A summary of some notable key multiple myeloma research from January-February 2026

Scope and Methodology  
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from January-February 2026. Content was developed by the International Myeloma Foundation medical editorial team using various medical abstracts on new guidelines, recommendations, reviews, letters to the editor, correspondence, and the latest results of ongoing clinical trials. It is intended for patients, care partners, and oncology professionals. This blog article was medically reviewed by Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, on February 25, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.  

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

Guidelines/Recommendations
 

Actionable Steps to Address Disparities in Healthcare Among US Patients With Multiple Myeloma: A Patient Perspective — Journal of Cancer Education (January 2026)

Background  
Two U.S. Multiple Myeloma (MM) Health Equity Summits brought together patients with MM, patient advocates, healthcare providers (HCPs), and industry representatives to discuss inequities in MM care. Participants identified key problems affecting the patient experience and agreed on actions to improve awareness, understanding, and access to care—especially for Black patients, who are disproportionately affected by MM and face worse outcomes.

Key findings

1. Lack of awareness leads to delayed diagnosis. 
Many non-specialist HCPs and patients are unfamiliar with MM symptoms, which are often vague (such as bone pain or fatigue). This lack of awareness is a major cause of delayed diagnosis. Improved MM education and training for HCPs, along with better patient education through multiple communication channels, support groups, and community health workers, could help patients be diagnosed earlier and advocate for themselves.

2. Barriers to accessing optimal care. 
Geographic distance, financial challenges, cultural factors, and insurance issues often limit access to MM specialists and advanced treatments. Suggested solutions include expanding telehealth, reducing bias in referral patterns, using patient navigators to help with insurance and logistics, and improving understanding and trust around clinical trials.

Core themes from the discussions

• Trust between patients and HCPs. 
Historical mistreatment, systemic racism, and ongoing discrimination have reduced trust in the healthcare system among Black patients. Respectful, culturally appropriate, and open communication can help rebuild trust. Addressing issues such as pain management during procedures (e.g., bone marrow biopsies) and encouraging shared decision-making are essential.

• Bidirectional understanding and patient empowerment. 
Effective care requires both patients' understanding of medical information and HCPs understanding of patients’ cultural, social, and personal contexts. Barriers such as language, health literacy, and socioeconomic challenges can limit engagement. Supportive care teams (e.g., social workers and palliative care specialists) can help address symptoms, emotional distress, and social determinants of health (SDOH).

• Racially concordant care. 
When patients and HCPs share similar racial backgrounds, trust, communication, and care experiences often improve. However, Black HCPs are underrepresented. Policies that support recruiting and retaining a more diverse healthcare workforce are needed.

Recommended actions

1. For healthcare providers

    • Build strong, trusting relationships through open communication. 
    • Practice cultural humility and consider patients’ SDOH and preferences. 
    • Explain MM and treatment options clearly, including clinical trials. 
    • Connect patients with resources to address social and financial barriers.

2. For the MM community and policymakers

    • Increase diversity in the healthcare workforce. 
    • Improve education on MM symptoms for HCPs, payers, and communities to reduce time to diagnosis. 
    • Expand access to clinical trials, including participation at community treatment centers.

3. For patients

    • Engage with advocacy and community organizations for education and support. 
    • Use patient navigators to understand insurance and care options. 
    • Seek second opinions when needed.

Conclusion 
The MM Health Equity Summits highlighted how race, social determinants of health, and medical mistrust affect access to equitable MM care. By improving awareness, building trust, empowering patients, increasing workforce diversity, and expanding access to specialized care and clinical trials, meaningful progress can be made toward reducing long-standing inequities and improving outcomes for all patients with MM.

Reference: 
Gilbert, O., Aiello, J., Omel, J. et al. Actionable Steps to Address Disparities in Healthcare Among US Patients With Multiple Myeloma: A Patient Perspective. J Canc Educ (2026). https://doi.org/10.1007/s13187-025-02798-6  

ESR Essentials: bone marrow MRI in oncology—practice recommendations by the European Society of Musculoskeletal Radiology — European Radiology (February 2026)

Background 
Cancer can spread to the bone marrow in many solid tumors and in multiple myeloma (MM). Detecting these bone marrow lesions early, determining how advanced the disease is (staging), checking how well treatment is working, and identifying recurrence or complications are all essential for good patient care.

MRI of the bone marrow is now recommended as the main imaging test for patients with suspected bone metastases from solid cancers or for staging and follow-up of multiple myeloma. MRI is more sensitive and accurate than X-rays, bone scintigraphy, or CT, and it does not use ionizing radiation. For these reasons, MRI should replace these older imaging methods whenever possible.

MRI can be used for:

    • Diagnosing bone marrow involvement 
    • Staging disease 
    • Assessing response to treatment 
    • Detecting residual or recurrent disease 
    • Evaluating bone-related complications

Whole-body MRI (WB-MRI) is preferred when a complete assessment of the skeleton is needed, such as at initial staging. Axial skeleton MRI (AS-MRI) is a faster and reliable alternative for focused evaluations or routine follow-up.

MRI protocols should be adapted to the specific cancer type and clinical situation, following established disease-specific guidelines. Standard protocols should include:

    • Fast spin echo T2 Dixon sequences (to assess bone marrow fat and water content) 
    • Diffusion-weighted imaging (DWI) (to detect cancer infiltration)

Quantitative MRI measurements, such as the apparent diffusion coefficient (ADC) and fat fraction (FF), improve diagnostic accuracy and help monitor treatment response over time.

Radiologists must understand typical patterns of cancer spread in the bone marrow, treatment-related changes, and common imaging pitfalls to avoid misinterpretation.

Why these recommendations matter 
Overall, bone marrow MRI plays a central role in modern cancer imaging. It provides a radiation-free, highly sensitive, whole-skeleton assessment and is now recommended alongside PET/CT for staging and treatment response evaluation. These recommendations aim to support consistent, high-quality use of bone marrow MRI in routine oncologic care.

Reference: 
Lecouvet, F.E., Taihi, L., Kirchgesner, T. et al. ESR Essentials: bone marrow MRI in oncology—practice recommendations by the European Society of Musculoskeletal Radiology. Eur Radiol (2026). https://doi.org/10.1007/s00330-025-12307-4

Review

Diagnosis, risk stratification and management of smoldering multiple myeloma — Nature Reviews Clinical Oncology (January 2026)

Summary 
Smoldering multiple myeloma (SMM) is an early, symptom-free stage that always comes before multiple myeloma (MM). While new treatments have greatly improved survival in MM, the disease often causes permanent damage by the time it becomes “active,” as defined by the 2014 International Myeloma Working Group SLiM–CRAB criteria. Preventing or delaying this progression is an important goal.

