venous Thromboembolism Risk Score for Newly Diagnosed Multiple Myeloma Patients. Clin Lymphoma Myeloma Leuk. 2025 Oct 10:S2152-2650(25)04244-2. doi: 10.1016/j.clml.2025.10.008.
Circulating tumor cells by Next Generation Flow Cytometry as a new prognostic biomarker for patients with asymptomatic monoclonal gammopathies — Blood Cancer Journal (October 2025, Correspondence)
Background
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are early, symptom-free stages that can develop into multiple myeloma. Most patients are monitored without treatment (“watch-and-wait”). Doctors use blood and bone marrow tests to estimate each patient’s risk of progression, but predicting who will develop active myeloma remains challenging.
What is the purpose of the study?
Researchers at Alexandra General Hospital studied 253 people diagnosed with MGUS or SMM since 2016. They looked for circulating tumor cells (CTCs)—abnormal plasma cells that escape from the bone marrow into the bloodstream—using a very sensitive test called Next Generation Flow cytometry (NGF). The goal was to see if the presence or amount of CTCs at diagnosis could predict which patients were more likely to develop active myeloma over time.
Key findings
• CTCs were found in 36% of all patients (22% of MGUS and 54% of SMM).
• Patients with detectable CTCs had higher disease activity markers (like abnormal protein levels in blood and bone marrow).
• After a median follow-up of 2 years, 23 patients developed active myeloma.
• The risk of progression was higher when CTCs were detected:
◦ 2-year progression rate: 10% with CTCs vs 7% without.
◦ In SMM, patients with CTCs were about three times more likely to progress to active disease.
• A small threshold amount (≥0.0014% CTCs) best identified those at higher risk.
What this means
CTCs in the blood may serve as a simple, non-invasive marker to help identify patients with smoldering myeloma who are more likely to develop symptoms. For now, this is an early finding—more follow-up and larger studies are needed to confirm whether CTC testing should be used routinely, especially for MGUS.
Why this study matters
• CTC testing could improve early detection of higher-risk patients using a blood test instead of a bone marrow biopsy.
• It may eventually help doctors tailor follow-up and treatment timing more precisely.
• For now, patients with MGUS or SMM should continue regular monitoring as advised by their care team.
Reference:
Kastritis, E., Malandrakis, P., Kostopoulos, I.V. et al. Circulating tumor cells by Next Generation Flow Cytometry as a new prognostic biomarker for patients with asymptomatic monoclonal gammopathies. Blood Cancer J. 15, 170 (2025). https://doi.org/10.1038/s41408-025-01369-8
Epidemiological landscape of early-onset multiple myeloma: global burden, temporal trends, cross-country inequality, and projections to 2045 — Hematology (October 2025)
What is the purpose of the study?
Multiple myeloma usually affects older adults, but it is increasingly being diagnosed in younger people under age 50 — called early-onset myeloma. This study examined how common early-onset myeloma is worldwide, how it has changed over time, and what may be driving these trends.
Key findings
• From 1990 to 2021, the number of early-onset MM cases and related deaths more than doubled globally.
• The increase was faster in younger patients than in those over 50.
• In 2021, for every 100,000 people worldwide:
◦ About 0.28 developed early-onset MM each year (incidence rate),
◦ 1 person was living with it (prevalence rate),
◦ and the disease caused 8.6 disability-adjusted life years (DALYs) — a measure combining illness and early death.
• Men had higher rates and faster growth of the disease than women.
• High-income countries had the highest burden, though the gap between rich and poor countries is slowly narrowing.
• Population growth was the main reason for the rising total burden.
• In wealthy countries, better healthcare and awareness helped slow or reduce MM-related deaths, while rates are still increasing in developing regions.
Possible reasons for the increase
• Higher obesity rates among younger adults may increase MM risk.
• Better diagnostic tools and awareness mean more cases are detected.
• Improved treatments (like stem cell transplants and new immune therapies) help patients live longer, increasing the number of people living with MM.
• Biological and social differences between men and women—such as hormone effects and occupational exposures—may partly explain the higher rates in men.
Future projections
• By 2045, early-onset MM cases and prevalence are expected to keep rising, especially in developing regions.
• Although death rates may decrease overall due to medical advances, the total number of affected young patients will likely continue to grow.
Why this matters
Early-onset MM poses unique challenges because younger patients often have families and work responsibilities. The study highlights the need for:
• Greater public health attention and research into causes and prevention,
• Targeted health policies to address regional and socioeconomic differences,
• Continued improvements in diagnosis, treatment, and support for younger patients.
Reference:
Zhang, H., Li, M., Zhao, L., Wang, L., & Geng, J. (2025). Epidemiological landscape of early-onset multiple myeloma: global burden, temporal trends, cross-country inequality, and projections to 2045. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2576308
Hypoalbuminemia: a new risk factor for progression in patients with monoclonal gammopathy of uncertain significance — Blood Cancer Journal (October 2025)
Background
Monoclonal gammopathy of undetermined significance (MGUS) is a common, usually harmless condition in which abnormal plasma cells make a small amount of M protein in the blood. However, a small percentage of patients each year progress to more serious diseases such as multiple myeloma. Doctors use various tests to estimate who is at higher risk, but predicting progression remains challenging.
What is the purpose of the study?
This study looked at whether low blood albumin levels (hypoalbuminemia, ≤3.5 g/dL)—a marker of inflammation—could help predict which MGUS patients are more likely to develop active disease.