The course of SMM varies widely. Some people have low-risk SMM that progresses very slowly and behaves similarly to monoclonal gammopathy of undetermined significance (MGUS). In contrast, high-risk SMM progresses much faster: about 40–50% of patients develop symptomatic MM within 2 years, and overall, SMM carries about a tenfold higher risk of progression to MM in the first 5 years compared with MGUS.

Modern imaging, especially PET–CT and MRI, is essential to confirm the diagnosis of SMM, exclude active MM, and better estimate the risk of progression. Although several risk-stratification tools are available and widely used, they do not fully capture the underlying biology of the disease, and better models are needed.

For patients with high-risk SMM, two main management strategies are reasonable: careful observation (active monitoring) or early treatment using therapies developed for MM. The choice between these options should be individualized through a detailed discussion of potential benefits and risks. Ongoing and future clinical trials aim to refine risk prediction, select meaningful end points, and determine whether early treatment can safely improve long-term outcomes for patients with SMM.

Reference: 
Zanwar, S., Kumar, S. & Rajkumar, S.V. Diagnosis, risk stratification and management of smouldering multiple myeloma. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01119-0  

Advances in the pathophysiology and treatment of anemia in multiple myeloma — Current Opinion in Hematology (February 2026)

Background 
Anemia (low hemoglobin levels) is very common in people with multiple myeloma (MM). It can cause fatigue, weakness, shortness of breath, and reduced quality of life. Anemia in MM has multiple causes, including both the disease itself and the treatments used to control it.

With the introduction of newer immunotherapies, treatment-related anemia has become increasingly important.

Why does anemia occur in myeloma? 
Anemia can result from:

    • Bone marrow infiltration by myeloma cells 
    • Inflammation and cytokine release 
    • Impaired iron metabolism 
    • Kidney dysfunction 
    • Drug-related bone marrow suppression

Many modern MM treatments can directly or indirectly suppress red blood cell production.

Immunotherapy-induced anemia

1. Immunomodulatory drugs (IMiDs) and CELMoDs 
Lenalidomide and pomalidomide are key MM treatments that improve progression-free survival (PFS) and overall survival (OS). Newer drugs such as iberdomide (CC-220) belong to a group called CELMoDs.

However, these drugs frequently cause anemia, as they can:

    • Directly suppress red blood cell precursors in the bone marrow 
    • Increase inflammatory cytokines such as interferon-γ (IFN-γ) 
    • Disrupt iron balance 
    • Degrade important transcription factors (IKZF1 and IKZF3) involved in normal blood formation

How common is severe anemia?

    • Lenalidomide: Grade 3–4 anemia in up to 15–20% of patients 
    • Pomalidomide (MM-003 trial): Grade ≥3 anemia in 22–28% ; Real-world studies report up to 30–40% in heavily pretreated patients 
    • Iberdomide (CC-220-MM-001 trial): Grade ≥3 anemia in about 28% ; Lower rates (0–5%) seen in maintenance settings (EMN26 trial)

The risk increases in:

    •    Heavily pretreated patients 
    •    Patients with poor kidney function 
    •    Those receiving combination therapies

Management includes dose adjustments, alternate-day dosing, growth factor support, and careful monitoring.

2. Anti-CD38 monoclonal antibodies

Drugs such as daratumumab and isatuximab have significantly improved MM outcomes but can also cause anemia.

CD38 is found not only on myeloma cells but also on early red blood cell precursors. Anti-CD38 antibodies may:

    • Directly suppress red blood cell production 
    • Alter cytokine levels (e.g., IL-6) 
    • Reduce responsiveness to erythropoietin 
    • Cause inflammation in the bone marrow

Clinical trial data

    • Daratumumab + pomalidomide + dexamethasone (DPd): Grade 3–4 anemia in ~18% 
    • ICARIA-MM trial (Isatuximab + pomalidomide + dexamethasone, IsaPd): Grade ≥3 anemia in 25–30% 
    • IKEMA trial (Isatuximab + carfilzomib + dexamethasone, IsaKd): Grade ≥3 anemia in 16–24%

Iron deficiency is also common in patients receiving daratumumab, possibly due to inflammation. Monitoring hemoglobin, ferritin, and transferrin saturation is recommended.

Importantly, daratumumab can interfere with blood compatibility testing (Coombs test), which may delay transfusions but does not usually cause true hemolysis.

3. Bispecific antibodies (BsAbs) 
New T-cell–redirecting therapies such as teclistamab, talquetamab, and elranatamab have transformed treatment for relapsed/refractory MM.

Anemia is common:

    •    Occurs in 45–67% of patients 
    •    Grade ≥3 anemia in up to 50% 
    •    A pooled analysis (2,374 patients) showed: 
          - 39.2% any-grade anemia 
          - 24.5% grade ≥3 anemia

Rates were higher with BCMA-directed bispecific antibodies compared to GPRC5D/FcRH5-targeting agents.

4. CAR T-cell therapy 
CAR T-cell therapies targeting BCMA include:

    • Idecabtagene vicleucel (ide-cel) – approved based on the KARMMA-3 trial

          - 66% any-grade anemia 
          - 51% grade 3–4 anemia

    • Ciltacabtagene vicleucel (cilta-cel) – approved based on the CARTITUDE-4 trial

           - 54.3% any-grade anemia 
           - 35.6% grade 3–4 anemia

After CAR T-cell therapy, prolonged low blood counts are now termed immune effector cell–associated haematological toxicity (ICAHT).

CAR T cells release inflammatory cytokines such as IFN-γ, IL-6, IL-10, and TNF-α. These suppress red blood cell production.

Risk factors include:

    • High disease burden 
    • Many prior treatments 
    • Elevated inflammation markers 
    • Poor baseline bone marrow reserve

The CAR-HEMATOTOX score helps predict which patients are at higher risk of prolonged cytopenias.

Treatment of anemia in myeloma 
The first step in managing anemia is to treat the myeloma itself, as controlling the disease often leads to improvement in hemoglobin levels. When anemia is severe or causing symptoms, red blood cell transfusions are recommended, particularly when hemoglobin falls below 7 g/dL.

Another treatment option is the use of erythropoiesis-stimulating agents (ESAs), such as epoetin or darbepoetin alfa. These medications help increase hemoglobin levels and reduce the need for transfusions. However, they may increase the risk of blood clots (thrombosis), especially when used together with immunomodulatory drugs (IMiDs).  

Guidelines from ASCO and ASH recommend considering ESAs for patients with chemotherapy-associated anemia when treatment is not intended to be curative, with the goal of reducing transfusion requirements.

New treatments under investigation 
Activin receptor fusion proteins are a newer treatment strategy designed to stimulate red blood cell production by targeting the TGF-β/SMAD signaling pathway.  

One such drug is sotatercept (ACE-011), an activin receptor type IIa ligand trap. Sotatercept promotes erythroid differentiation by reducing SMAD2/3 signalling and acts on late-stage erythroid progenitor cells to enhance red blood cell production.

In a clinical trial combining sotatercept with melphalan, prednisone, and thalidomide (MPT), medium and high doses of sotatercept improved haemoglobin levels, demonstrating a dose–response effect. An ongoing study (NCT01562405) is evaluating sotatercept in combination with lenalidomide or pomalidomide plus dexamethasone in patients with multiple myeloma.

Another investigational agent is INCB000928, an ALK-2 inhibitor currently being studied in a phase 1/2 clinical trial (NCT04582539). This trial includes patients with multiple myeloma who are transfusion-dependent or have symptomatic anemia.

Key takeaways

    • Anemia in multiple myeloma is caused by both the disease and its treatments. 
    • Modern immunotherapies (IMiDs, anti-CD38 antibodies, bispecific antibodies, CAR T cells) significantly increase the risk of anemia. 
    • Severe anemia (grade ≥3) occurs in: 
           - 15–30% with IMiDs 
           - 16–30% with anti-CD38 combinations 
           - Up to 50% with bispecific antibodies 
           - 35–51% with CAR T-cell therapies

    • Monitoring hemoglobin and iron levels is essential. 
    • Treatment includes transfusions, cautious use of ESAs, and emerging drugs such as sotatercept. 
    • Early recognition and management are critical to maintaining quality of life and avoiding complications.

As immunotherapy use expands, careful monitoring and individualized management of anaemia are increasingly important in multiple myeloma care.

Reference: 
Giuliani, Nicolaa,b; dalla Palma, Benedettab; Notarfranchi, Laurac. Advances in the pathophysiology and treatment of anaemia in multiple myeloma. Current Opinion in Hematology ():10.1097/MOH.0000000000000911, February 11, 2026. | DOI: 10.1097/MOH.0000000000000911

Research

Temporal trends in progression risk in smoldering myeloma: a systematic review — EClinical Medicine (January 2026)

What is the purpose of the study? 
Smoldering multiple myeloma (SMM) is an early, symptom-free stage of myeloma that does not always progress to active disease. Over the past decade, diagnosis and classification of SMM have improved. These changes may have altered how often and how quickly SMM progresses to active multiple myeloma (MM). Until now, this has not been carefully measured.

How was the study conducted? 
Researchers reviewed 14 published studies (from 1970–2024) including patients with SMM. They reconstructed individual patient data by digitizing published Kaplan–Meier time-to-progression (TTP) curves and analyzed outcomes using modern statistical methods. The review was registered in PROSPERO (ID 1068697).

Key findings

    • Across all patients with SMM, the risk of progression was 22.8% at 2 years and 60.1% at 10 years 
    • In high-risk SMM, progression risk was higher: 44.7% at 2 years and 85.6% at 10 years 
    • After remaining stable for 5 years, progression risk decreased substantially: 
          - All-risk patients: 14.2% at 2 years and 30.8% at 5 years after the 5-year mark 
          - High-risk patients: 22.5% at 2 years and 50.6% at 5 years after the 5-year mark 
    • Patients enrolled before 2014 progressed faster than those diagnosed more recently. 
    • Median TTP steadily improved over time: 
          - 60.9 months in early reports 
          - 62.1 months in the cohort underlying the Mayo 20/20/20 model 
          - 76.4 months in the IMWG risk model cohort 
          - In recent studies (e.g., lenalidomide vs observation trial, Greek observational study), the median TTP was not reached, indicating very slow progression

    • Even among high-risk patients, median TTP improved: 
          - 19.7 months (de Daniel et al.) 
          - 26.4 months (QUIREDEX trial) 
          - 41.8 months (AQUILA trial) 
          - 51.5 months (Greek study)

Why SMM looks more “benign” today 
Several important changes explain these findings:

1. Updated IMWG diagnostic criteria (2014) now classify patients with: 
    •  ≥60% bone marrow plasma cells 
    •  Free light chain ratio >100 
    •  1 focal MRI lesion as having active myeloma, not SMM.

2. Modern imaging (MRI, PET/CT, low-dose CT) detects bone disease missed by older X-rays. 
3. Earlier and broader testing identifies SMM at lower M-protein levels. 
4. Specialist care by hematologists has improved diagnostic accuracy. 
5. An aging population increases detection of early plasma cell disorders.

As a result, many patients previously labeled as SMM would now be diagnosed with active myeloma and treated earlier.

Risk models may need updating 
Widely used models such as the Mayo 20/20/20 and IMWG risk stratification system were developed using older patient cohorts and may overestimate progression risk for patients diagnosed today. Some patients labeled “high-risk” may actually have a much slower disease course.

New insights into disease behavior 
The study suggests at least two biological subgroups of SMM: 
    • One with earlier, more aggressive progression 
    • Another with slow early behavior but possible later progression (often after 7–8 years)

This finding has implications for long-term monitoring, even in patients initially considered low or intermediate risk.

Future directions 
More accurate prediction of progression will likely come from: 
    • Genomic profiling (e.g., MAPK pathway mutations such as KRAS, NRAS, BRAF) 
    • Dynamic risk models that track changes over time (e.g., hemoglobin, M-protein, free light chains) 
    • Integrated models such as PANGEA, which combine baseline and follow-up data 
    • Emerging blood-based genomic testing of circulating plasma cells

Several novel immunotherapies have already shown very high response rates and minimal residual disease (MRD) negativity in selected high-risk patients.

What this means for patients 
Modern SMM is generally less aggressive than it was 15–20 years ago. Many patients can safely avoid early treatment and its side effects, while careful monitoring identifies those who truly need therapy. Updating risk models to reflect modern diagnostics will help ensure that treatment is given only when it is likely to provide real benefit.

Reference: 
Ludwig H, Kastritis E, Bernhard S, van de Donk NWCJ, Boccadoro M, Terpos E, Musto P, Sonneveld P, Mohyuddin GR. Temporal trends in progression risk in smoldering myeloma: a systematic review. EClinicalMedicine. 2026 Jan 8;91:103750. doi: 10.1016/j.eclinm.2025.103750.

Screening for monoclonal gammopathies in the adult population of Uruguay — Blood Global Hematology (January 2026)

What is the purpose of the study? 
Multiple myeloma (MM) is often diagnosed late because early symptoms are vague. Earlier stages of MM such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) can be found with simple blood tests. This study looked at how common these conditions are in Uruguay.