How was the study conducted?
Researchers analyzed 838 patients with MGUS. About 8.5% had low albumin levels at diagnosis. These patients were typically older, more often male, and had worse kidney function and lower hemoglobin.
Key findings
• Low albumin and high M-protein (≥1.5 g/dL) were both independent predictors of disease progression.
• Patients with low albumin were up to five times more likely to progress to multiple myeloma or another related condition compared to those with normal albumin.
• Adding albumin levels to existing risk models (like the Mayo Clinic model) improved their accuracy.
◦ Patients with “intermediate risk” MGUS and low albumin had progression risks similar to “high-risk” patients.
What this means
A simple blood test measuring albumin could help doctors better identify which MGUS patients need closer monitoring. Since low albumin reflects inflammation, it may indicate a bone marrow environment that promotes disease progression.
Limitations
This was a retrospective, single-center study with relatively few patients showing low albumin, so results need confirmation in larger, independent groups. Other health issues could also lower albumin, which might affect the results.
Why this study matters
Low blood albumin is a new potential warning sign for MGUS patients at higher risk of developing multiple myeloma. Including albumin in existing risk models could lead to more personalized follow-up and earlier intervention for those most at risk.
Reference:
Alejo, E., González-Calle, V., Blázquez, P. et al. Hypoalbuminemia: a new risk factor for progression in patients with monoclonal gammopathy of uncertain significance. Blood Cancer J. 15, 179 (2025). https://doi.org/10.1038/s41408-025-01371-0
Improved survival in multiple myeloma following prior detection of precursor conditions: a nationwide real-world study — Blood Cancer Journal (October 2025, Correspondence)
Background
Multiple myeloma often develops slowly from MGUS and SMM. These early stages usually don’t cause symptoms, and treatment only begins once the disease progresses to active myeloma. However, it’s not clear whether finding and monitoring these early stages can actually improve survival.
What is the purpose of the study?
To explore this, researchers in Korea analyzed nationwide health insurance data covering nearly the entire population. They compared people who developed myeloma after being diagnosed with MGUS or SMM to those who were diagnosed with myeloma directly (“de novo” cases). The study included more than 17,000 patients diagnosed between 2009 and 2022.
Key findings
• Progression rates: About 7% of people with MGUS and 36% of those with SMM progressed to myeloma over 10 years.
• Survival: Patients who developed myeloma after a prior MGUS or SMM diagnosis lived significantly longer after starting MM treatment than those diagnosed with myeloma for the first time.
- MGUS-to-MM patients had about half the risk of death compared to de novo MM patients.
- SMM-to-MM patients also had better survival, though to a lesser degree.
• These benefits remained even after accounting for differences in age, health conditions, and treatments.
What this means
Early detection and monitoring of MGUS and SMM may help improve survival once myeloma develops, possibly because the disease is caught before it becomes more aggressive. The results were consistent with previous studies from the U.S. and Europe, but this is the first large study confirming the same pattern in an Asian population.
Limitations of the study
• The study used insurance data, so detailed lab results (like M-protein levels) were not available.
• Some early cases might have been misclassified due to reliance on medical billing codes.
• Although the researchers tried to correct for “lead-time bias” (the effect of simply finding disease earlier), this factor can’t be completely ruled out.
Why this study matters
Patients whose myeloma is detected through earlier stages like MGUS or SMM tend to live longer than those diagnosed at the active disease stage. While this doesn’t justify universal screening, it supports regular monitoring of people known to have MGUS or SMM, especially those at higher risk. Early identification and close follow-up could allow doctors to intervene at the right time and improve outcomes.
Reference:
Choi, S., Park, SS., Lee, C.H. et al. Improved survival in multiple myeloma following prior detection of precursor conditions: a nationwide real-world study. Blood Cancer J. 15, 185 (2025). https://doi.org/10.1038/s41408-025-01395-6
Improving predictive accuracy in multiple myeloma using a plasma cell profile derived from single-cell RNA sequencing — Haematologica (November 2025)
Background
Multiple myeloma is a cancer of plasma cells in the bone marrow. Because each patient’s cancer cells can be quite different, people respond differently to treatment. Current genetic tests can’t always predict which patients are at highest risk or will have poor outcomes.
How the study was conducted Researchers analyzed bone marrow samples from 12 newly diagnosed myeloma patients using advanced single-cell RNA sequencing. This technique studies the genes of individual cancer cells rather than averaging results across all cells. The goal was to find new biological markers that could identify patients with extremely high-risk myeloma—those who live less than two years after diagnosis.
Key findings
• Eight different groups (or “subclusters”) of myeloma cells were found within patients.
• One particular subgroup of cells was very aggressive, showing strong drug resistance, high chromosomal instability, and rapid growth.
• Patients with more of these aggressive cells had poorer survival outcomes.
• Seven key genes—LILRB4, CD74, TUBA1B, CCND2, HIST1H4C, ITGB7, and CRIP1—were highly active in these aggressive cells.
• A seven-gene signature based on these genes strongly predicted poor outcomes, even when other risk factors were considered.
New risk model
The researchers created a new system called the MR-ISS (Molecular Revised International Staging System). It combines the seven-gene signature with existing clinical and genetic factors to better identify ultra-high-risk patients. This model was successfully validated in several other patient groups.
Why this matters
• The new test may help doctors more accurately identify patients with the most aggressive type of MM.