How was the study conducted? 
Between October 2021 and October 2022, 3,905 adults over 40 years of age from public and private healthcare centers in Uruguay were screened using blood protein tests.

Key findings 
    •    MGUS: found in 2.45% of participants 
    •    SMM: found in 0.02% 
    •    Multiple myeloma: found in 0.07%

This is the first study to report these rates in the Uruguayan population. People diagnosed with active disease received early treatment according to international guidelines, and none had organ damage at diagnosis, showing the benefit of early detection.

Who is most at risk? 
MGUS was much more common in people older than 55 years, confirming that risk increases with age.

Why this study matters 
These findings suggest that age-targeted screening (starting around age 55) could help detect plasma cell disorders earlier, allow timely treatment, reduce complications, and support better healthcare planning in Uruguay.

Key takeaway for patients 
Simple blood screening in older adults can identify early stages of myeloma before symptoms or organ damage occur, offering clear benefits for patients and the health system.

Reference: 
Eloísa Riva, Lucía Pérez, David Israel Garrido, Alicia Olascoaga, Felipe Lemos, Antonella Acerbis, Ana Vallega, Jacqueline Zipitría, Andrea Trucido, Gabriela Villanueva, Nahir Correa, Raquel Ballesté, Nicolás Marchetti, Andrea Urbin, Nadia Krul; Screening for monoclonal gammopathies in the adult population of Uruguay. Blood Global Hematology 2026; 100061. doi: https://doi.org/10.1016/j.bglo.2026.100061

Treatment Initiation Among Black and White Older Adults With Multiple Myeloma: A SEER-Medicare Analysis — Cancer Medicine (January 2026)

What is the purpose of the study? 
This study examined whether older Black adults with multiple myeloma (MM) start treatment later than White adults, and whether this difference has changed over time. The researchers studied patients diagnosed between 2007 and 2017, a period when many effective MM treatments were already available.

How was the study conducted? 
The study included Black and White adults aged 65 and older with MM identified from the SEER-Medicare database. All patients had continuous Medicare coverage, including Part D, so their cancer treatments could be tracked accurately.

Researchers measured the time from diagnosis to starting treatment, comparing Black and White patients across three time periods (2007–2010, 2011–2014, and 2015–2017). They used statistical models to estimate how quickly patients began treatment and the percentage who started treatment within 3, 6, and 12 months after diagnosis.

Key findings

    • White patients were consistently more likely to start MM treatment than Black patients in all time periods. 
    • White patients started treatment about 35–36% faster than Black patients (hazard ratios ranged from 1.35 to 1.36). 
    • The difference in treatment initiation between Black and White patients remained significant and consistent at 3, 6, and 12 months after diagnosis, with absolute differences ranging from 9% to 11%. 
    • Contrary to expectations, these racial disparities did not increase over time, but they also did not improve.

Overall treatment rates 
Although treatment initiation increased over time for both groups, many patients still did not start treatment within one year. In the most recent period (2015–2017):

    • 58% of Black patients started treatment within 12 months 
    • 69% of White patients started treatment within 12 months

Some patients may not have required treatment because they had smoldering multiple myeloma (SMM), a related condition that does not need immediate therapy. However, evidence suggests that Black and White patients are equally likely to have active MM, meaning this does not explain the racial differences seen.

Why treatment initiation increased over time 
Increases in treatment initiation likely reflect:

    • Faster and better diagnosis 
    • More effective and less toxic treatments 
    • Updated diagnostic criteria in 2014 that reclassified some patients as needing treatment

Important MM drugs such as bortezomib (FDA approved in 2003) and lenalidomide (approved in 2006) were already widely used throughout the study period.

Factors linked to delayed treatment 
Black patients were more likely to have characteristics associated with delayed treatment, including:

    • More medical conditions 
    • Less care at NCI-designated cancer centers 
    • Higher rates of poverty and low-income Medicare subsidies 
    • Living in the Southern U.S.

These findings suggest that social, economic, and healthcare access factors may play an important role.

Limitations 
The study focused only on older adults with Medicare, so results may not apply to younger patients or those with other insurance. Claims data can show what happened, but not why delays occurred.

Conclusion 
From 2007 to 2017, Black patients with multiple myeloma more likely experienced delayed treatment and less likely ever started treatment compared with White patients. These disparities have remained large and unchanged over time. Further research is needed to understand the causes and to develop interventions (such as patient navigation programs) to improve equity in MM care.

Reference: 
M. R. LeBlanc, X. Zhou, C. D. Baggett, et al., “Treatment Initiation Among Black and White Older Adults With Multiple Myeloma: A SEER-Medicare Analysis,” Cancer Medicine 15, no. 2 (2026): e71563, https://doi.org/10.1002/cam4.71563.

Past, Present, and Future of Dexamethasone in Multiple Myeloma and AL Amyloidosis — Journal of Clinical Oncology (January 2026)

Background 
Dexamethasone has been used for more than 50 years to treat plasma cell disorders, including multiple myeloma (MM) and light-chain (AL) amyloidosis. Many patients receive about 40 mg once weekly for long periods, sometimes months or years.  

Evidence of dose-related side effects 
However, growing evidence shows that this dose can cause dose-related side effects, such as cataracts and infections. Even short-term effects like insomnia and leg swelling can significantly reduce quality of life.

Over the past five years, clinical trials in MM have shown that steroid-sparing regimens (treatments that reduce or avoid dexamethasone) can be effective and are better tolerated.  

Dexamethasone: Benefits vs disadvantages 
In newly diagnosed MM, strong evidence supports planned discontinuation of dexamethasone after 1–2 cycles, especially in older or frail patients. During maintenance therapy, the risks of continuing dexamethasone generally outweigh the benefits.

In relapsed or refractory MM, randomized trials show that once-weekly dexamethasone can add benefit when used with two-drug (doublet) regimens, but its value in three-drug (triplet) or four-drug (quadruplet) regimens is unclear. Some data also suggest that long-term dexamethasone use may reduce patients’ ability to tolerate or benefit from later treatments after disease progression.

In AL amyloidosis, using dexamethasone 40 mg once weekly for 6 months appears excessive and may increase the risk of fluid overload. Dexamethasone is also often used as a premedication for CD38-targeted monoclonal antibodies, but evidence shows it is no longer needed after 1–2 cycles. For supportive care, much lower doses (4–8 mg as needed) are often sufficient.

Why this study matters 
Overall, despite long-standing use of corticosteroids in clinical trials and treatment guidelines, current evidence supports further study and broader use of corticosteroid-sparing approaches across plasma cell disorders.