• It could guide personalized treatment plans, helping doctors choose stronger or targeted therapies earlier for those at highest risk.
• The team also developed a simple lab test (digital PCR) to measure this seven-gene signature in routine clinical samples.
Additional insights
• The study showed that immune cells around the tumor (especially T cells) become exhausted and less effective, which may contribute to disease progression.
• Some of the seven genes, especially LILRB4, may help cancer cells escape the immune system and resist treatment.
• Blocking these genes or improving T-cell function could become new treatment strategies.
Looking ahead
This study identified a new seven-gene signature and developed a powerful risk-scoring tool that can pinpoint patients with very aggressive myeloma. It offers new hope for more accurate diagnosis, better treatment decisions, and development of therapies targeting both cancer cells and their surrounding immune environment.
Reference:
Liu L, Sun H, Feng F, Sun X, Ma J, Lv R, Yu T, Ye L, Li X, Yu Z, Zhang X, Jing H, Yao Y, Ma F, Qiu L, Hao M. Improving predictive accuracy in multiple myeloma using a plasma cell profile derived from single-cell RNA sequencing. Haematologica 2025;110(11):2726-2739; https://doi.org/10.3324/haematol.2025.287586.
LDHAL6B is a novel prognostic marker and promotes disease progression in multiple myeloma — Haematologica (November 2025, Letter to the Editor)
Background
Because myeloma varies greatly between patients, doctors use staging systems—like the International Staging System (ISS) and the Revised ISS (R-ISS)—to predict outcomes and guide treatment. However, these systems don’t always clearly identify which patients are at highest risk, especially since treatments have improved. Researchers are now looking for new biological markers to make risk assessment more accurate.
What is the purpose of the study?
This study identified a new gene, LDHAL6B, as a possible biomarker that can help refine MM risk prediction and support more personalized treatment decisions.
Key findings
• MM cells showed much higher levels of LDHAL6B compared to normal plasma cells.
• Among 158 MM patients studied, 43% had high LDHAL6B expression.
• Patients with high LDHAL6B had more advanced disease, worse kidney function, more bone damage, and more aggressive genetic abnormalities.
• These patients also responded less well to initial treatment and were less likely to achieve deep remission.
Impact on survival
Patients with high LDHAL6B levels had much shorter survival:
• Median progression-free survival (time before the disease worsened): 19 months vs. 81 months in those with low LDHAL6B.
• Median overall survival: 20 months vs. not yet reached (many still alive) in the low-expression group. Even after accounting for other risk factors, high LDHAL6B remained an independent predictor of poor outcome.
Improving risk prediction
The study also found that LDHAL6B provides valuable information beyond traditional lactate dehydrogenase (LDH) blood tests used in the R-ISS system. Many patients with normal LDH but high LDHAL6B still had poor outcomes.
The researchers developed a new risk model that combines LDHAL6B with existing high-risk factors (such as certain genetic changes and high LDH). This model better distinguished patients at low, intermediate, and high risk than the current R-ISS alone.
Laboratory findings
Further experiments showed that LDHAL6B helps myeloma cells grow, move, and invade other tissues. It also affects how cells process energy—similar to the “Warburg effect,” a process cancer cells use to fuel rapid growth.
Why this study matters
This is the first study showing that LDHAL6B is abnormally active in multiple myeloma and is linked to more aggressive disease and poorer survival. Including LDHAL6B in risk assessment could make MM staging more precise and help doctors identify patients who need more intensive or targeted treatment.
Reference:
Zuo L, Li Z, Cai L, Li Q, Fan F, Zhang B, Zhao F, Luo S, Zheng Y, Hu Y, Sun C. LDHAL6B is a novel prognostic marker and promotes disease progression in multiple myeloma. Haematologica 2025;110(11):2779-2785; https://doi.org/10.3324/haematol.2024.286835.
Healthcare resource utilization and costs in patients with multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, and were exposed to and discontinued lenalidomide in the United States — Journal of Medical Economics (November 2025)
Background
Multiple myeloma often relapses and becomes resistant to treatment. As patients go through several rounds of therapy, their care can become extremely costly. This study looked at healthcare use and costs for U.S. patients with MM who had already received one to three prior treatments.
Methods
Researchers reviewed insurance claims from adults with MM between 2011 and 2023. All patients had been treated with at least one proteasome inhibitor (PI) and one immunomodulatory drug (IMiD), had used and stopped lenalidomide, and started another therapy after 2018. Costs were measured from the start of the new treatment until follow-up ended.
Results
• Patients: 338 individuals, average age 61 years; most had not received a stem cell transplant after the study started.
• Average follow-up: 11.5 months.
• Total monthly healthcare costs: about $41,600 per patient.
• MM-related costs: about $39,700 per month (95% of total costs).
• Drug and infusion costs: the largest expense, making up 71% of MM-related costs (about $28,000/month).
• Results were similar even when including patients who later had a stem cell transplant.
Interpretation
Patients whose myeloma had stopped responding to lenalidomide faced a very high financial burden, mainly due to expensive medications and infusions. Similar studies show that as myeloma becomes more treatment-resistant, monthly costs rise sharply.
New and emerging therapies
Recently approved treatments such as monoclonal antibodies, CAR-T cell therapies, and bispecific antibodies offer new hope. These options can lead to longer remissions and may prove more cost-effective in the long term.
Limitations
• The study used insurance claims data, which may not capture all clinical details or apply to people without commercial insurance.