Reference: 
Rahul Banerjee et al. Past, Present, and Future of Dexamethasone in Multiple Myeloma and AL Amyloidosis. J Clin Oncol 0, JCO-25-01713 DOI:10.1200/JCO-25-01713  

Epidemiology of Monoclonal Gammopathies in Sub-Saharan Africa: A Systematic Review and Meta-Analysis of MGUS and Multiple Myeloma — Tropical Medicine & International Health (January 2026)

Background 
Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) affect plasma cells. These conditions are known to be more common in people of African ancestry, but reliable data from Sub-Saharan Africa (SSA)—home to the world’s largest Black population—have been limited.

How was the study conducted? 
This study reviewed and combined results from 45 published studies from SSA (8 on MGUS and 37 on MM). The pooled prevalence of MGUS was 3.1% (95% CI: 0.8%–12.0%), while MM prevalence was 7.8% (95% CI: 5.6%–10.4%). MM was most common in Central Africa and least common in West Africa, whereas MGUS was most frequently reported in Southern Africa. The relatively low MGUS prevalence likely reflects underdiagnosis, as many people are only diagnosed once they develop symptomatic MM.

Survival outcomes for MM in SSA were poor. The pooled mean survival was 34.7 months, with 46.0% of patients alive at 1 year and 20.7% at 5 years—much lower than survival rates reported in high-income countries. Late diagnosis, limited access to diagnostic tests (such as serum protein electrophoresis, immunofixation, and serum free light-chain assays), shortages of specialist care, and restricted access to modern treatments and autologous stem cell transplantation (ASCT) are major contributors.

• HIV infection strongly affected outcomes. MM prevalence among people living with HIV was 7.2% (95% CI: 1.9%–24.2%). Survival was much shorter in HIV-positive patients (9.9 months) compared with HIV-negative patients (36.7 months). HIV was also associated with earlier disease onset and more aggressive disease.
• Kidney problems were common. About 30.1% (95% CI: 23.5%–37.6%) of MM patients had renal failure at diagnosis, a rate similar to high-income countries. However, in SSA this often occurs after long delays in diagnosis and in the setting of advanced disease.

Why this study matters 
Overall, MGUS and MM place a substantial and underrecognized burden on Sub-Saharan Africa, with much worse survival than global averages. The findings highlight an urgent need to improve early detection, strengthen diagnostic infrastructure, increase clinician awareness, and expand access to effective modern therapies. These steps are essential to improve outcomes and reduce inequities in myeloma care across the region.

Reference: 
I. S. Ojo, O. J. Badero, T. O. Oluwalana, et al., “Epidemiology of Monoclonal Gammopathies in Sub-Saharan Africa: A Systematic Review and Meta-Analysis of MGUS and Multiple Myeloma,” Tropical Medicine & International Health (2026): 1–17, https://doi.org/10.1111/tmi.70066.

Boosting CAR T-cell efficacy by blocking proteasomal degradation of membrane antigens. — Blood (January 2026)

Background 
CAR T-cell therapy targeting B-cell maturation antigen (BCMA) has shown high response rates in multiple myeloma. However, most patients eventually relapse. One major reason is that myeloma cells reduce or lose BCMA on their surface, making them harder for CAR T cells to recognize and kill.

Until now, ways to safely increase BCMA levels on tumor cells have been limited.  

Key points 
    • BCMA, an important target on multiple myeloma (MM) cells, is rapidly broken down by the ubiquitin–proteasome system (UPS) at the cell surface through a p97-dependent process. 
    • Proteasome inhibitors (PIs), especially carfilzomib (CFZ), increase BCMA levels on myeloma cells. 
    • Higher BCMA levels improve and can restore the activity of BCMA-directed CAR T cells, including in patients who have relapsed after CAR T-cell therapy

Main findings 
    • BCMA is a short-lived protein that is tagged with K48-linked ubiquitin chains at the plasma membrane and then degraded by the proteasome with the help of p97. 
    • This mechanism is unusual because most cell-surface proteins are regulated through different ubiquitin pathways and degraded in lysosomes, not directly by the proteasome. 
    • Blocking the proteasome with proteasome inhibitors (PIs) prevents BCMA degradation and raises BCMA levels on myeloma cells.

Effects of carfilzomib 
    • Carfilzomib (CFZ), an FDA- and EMA-approved PI for multiple myeloma, was identified as the most effective drug for stabilizing BCMA. 
    • CFZ increased BCMA expression and significantly improved BCMA CAR T-cell killing: 
           - In laboratory (in vitro) models 
           - In mouse (in vivo) models 
           - Against both PI-sensitive and PI-resistant myeloma cells 
    • CFZ did not harm T-cell viability, activity, or exhaustion.

Clinical evidence (CarCAR Protocol) 
    • 10 patients who had relapsed after BCMA CAR T-cell therapy were treated with CFZ under the CarCAR protocol. 
    • All patients showed increased BCMA expression on myeloma cells after CFZ treatment. 
    • Clinical responses occurred only in patients who still had residual or expanding CAR T cells, indicating that CFZ likely restored CAR T-cell function rather than acting alone.

Why this study matters 
    • Loss of BCMA due to genetic deletion is rare (4–7%), while relapse is common, suggesting that reversible protein degradation, not genetics, often drives resistance. 
    • CFZ targets a drug-modifiable mechanism, offering a practical way to overcome resistance. 
    • CFZ may be especially effective in the bone marrow, where the BCMA ligand APRIL promotes BCMA degradation—a process reversed by proteasome inhibition.

Clinical implications 
    • CFZ could be used to: restore activity of residual CAR T cells in relapsed or refractory (R/R) multiple myeloma; and enhance CAR T-cell efficacy upfront when given together with BCMA CAR T cells 
    • CFZ is already approved for MM, making clinical use feasible, though patient selection and side-effect risks must be considered. 
    • Results from this small cohort should be interpreted cautiously, and larger studies are needed. 
    • A national multicenter phase 2 clinical trial is being initiated by the German Multiple Myeloma Study Group.

Broader impact 
    • This study identifies proteasome-mediated degradation at the plasma membrane as a new way cells control surface proteins. 
    • The findings may apply not only to BCMA CAR T cells, but also to BCMA bispecific T-cell engagers and other immunotherapies targeting surface proteins

Conclusion 
BCMA levels on myeloma cells are controlled by p97-dependent proteasomal degradation at the cell surface. Carfilzomib (CFZ) blocks this process, increases BCMA expression, and enhances or restores BCMA CAR T-cell activity. These results support using CFZ both after relapse and potentially upfront with CAR T-cell therapy to improve outcomes for patients with multiple myeloma.