• Prescription data reflect medications filled, not necessarily taken.
• Results may not represent all myeloma patients in the U.S.
Conclusion
Patients with multiple myeloma who have had one to three prior treatments face very high healthcare costs, mostly driven by drug expenses. There is an urgent need for more effective and affordable therapies that can reduce both disease burden and treatment costs.
Reference:
Jagannath, S., Kharat, A., Chinaeke, E., Fu, A. Z., Perciavalle, M., Huo, S., & Qureshi, Z. P. (2025). Healthcare resource utilization and costs in patients with multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, and were exposed to and discontinued lenalidomide in the United States. Journal of Medical Economics, 1–13. https://doi.org/10.1080/13696998.2025.2583668
Pharmacokinetic and pharmacodynamic evaluation of alternative pomalidomide dosing regimens in the treatment of multiple myeloma — British Journal of Haematology (November 2025, Research Letter)
Background
Pomalidomide is a medicine used to treat multiple myeloma (MM) that has returned or stopped responding to other treatments. The standard dose (4 mg daily for 21 days out of 28) can cause side effects that sometimes require dose adjustments. Researchers wanted to find out if taking a lower daily dose (2 mg) or taking 4 mg every other day could work as well, with fewer side effects or lower costs.
How was the study conducted?
Twelve patients with relapsed/refractory MM took pomalidomide in three different ways:
1. 4 mg daily (21 days on, 7 off) – standard schedule
2. 2 mg daily (taken every day without breaks)
3. 4 mg every other day
Blood samples were analyzed to measure drug levels (pharmacokinetics, PK) and effects on immune cells (pharmacodynamics, PD).
Key findings
• The standard 4 mg daily dose achieved the strongest and most consistent drug levels in the blood and showed the greatest biological effect on immune cells.
• The 2 mg daily dose maintained adequate levels for most patients, with somewhat reduced immune activation but better tolerability.
• The 4 mg every-other-day schedule resulted in drug levels that were too low between doses, leading to weaker immune effects and likely less effectiveness.
Interpretation
• Keeping the drug level steady (as with daily dosing) is important for pomalidomide to work properly.
• The every-other-day schedule did not maintain these levels and therefore is not recommended, even though it might lower costs.
• The 2 mg daily dose may be a reasonable option for patients who experience side effects with the 4 mg dose.
Why this study matters
Daily pomalidomide dosing—either the standard 4 mg or a lower 2 mg dose—is most effective at maintaining drug activity and immune response. Taking 4 mg every other day is not effective enough. Future studies should continue to explore ways to personalize pomalidomide dosing to balance effectiveness, side effects, and cost.
Reference:
Seefat, M.R., Cucchi, D.G.J., van Boven, L., Durdu-Rayman, N., Groen, K., Levin, M.-.-D., de Heer, K., de Valk, B., Wester, R., van der Spek, E., Rentenaar, R., Korst, C.L.B.M., Quik, M., O'Neill, C.A., Tzortzi, P., Smits, F., Mathot, R., Heerma van Voss, M.R., van de Donk, N.W.C.J., Mutis, T., Bartelink, I.H. and Zweegman, S. (2025), Pharmacokinetic and pharmacodynamic evaluation of alternative pomalidomide dosing regimens in the treatment of multiple myeloma. Br J Haematol. https://doi.org/10.1111/bjh.70239
Proinflammatory bone marrow niches and neutrophil activation are associated with TIGIT expression in multiple myeloma — Annals of Hematology (November 2025)
What is the purpose of the study?
This study explored the role of a molecule called TIGIT in the bone marrow of patients newly diagnosed with multiple myeloma (MM). The goal was to find out how often TIGIT appears in bone marrow cells, what it means for disease severity, and whether it could be used as a biomarker (a sign of disease activity or risk) or a treatment target in the future.
What TIGIT is and why it matters
◦ TIGIT is a “brake” on the immune system that can weaken the body’s ability to fight cancer.
◦ When overexpressed, it helps cancer cells hide from immune attack.
How the study was done
◦ The researchers studied bone marrow samples from 25 newly diagnosed MM patients.
◦ They analyzed immune cells, cancer cells, and molecules linked to inflammation using advanced imaging and lab techniques.
What they found
TIGIT was present in 86% of samples, especially in patients with more aggressive disease, including:
▪ High-risk genetic changes
▪ Advanced disease stages
▪ High LDH levels (a marker of tissue damage)
TIGIT-positive samples showed signs of inflammation and immune suppression, including:
▪High levels of inflammatory molecules IL-6 and IL-8
▪Many neutrophils (a type of white blood cell) forming neutrophil extracellular traps (NETs) — sticky webs that can damage tissues and promote cancer growth. This inflammatory environment may help cancer cells grow and escape immune control.
New insights
◦ This is the first study to link TIGIT expression with neutrophil activity (NETosis) in multiple myeloma.
◦ All patients with smoldering (early-stage) myeloma also showed TIGIT expression and later needed treatment, suggesting it might predict disease progression.
Clinical significance
◦ TIGIT may serve as a marker of high-risk or aggressive myeloma.
◦ Blocking TIGIT (a strategy already being tested in other cancers) might restore immune function and improve treatment outcomes in MM.
Limitations and future directions
• The study included only a small number of patients, so larger studies are needed to confirm these results.
• Future research should test whether TIGIT levels predict treatment response and whether TIGIT-blocking drugs can benefit MM patients, possibly in early disease stages.