Reference: 
Leonie Rieger, Kilian Irlinger, Franziska Füchsl, Marlene Tietje, Anna Purcarea, Nicolas Barbian, Melanie Faber, Carolin Vogelsang, Lisa Pfeuffer, Sonja Stotz, Oleksandra Karpiuk, Tobias Schulze, Abirami Augsburger, Nadine Glaisner, Verena Konetzki, Sabrina Friedel, Andrej Besse, Lenka Besse, Christoph Driessen, Maike Buchner, Kristina Schwamborn, Katja Steiger, Piero Giansanti, Sebastian Theurich, Johannes Waldschmidt, K. Martin Kortüm, Michael Hudecek, Hermann Einsele, Marion Högner, Bernhard Kuster, Angela M. Krackhardt, Judith S. Hecker, Florian Bassermann; Boosting CAR T-cell efficacy by blocking proteasomal degradation of membrane antigens. Blood 2026; 147 (5): 534–546. doi: https://doi.org/10.1182/blood.2024027616

Addition of anti-CD38 mAb in newly diagnosed multiple myeloma: advancing toward quadruplet induction regimens — Blood Neoplasia (February 2026)

Background 
Adding CD38-targeted monoclonal antibodies (daratumumab or isatuximab) to initial (induction) treatment has improved outcomes for people with newly diagnosed multiple myeloma (NDMM). However, it has been unclear whether these benefits apply equally to patients with high-risk multiple myeloma (HRMM).

What is the purpose of the study? 
To address this, researchers reviewed and combined data from 11 randomized clinical trials involving 5,588 patients with NDMM, including 915 patients with high-risk disease. The trials compared standard induction treatments with or without anti-CD38 antibodies. Key outcomes were minimal residual disease (MRD) negativity (a very deep response to treatment) and progression-free survival (PFS) (how long patients lived without their disease worsening).

Main findings 
    • Anti-CD38 regimens more than doubled MRD-negative response rates in: 
            - Transplant-eligible (TE) patients (OR 2.32) 
            - Transplant-ineligible (TIE) patients (OR 3.26) 
    • Among TE patients, MRD-negativity improved in both: 
            - High-risk MM (OR 2.01) 
            - Standard-risk MM (OR 2.74) 
    • Anti-CD38 therapy significantly prolonged PFS in: 
            -TE patients (HR 0.52) 
            -TIE patients (HR 0.55) 
    • An overall survival benefit was observed in TIE patients. 
    • Benefits were consistent across cytogenetic risk groups and clinical subgroups.

Anti-CD38 treatment led to higher rates of serious infections and blood-related side effects, but these toxicities were generally manageable.

Key context and interpretation 
    • Daratumumab (given intravenously or subcutaneously) and isatuximab are monoclonal antibodies that target the CD38 protein on myeloma cells. 
    • The PERSEUS trial showed that subcutaneous daratumumab plus VRd (bortezomib, lenalidomide, dexamethasone) significantly improved MRD-negativity and PFS, including in high-risk patients. 
    • Across this analysis, daratumumab and isatuximab showed similar effectiveness for MRD-negativity and PFS, though only one study included isatuximab, so more trials are needed. 
    • High-risk disease in these trials was defined mainly by cytogenetic abnormalities, such as t(4;14), t(14;16), or del(17p). Newer 2025 International Myeloma Working Group criteria were not yet in use.

Importantly, patients with high-risk myeloma had a 17.0% higher MRD-negative rate with anti-CD38 therapy, and improved PFS similar to standard-risk patients.

Although anti-CD38 treatments increase upfront costs, achieving deeper and longer-lasting responses may reduce relapses, hospitalizations, and the need for later intensive treatments.

Limitations 
    • Trials mainly enrolled younger and fit patients, so results may not fully reflect older or frail populations. 
    • Definitions of high-risk disease and MRD testing methods varied between studies. 
    • Real-world access, cost, and applicability (especially in resource-limited settings) require further study.

Conclusion 
Adding anti-CD38 monoclonal antibodies to first-line treatment for newly diagnosed multiple myeloma leads to deeper responses and longer disease control, including in patients with high-risk disease, with acceptable side effects. These findings support the use of anti-CD38–based regimens as standard frontline therapy, while highlighting the need for future studies using updated risk definitions and real-world populations.

Reference: 
Yuqi Wang, Li Zhang, Dong He, Huan Chen, Hanzhen Zhang, Youhai Yuan, Cuilian Zhang, Ru Feng, Yongqiang Wei, Xiaolei Wei; Addition of anti-CD38 mAb in newly diagnosed multiple myeloma: advancing toward quadruplet induction regimens. Blood Neoplasia 2026; 3 (1): 100189. doi: https://doi.org/10.1016/j.bneo.2025.100189  

Composition and Functional State of T and NK Cells in the Extramedullary Myeloma Tumor Microenvironment — Blood Cancer Discovery (February 2026)

What is the purpose of the study? 
Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma that grows outside the bone marrow and is linked to resistance to modern immunotherapies and shorter survival. To better understand why EMM is hard to treat, researchers studied the immune cells in EMM tumors and compared them with those in the bone marrow (BM).

How was the study conducted? 
Using single-cell RNA sequencing, flow cytometry, and spatial transcriptomics, the study found major differences between the EMM tumor microenvironment (TME) and the BM. T cells and natural killer (NK) cells were the most common immune cells in EMM tumors. However, compared with the BM, EMM tumors had fewer immune cells relative to tumor cells, fewer CD4+ T cells, and a higher proportion of regulatory CD16− NK cells, which are less effective at killing cancer cells.

Key findings 
In about half of EMM tumors, there was a high number of exhausted but tumor-reactive CD8+ T cells, meaning these cells recognize cancer but are functionally weakened. These exhausted CD8+ T cells showed increased expression of immune checkpoint proteins such as PD-1. In addition, CD16− NK cells showed higher expression of the inhibitory receptor KLRC1 (NKG2A).

Why this study matters 
Overall, the findings suggest that the EMM tumor microenvironment suppresses immune function, particularly through less cytotoxic NK cells and exhaustion of CD8+ T cells. Direct cell–cell interactions within EMM tumors may contribute to this immune suppression and help explain why EMM responds poorly to current immunotherapies.

Reference: 
Anjana Anilkumar Sithara, Veronika Kapustova, David Zihala, Ondrej Venglar, Daniel Bilek, Moutaz Helal, Mara John, Eva Radova, Lucie Broskevicova, Jan Vrana, Gabriela Havlova, Ludmila Muronova, Tereza Popkova, Jana Mihalyova, Hana Plonkova, Serafim Nenarokov, Kamlesh Bisht, Hongfang Wang, Helgi Van de Velde, Sandra Charvatova, Ivo Demel, Michal Kascak, Milan Navratil, Martin Havel, Juli Bago, Michal Simicek, Angela Riedel, Leo Rasche, Tereza Sevcikova, Ola Landgren, Roman Hajek, Tomas Jelinek; Composition and Functional State of T and NK Cells in the Extramedullary Myeloma Tumor Microenvironment. Blood Cancer Discov 2026; https://doi.org/10.1158/2643-3230.BCD-25-0170

Daratumumab-based first-line therapy benefit multiple myeloma patients in a real-world setting: a multi-center retrospective propensity score-match study — Annals of Hematology (February 2026)

What is the purpose of the study? 
Multiple myeloma (MM) is still not curable. Achieving the deepest possible remission with the first treatment is important because later treatments are often less effective and more toxic. Clinical trials have shown that adding the antibody drug daratumumab to initial therapy improves outcomes in newly diagnosed multiple myeloma (NDMM). However, patients in the real-world setting (especially in developing countries) often differ from those in clinical trials and may receive fewer doses due to cost and access. This study examined whether daratumumab is still beneficial in real-world practice.

How the study was conducted 
Researchers analyzed 761 patients with newly diagnosed multiple myeloma treated in multiple centers across southern China between 2017 and 2023. 177 patients received daratumumab as part of first-line therapy, 584 patients received similar treatments without daratumumab.

To make fair comparisons, propensity score matching (PSM) was used, resulting in 158 daratumumab-treated patients and 278 matched control patients with similar disease stage, cytogenetic risk, and treatment regimens. Treatment responses were assessed using International Myeloma Working Group (IMWG) criteria, and measurable residual disease (MRD) was measured using next-generation flow cytometry.

Main results 
    • Compared with patients who did not receive daratumumab, those who did had: 
    • Deeper responses after induction therapy 
          - ≥ very good partial response: 85.0% vs. 61.3% 
          - MRD negativity: 73.0% vs. 51.9% 
    • Better long-term outcomes 
          - 3-year progression-free survival (PFS): 75.6% vs. 55.0%  [Hazard ratio (HR) 0.49, 95% CI 0.36–0.66]
          - Overall survival (OS): 78.3% vs. 74.4%  [HR 0.56, 95% CI 0.36–0.86 ]

These benefits remained consistent after PSM analysis.

Who benefited most 
    • Daratumumab improved PFS in patients with gain/amp(1q21) cytogenetic abnormality 
    • It did not significantly improve PFS in patients with del(17p) or t(4;14) 
    • Benefits were seen across many high-risk groups, including patients with advanced stage disease, renal impairment, and extramedullary disease (EMD) 
    • Adding daratumumab to the standard bortezomib/lenalidomide/dexamethasone (VRd) regimen (DVRd) improved PFS and OS compared with VRd alone

Why this study matters 
Unlike clinical trials such as ALCYONE, ICARIA-MM, and IKEMA, most patients in this real-world study received only limited courses of daratumumab, often stopping treatment once symptoms improved due to cost or insurance restrictions. Despite this, daratumumab still provided meaningful benefits. This suggests that early disease control and deeper initial remission are critical, even when continuous treatment is not possible.

Limitations 
This was a retrospective real-world study with varied treatment regimens and limited daratumumab exposure. The optimal number of daratumumab cycles was not assessed.

Conclusion 
In real-world clinical practice, daratumumab-based first-line therapy improves depth of remission, progression-free survival, and overall survival in newly diagnosed multiple myeloma, even when treatment duration is limited. Adding daratumumab (especially to the VRd regimen) can be considered a favorable option for first-line treatment outside of randomized clinical trials.

Reference: 
Wang, Y., Chen, X., Liang, Q. et al. Daratumumab-based first-line therapy benefit multiple myeloma patients in a real-world setting: a multi-center retrospective propensity score-match study. Ann Hematol 105, 87 (2026). https://doi.org/10.1007/s00277-026-06808-5

Single-Cell Multiomics Reveals Regulatory Mechanisms of CAR T Cell Persistence and Dysfunction in Multiple Myeloma — Blood Neoplasia (February 2026)

What is the purpose of the study? 
CAR T-cell therapy is an important treatment for multiple myeloma (MM), but in some patients, the CAR T cells do not last long enough or work as expected. To understand why, researchers studied BCMA-targeted CAR T cells from the bone marrow and blood of MM patients over time, using advanced single-cell analyses.

Key findings 
They found that CAR T cells in the bone marrow were more highly activated and more “exhausted” than those in the blood. Many of these cells failed to properly transition from short-lived “effector” cells into long-lasting “memory” cells. As a result, more CAR T cells became terminally differentiated, which was linked to poorer persistence of the therapy in the body.

In one patient who had only a partial response, the researchers identified a single CAR T-cell clone that expanded excessively and produced high levels of the anti-inflammatory cytokine IL-10. This IL-10 production increased when the cells were stimulated through both the CAR and the normal T-cell receptor (TCR). Higher IL-10 levels may have reduced CAR T-cell growth and survival, contributing to treatment failure.

Why this study matters 
Overall, the study identifies key biological mechanisms that limit CAR T-cell persistence in multiple myeloma and points to potential molecular targets to improve the durability and effectiveness of CAR T-cell therapy.

Reference: 
Lorea Jordana-Urriza, Guillermo Serrano, Sergio Camara-Peña, Maria E. Calleja-Cervantes, Patxi San Martin-Uriz, Aintzane Zabaleta, Aina Oliver-Caldes, Marta Español-Rego, Diego Alignani, Teresa Lozano, Saray Rodriguez-Diaz, Elena Iglesias, Valentin Cabañas, Juan L. Reguera, Veronica Gonzalez-Calle, Maria V. Mateos, Fermin Sanchez-Guijo, Bruno Paiva, Juan J. Lasarte, Susana Inoges, Ascension Lopez-Diaz de Cerio, Azucena Gonzalez-Navarro, Manel Juan, Carlos Fernandez de Larrea, Esteban Tamariz, Ana Alfonso-Pierola, Paula Rodriguez-Otero, Jesus San-Miguel, Mikel Hernaez, Juan R. Rodriguez-Madoz, Felipe Prosper; Single-Cell Multiomics Reveals Regulatory Mechanisms of CAR T Cell Persistence and Dysfunction in Multiple Myeloma. Blood Neoplasia 2026; 100203. doi: https://doi.org/10.1016/j.bneo.2026.100203

Complementary Roles of Next-Generation Flow and Next-Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma — Journal of Korean Medical Science (February 2026) 
 

What is the purpose of the study? 
Measurable residual disease (MRD) testing uses very sensitive methods to detect small numbers of remaining cancer cells after treatment in multiple myeloma (MM). MRD status helps predict prognosis and guide further therapy. Two advanced MRD methods are commonly used: next-generation flow cytometry (NGF-MRD) and next-generation sequencing (NGS-MRD). This study compared how well these two tests perform and how useful they are in clinical care.