Conclusion
TIGIT appears to play an important role in how multiple myeloma evades the immune system and becomes more aggressive. It could serve as a warning sign for more severe disease and as a promising new treatment target to help strengthen immune responses against myeloma.
Reference:
Tomarchio, V., Arciprete, F., Di Cecca, M. et al. Proinflammatory bone marrow niches and neutrophil activation are associated with TIGIT expression in multiple myeloma. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06698-z
Therapeutic potential of PRMT1 as a critical survival dependency target in multiple myeloma — BMC Cancer (November 2025)
Background
Multiple myeloma affects plasma cells, which make antibodies. Although many treatments exist, the disease often comes back and becomes resistant to therapy. This study looked for new weak points (“vulnerabilities”) in myeloma cells that could be targeted with new drugs.
Key discovery
Using a genetic screening tool (CRISPR-Cas9) that tested nearly 200 genes related to DNA repair, researchers identified PRMT1 as a key protein that myeloma cells depend on to survive.
PRMT1 is an enzyme that modifies other proteins and helps control how genes are turned on and off. It is often overactive in cancers, including multiple myeloma, especially in patients whose disease has relapsed or stopped responding to treatment.
Findings of the study
• Blocking PRMT1 with a drug called GSK3368715 killed myeloma cells in the lab.
• The drug caused myeloma cells to stop dividing and halted their cell cycle, preventing growth.
• PRMT1 inhibition reduced the activity of genes and proteins involved in DNA repair and cell division.
• Instead of triggering standard cell death (like apoptosis), blocking PRMT1 seemed to cause an alternative type of cell damage known as ferroptosis, a process that destroys cells by increasing toxic iron and lipid levels.
• The results suggest PRMT1 is essential for myeloma cell survival and that drugs blocking it could make cancer cells more sensitive to other treatments.
Why this matters
PRMT1 is highly active in aggressive and treatment-resistant myeloma, making it an attractive new therapeutic target. The drug used in this study (GSK3368715) is already being tested in early human trials, supporting its potential for future clinical use.
Limitations and next steps
• The drug may also affect related enzymes (PRMT6, PRMT8), so more specific inhibitors are needed.
• Further studies are required to confirm how exactly PRMT1 inhibition kills myeloma cells.
• Combining PRMT1 inhibitors with existing myeloma treatments may offer stronger, longer-lasting responses.
Conclusion
This research identifies PRMT1 as a critical survival factor for multiple myeloma cells. Targeting PRMT1 with new drugs could open the door to more effective treatments, especially for patients with relapsed or drug-resistant disease.
Reference:
Hussain, T., Awasthi, S., Shahid, F. et al. Therapeutic potential of PRMT1 as a critical survival dependency target in multiple myeloma. BMC Cancer 25, 1704 (2025). https://doi.org/10.1186/s12885-025-15104-w
Outcomes of relapse after teclistamab therapy in multiple myeloma — Blood Cancer Journal (November 2025, Correspondence)
Background
Teclistamab is a bispecific antibody that helps the immune system attack multiple myeloma cells. It was approved in 2022 for patients whose myeloma has stopped responding to at least four prior treatments. Before drugs like teclistamab became available, these patients typically lived less than one year.
Study overview
Researchers at the University of Pennsylvania reviewed outcomes of 179 patients with advanced multiple myeloma treated with teclistamab between 2018 and 2024. All patients had disease resistant to the three main classes of myeloma drugs.
Key results
• Response rate (tumor shrinkage): 65%
• Median time before disease worsened (PFS): 9.8 months
• Median overall survival (OS): 18 months
• 1-year survival rate: 70%
However, most patients eventually relapsed (had the cancer return or worsen). After relapse:
• Median survival was only 6.6 months.
• Of 104 patients who relapsed, 67 received further (“salvage”) therapy.
• Responses to salvage therapy were modest (38% overall).
• Patients who received cell-based therapies (CAR T-cell therapy or another T-cell engager) tended to do somewhat better.
Side effects and safety
• About 10% of patients stopped teclistamab due to serious infections, and 4.5% died from infection-related complications.
• Side effects like cytokine release syndrome and nerve effects were mostly mild (grade 1–2).
Other observations
• Around one in four patients who relapsed had disease that was difficult to detect with blood tests (“nonsecretory” or “oligo-secretory” myeloma). → Imaging (such as PET/CT or MRI) is important for follow-up.
• Patients previously treated with other BCMA-targeted drugs (like CAR T or belantamab) could still respond to Teclistamab.
Conclusions
• Teclistamab provides meaningful benefits for heavily pretreated myeloma patients, but relapse remains common and survival after relapse is poor.
• New strategies and access to advanced immunotherapies (like CAR T and next-generation bispecific antibodies) are urgently needed to improve outcomes after teclistamab failure.
Reference:
Yu, K.L., Ho, M., Paruzzo, L. et al. Outcomes of relapse after teclistamab therapy in multiple myeloma. Blood Cancer J. 15, 193 (2025). https://doi.org/10.1038/s41408-025-01408-4
Talquetamab in relapsed refractory multiple myeloma: multi-institutional real-world study — Blood Cancer Journal (November 2025)
Background
Talquetamab is a bispecific antibody approved for patients with relapsed/refractory multiple myeloma. This real-world study looked at 114 patients who had already received an average of six previous therapies.
Key findings
• Response: About 73% of patients responded to talquetamab treatment.
◦ 26% had a complete response (no detectable myeloma).
◦ 26% had a very good partial response.
• Survival:
◦ After 6 months, 86% of patients were alive.
◦ 56% had no disease progression at 6 months.
◦ The median time before the disease worsened was 10 months.
Side effects
• Cytokine release syndrome (CRS): 54% of patients; severe cases (grade ≥2) in 7%.
• Infections: 27% overall (about 14% within 3 months); most were viral. Over half of infections required hospitalization, but no infection-related deaths occurred.
• Neurological side effects (ICANS): 10% of patients.
• Weight loss: Common and significant — average 9% body weight loss at 6 months.
Why this study matters
• Talquetamab is effective even in patients whose disease no longer responds to multiple prior treatments, including those who already received other modern antibody therapies.
• While the treatment works well, it can cause notable side effects — especially infections and progressive weight loss — which require close monitoring, nutritional support, and preventive care.
• Real-world results match those seen in clinical trials, confirming talquetamab as an important option for patients with difficult-to-treat multiple myeloma.
Reference:
Al Hadidi, S., Szabo, A., Mohan Lal, B. et al. Talquetamab in relapsed refractory multiple myeloma: multi-institutional real-world study. Blood Cancer J. 15, 196 (2025). https://doi.org/10.1038/s41408-025-01386-7
The impact of STAiR18 on multiple myeloma survival rates — Journal of Translational Medicine (November 2025)
Background
Multiple myeloma often grows rapidly and is difficult to cure. Researchers have discovered that a molecule called STAiR18, a type of long non-coding RNA (lncRNA), is found at high levels in patients with more aggressive myeloma and poorer outcomes. However, how STAiR18 contributes to MM growth was not well understood.
What is the purpose of the study?
This study explored how STAiR18 works in myeloma cells and mice. The researchers found that another molecule, STAT3, increases the production of STAiR18. Once made, STAiR18 mainly stays in the cell’s cytoplasm, where it interacts with a small RNA called miR-451a. Normally, miR-451a helps block cancer growth by silencing a receptor called IL-6R, which is part of the IL-6R/STAT3/JAK2 signaling pathway—a key system that promotes cell growth and survival.
However, STAiR18 “sponges up” miR-451a, preventing it from doing its job. This allows IL-6R levels to rise, which then activates the STAT3 and JAK2 proteins, further increasing STAiR18 levels—a positive feedback loop that drives MM cell growth.
When researchers reduced STAiR18 levels in MM cells or in mice, tumor growth slowed down, and cancer cell proliferation decreased.
Key takeaways
• STAiR18 is highly expressed in multiple myeloma and linked to worse patient outcomes.
• STAT3 activates STAiR18, and STAiR18 in turn boosts the IL-6R/STAT3/JAK2 pathway.
• STAiR18 blocks miR-451a, removing its tumor-suppressing effect.
• Together, these interactions form a self-reinforcing loop that promotes MM cell growth.
• Targeting STAiR18 could be a promising new approach to treating multiple myeloma.
Reference:
Wu, Y., Wang, H., Luo, J. et al. The impact of STAiR18 on multiple myeloma survival rates. J Transl Med 23, 1243 (2025). https://doi.org/10.1186/s12967-025-07210-x
Clinical Trials
Fully Human anti-GPRC5D CAR T-Cell Therapy RD118 Induces Durable Remissions in Relapsed/Refractory Multiple Myeloma — Blood (October 2025, Brief Report)
Background
The RD118 study tested a new type of CAR T-cell therapy that targets GPRC5D, a promising marker for treating relapsed or refractory multiple myeloma (RRMM). The study included 18 patients who had already received many prior therapies, including one with primary plasma cell leukemia (pPCL).
How was the study conducted? What are the key findings?
Patients received a single infusion of RD118, and after a median follow-up of 17 months, the results were highly encouraging: 94.4% responded to treatment, with 72.2% achieving a complete or near-complete response. Even among patients who had relapsed after previous BCMA-targeted CAR T therapy, the response rate was 85.7%. The median time before the disease worsened (progression-free survival) was 18.2 months, and after one year, 82% of patients were still progression-free, and 93% were alive.
Side effects
Most side effects were manageable. About 89% of patients experienced mild to moderate cytokine release syndrome (CRS), a common immune reaction to CAR T therapy. Only one patient developed a short-term, severe neurological side effect that resolved within three days. No serious brain-related side effects or treatment-related deaths occurred.
Conclusion
Overall, RD118 showed strong and lasting effectiveness with an acceptable safety profile, offering hope for patients with hard-to-treat multiple myeloma.
Reference:
Mengmeng Pan, Di Wang, Jie Xu, Shiwei Jin, Yan Wang, Yi Tao, Yuanfang Liu, Wanyan Ouyang, Xiangqin Weng, Hongmei Yi, Yu Huang, Xinmei Cao, Shuhua Li, Fuyuan Zhang, Weiping Zhang, Chunrui Li, Jian-Qing Mi; Fully Human anti-GPRC5D CAR T-Cell Therapy RD118 Induces Durable Remissions in Relapsed/Refractory Multiple Myeloma. Blood 2025; blood.2025030559. doi: https://doi.org/10.1182/blood.2025030559
The impact of daratumumab-containing induction on stem cell mobilization, collection and engraftment in newly diagnosed multiple myeloma: results of the prospective DILEMMA study — Haematologica (October 2025)
Background
For younger, healthy patients with newly diagnosed multiple myeloma, autologous stem cell transplantation (ASCT) remains a key part of treatment. To perform this procedure, enough stem cells (CD34+ cells) must be collected from the patient’s blood after special medications stimulate their release.
Recently, adding daratumumab (a targeted antibody therapy) to early treatment has improved cancer control. However, doctors have noticed it might make stem cell collection more difficult, requiring more medications and time to gather enough cells.
What is the DILEMMA Study?
This study, conducted at Fondazione Policlinico A. Gemelli IRCCS (Italy) between 2023 and 2024, compared two groups of patients with newly diagnosed multiple myeloma (NDMM):
• 66 patients who received daratumumab-containing treatment, and
• 84 patients treated earlier (before daratumumab was used).
All were candidates for ASCT and underwent standard stem cell collection using cyclophosphamide (chemotherapy) plus G-CSF, with plerixafor added if needed to boost stem cell release.
Key findings
• Stem cell collection success: Almost all patients, including those treated with daratumumab, successfully collected enough stem cells for at least one transplant.
• Lower stem cell counts: Patients who had received daratumumab had lower numbers of circulating stem cells before and during collection.
• More plerixafor needed: About 27% of daratumumab-treated patients needed plerixafor, compared with 9% of those who did not receive daratumumab.
• No transplant failures: All patients eventually achieved blood cell recovery after transplant.
• Slightly higher platelet transfusion needs: Daratumumab-treated patients needed more platelet transfusions after the first transplant, but overall recovery was similar.
What this means
• Daratumumab can make stem cell collection more challenging, likely by reducing the number of circulating stem cells.
• Using the right dose of cyclophosphamide and plerixafor when needed can overcome this issue, ensuring enough cells for transplantation.
• Transplant success and recovery remain excellent, even after daratumumab treatment.
• Future work should refine personalized mobilization strategies to maintain effectiveness while controlling costs.
Reference:
Valentini CG, Pellegrino C, Chiusolo P, Rossi E, Ladiana R, Za T, Sica S, Pagano L, De Stefano V, Teofili L. The impact of daratumumab-containing induction on stem cell mobilization, collection and engraftment in newly diagnosed multiple myeloma: results of the prospective DILEMMA study. Haematologica; https://doi.org/10.3324/haematol.2025.288411 [Early view].
Long term Follow-up of Zevor-cel in Patients with Relapsed/Refractory Multiple Myeloma — Blood Advances (October 2025)
Background
Patients with relapsed or refractory multiple myeloma (RRMM) often stop responding to standard treatments. Zevorcabtagene autoleucel (zevor-cel) is a new CAR T-cell therapy that targets B-cell maturation antigen (BCMA), a protein found on myeloma cells.
Study overview
• Phase 1, multi-center trial (LUMMICAR Study 1, China)
• 14 patients with RRMM who had already received at least 3 prior treatments
• Treatment: A single infusion of zevor-cel
• Follow-up: Median of 53.3 months (about 4.5 years)
Key results
• Response rate: 100% of patients responded to treatment
• Deep responses: 78.6 % achieved complete response or better, and 92.9% had a very good partial response or better
• Response duration: Median response lasted about 25 months, and 42% of patients maintained response for 3 years or longer
• Survival: After 5 years, 77% of patients were still alive
Safety and side effects
• Most patients (93%) had only mild to moderate cytokine release syndrome (CRS) — a common and expected side effect of CAR T therapy
• No severe (grade 3 or higher) CRS, no neurological side effects, and no new or delayed safety issues were reported
• No treatment-related deaths occurred
Conclusion
After nearly 5 years of follow-up, zevor-cel continues to show lasting responses and excellent safety in patients with hard-to-treat multiple myeloma. These results suggest that zevor-cel is a promising and well-tolerated long-term treatment option for RRMM.
Reference:
Chengcheng Fu, Wenming Chen, Zhen Cai, Lingzhi Yan, Huijuan Wang, Jingjing Shang, Yin Wu, Shuang Yan, Wen Gao, Xiaolan Shi, Xiaoyan Han, Fang Tang, Gaofeng Zheng, Yanling Wen, Xingxing Meng, Daijing Yuan, Huamao Wang, Zonghai Li; Long term Follow-up of Zevor-cel in Patients with Relapsed/Refractory Multiple Myeloma. Blood Adv 2025; bloodadvances.2025017365. doi: https://doi.org/10.1182/bloodadvances.2025017365
Patient-reported outcomes with belantamab mafodotin, pomalidomide, and dexamethasone versus bortezomib, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-8): a phase 3, open-label, randomised controlled trial — The Lancet Haematology (November 2025)
Summary
The DREAMM-8 study tested two treatment combinations for people with relapsed or refractory multiple myeloma.
The two treatment groups were:
1. Belantamab mafodotin + pomalidomide + dexamethasone
2. Bortezomib + pomalidomide + dexamethasone
Over 300 patients from 18 countries took part. The goal was to see how treatment affected quality of life and symptom control, as reported by the patients themselves.
Results
• Both groups had stable quality of life during treatment.
• More patients in the belantamab group reported meaningful improvement in how they felt and functioned.
• Most side effects were mild or manageable.
• Blurred vision was the most common severe symptom with belantamab (43% of patients), followed by fatigue.
• Other side effects were similar between groups.
Conclusion
Belantamab mafodotin, when combined with pomalidomide and dexamethasone, helped maintain patients’ quality of life and was generally well tolerated. Eye-related side effects were manageable. This supports its use as a treatment option for people whose myeloma has returned or stopped responding to previous therapy.
Reference:
Meletios A Dimopoulos, Meral Beksac, et al, Patient-reported outcomes with belantamab mafodotin, pomalidomide, and dexamethasone versus bortezomib, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-8): a phase 3, open-label, randomised controlled trial, The Lancet Haematology, Volume 12, Issue 11,2025, Pages e876-e886,ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(25)00256-X.
U.S. Food and Drug Administration (FDA)
FDA approves Darzalex Faspro® (daratumumab and hyaluronidase-fihj) for high-risk smoldering multiple myeloma
On Thursday, November 6, the U.S. Food and Drug Administration approved Darzalex Faspro® (daratumumab and hyaluronidase-fihj) for adults with high-risk smoldering multiple myeloma (HRSMM).
According to a press release from Johnson & Johnson, “Darzalex Faspro is the first and only approved treatment for HR-SMM, enabling earlier intervention before the disease progresses to active multiple myeloma.”
The FDA approval was based on findings from the open-label randomized AQUILA trial (NCT03301220), which evaluated the effectiveness of Darzalex Faspro (daratumumab and hyaluronidase-fihj) compared with active monitoring in 390 patients with high-risk smoldering multiple myeloma (SMM). Darzalex Faspro is approved only for patients with high-risk SMM, not for lower-risk categories.
Patients in the treatment group received Darzalex Faspro as a subcutaneous injection weekly for 8 weeks — every 2 weeks from weeks 9 to 24, and then once every 4 weeks starting at week 25, until 39 cycles, or up to 36 months, or until disease progression or unacceptable toxicity.
41% of patients had two or more high-risk features, such as high blood levels of monoclonal protein (>2 g/dL), an abnormal serum-free light chain ratio (>20), or more than 20% plasma cells in the bone marrow.
“The major efficacy outcome measure was progression-free survival (PFS) by independent review committee (IRC) as defined as the diagnosis of multiple myeloma based on the International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma or death. Median PFS was not evaluable in the daratumumab and hyaluronidase-fihj arm and 41.5 months in the active monitoring arm (Hazard ratio 0.49 [95% CI: 0.36-0.67]; p-value <0.0001),” states the FDA.
“Darzalex Faspro is a foundational therapy in multiple myeloma and illustrates our commitment to improve outcomes for patients at every stage of their disease. Data from the AQUILA study reinforce the significant impact Darzalex Faspro continues to have for patients. With today’s approval, patients with HR-SMM will now be able to receive this treatment before they progress to active multiple myeloma, giving us the opportunity to shift the treatment paradigm and bring hope to people who are impacted by this disease,” said Jordan Schecter, MD, Vice President, Research & Development, Multiple Myeloma, Oncology, Johnson & Johnson Innovative Medicine.
According to the FDA, “the prescribing information for daratumumab and hyaluronidase-fihj includes warnings and precautions for hypersensitivity and other administration reactions, cardiac toxicity in patients with light chain amyloidosis, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interference with cross-matching and red blood cell antibody screening.” Full prescribing information for Darzalex Faspro will be posted on Drugs@FDA.
To learn more, read the FDA announcement and the Johnson & Johnson press release.
References:
• FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma, November 6, 2025. Resources for information, approved drugs.
• DARZALEX FASPRO® is the first and only treatment approved by the U.S. FDA for patients with high-risk smoldering multiple myeloma, Johnson & Johnson press release, November 6, 2025.
FDA grants 510(k) clearance to Thermo Fisher’s EXENT System to aid in diagnosis of multiple myeloma
On Wednesday, November 12, Thermo Fisher Scientific Inc. announced via a press release that the U.S. Food and Drug Administration has given a 510(k) clearance to EXENT® Analyser and Immunoglobulin Isotypes (GAM) Assay — “a first-of-its-kind automated platform for clinical laboratories.”
According to Thermo Fisher, the EXENT System uses enhanced sensitivity to accurately detect M-proteins by their unique molecular weight. This allows it to clearly distinguish natural proteins from those produced by therapeutic antibodies. These precise results help doctors better understand a patient’s disease status and support diagnosis and monitoring of conditions such as multiple myeloma, smoldering multiple myeloma, Waldenström’s macroglobulinemia, amyloid light-chain (AL) amyloidosis, and monoclonal gammopathy of undetermined significance (MGUS).
Dr. Noemi Puig of the department of hematology in University Hospital Salamanca in Spain, and a leader in multiple myeloma clinical research stated: “The clearance of the EXENT System represents a significant advancement in the tools available to aid in the diagnosis of multiple myeloma. By combining increased sensitivity with ease of use and automated workflows, laboratories can achieve greater clarity and diagnostic confidence, ultimately supporting improved patient care.”
“Our continued goal is to equip laboratories and clinicians with technologies that deliver greater accuracy, efficiency and clarity, enabling more informed clinical decisions and improving the patient journey. The EXENT System reflects Thermo Fisher’s commitment to advancing diagnostic solutions that meet well-defined clinical needs,” said Stephen Harding, vice president and general manager, protein diagnostics at Thermo Fisher Scientific.
Reference:
Thermo Fisher Scientific Receives 510(k) Clearance in the United States for EXENT System* to Aid in the Diagnosis of Multiple Myeloma, Thermo Fisher press release, November 12, 2025.
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