How was the study conducted? 
The study analyzed 55 bone marrow samples from 41 patients with multiple myeloma. 
    • NGF-MRD was performed on fresh bone marrow samples using EuroFlow protocols. 
    • NGS-MRD was performed on stored DNA using the LymphoTrack® IGH FR1 assay.

Results 
    • MRD was detected in 43.6% of samples using NGF-MRD and 29.1% using NGS-MRD. 
    • The two methods agreed in 67.3% of cases, showing a moderate correlation (ρ = 0.506). 
    • At 3 years, progression-free survival (PFS) was: 
          - 37.5% for NGF-MRD–positive vs 71.6% for NGF-MRD–negative patients 
          - 40.4% for NGS-MRD–positive vs 69.1% for NGS-MRD–negative patients (neither comparison reached statistical significance alone). 
    • When both MRD tests were combined, outcomes were clearer: 
          - Patients positive by either NGF or NGS had a 3-year PFS of 40.0% 
          - Patients negative by both tests had a 3-year PFS of 75.9% (P = 0.035).

Revised International Staging System (R-ISS) stage III (hazard ratio [HR] 3.30) and combined MRD positivity (HR 3.01) were the strongest predictors of disease progression.

MRD testing is well established in blood cancers such as B-cell acute lymphoblastic leukemia (B-ALL), where flow-based and sequencing-based methods are complementary. This study shows a similar pattern in multiple myeloma.  

Compared with previous studies, the agreement between NGF and NGS was lower, mainly due to more cases where NGF detected MRD but NGS did not. This was likely related to lower DNA input and lower sequencing sensitivity in the NGS assay.

The two tests detect disease differently: 
    • NGF-MRD identifies abnormal living plasma cells. 
    • NGS-MRD detects cancer-specific immunoglobulin gene rearrangements (IGH, and potentially IGK or IGL) at the DNA level.

MRD testing was also informative in patients who had not achieved complete response (CR), such as those in very good partial response (VGPR) or partial response (PR). This may be because blood markers like monoclonal protein decline slowly and can lag behind true disease clearance.

Patients who were MRD-positive by either test had a higher risk of disease progression, including those with discordant results (positive by only one method). This highlights the complementary value of using both NGF and NGS rather than relying on a single assay.

Limitations 
    • MRD testing was performed at different treatment stages (post-transplant, during maintenance, or after relapse). 
    • NGS sensitivity may have been underestimated because testing was not repeated on negative samples and relied on single-read detection. 
    • The study included a relatively small number of patients.

Why this study matters 
Both NGF-MRD and NGS-MRD provide important and complementary information for monitoring minimal residual disease in multiple myeloma. Even MRD detected by only one method was associated with worse outcomes. Combining both approaches improves risk assessment and may better guide personalized treatment decisions. Larger studies with standardized testing schedules and optimized laboratory methods are needed to further refine MRD-guided care in MM.

Reference: 
Park MS, Lim DJ, Kim HJ, Cho D, Yoon SE, Kim SJ, Kim K, Kim HY. Complementary Roles of Next-Generation Flow and Next-Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma. J Korean Med Sci. 2025 Sep;41(6):e5. https://doi.org/10.3346/jkms.2026.41.e5

High-throughput monoclonal gammopathy community monitoring programme — British Journal of Haematology (February 2026)

Background 
Monoclonal gammopathy (MG) is a common condition, affecting about 4.5% of adults over age 50. Each year, about 1% of people with MG progress to multiple myeloma (MM). Regular monitoring can help detect cancer earlier and improve outcomes.

However, most people with newly diagnosed MG are at low risk and are unlikely to develop cancer. Monitoring all patients in hospital clinics is inefficient and strains healthcare systems. A better system is needed to safely monitor most patients in the community while ensuring higher-risk patients receive specialist care.

The OxCOM Monitoring Program 
The Oxford Community MG Monitoring Program (OxCOM) is a risk-adapted community monitoring system developed in the Thames Valley (UK). It ran prospectively for 24 months (March 2021–March 2023) and covered a population of 2.5 million people.

The program included patients with newly discovered incidental MG (iMG)—meaning MG found during testing for other reasons.

How OxCOM works 
Patients were classified into: 
    • Low risk (75%) 
    • Intermediate risk (16%) 
    • High risk (9%)

Risk assessment used expert criteria, automated laboratory systems, and specialist review.

Follow-up was matched to risk: 
    • Low risk (OxCOM Remote): Blood tests every 4–12 months in primary care (no routine clinic visit). 
    • Intermediate risk (OxCOM Telemed): Blood tests plus virtual telephone clinic review in secondary care. 
    • High risk (OxCOM F2F): Urgent face-to-face haematology assessment (usually within 2 weeks).

The program required minimal extra staffing (one additional laboratory administrative role).

Who was monitored? 
Over the 2-year period, 1,290 patients with incidental monoclonal gammopathy (iMG) were identified. Of these, 962 (75%) were classified as low risk, 200 (16%) as intermediate risk, and 128 (9%) as high risk. The median age was 75 years, and 50% of patients were female.  

Common reasons for testing included anemia, bone pain, and fractures, which were more frequent in intermediate- and high-risk patients.

Did higher-risk patients receive more care? 
High-risk patients were much more likely to receive:

    • Face-to-face review (98%) 
    • Consultant hematologist assessment (68%) 
    • CT/MRI scans (86%) 
    • Bone marrow biopsy (59%) 
    • Multidisciplinary team (MDT) discussion (63%)

This shows that OxCOM successfully directed more specialist resources to patients at higher risk.

Did monitoring improve follow-up? 
Under OxCOM, follow-up monitoring improved substantially compared with 2019 (before the program was introduced). Among low-risk patients, 90% received repeat monitoring within the recommended time frame, compared with only 37% in 2019. For intermediate-risk patients, 84% received appropriate follow-up under OxCOM, compared with 77% previously. Among high-risk patients, 94% received timely follow-up under OxCOM, compared with 75% in 2019.

Overall, OxCOM markedly improved monitoring rates—especially for low-risk patients, who had previously been much more likely to miss follow-up testing.

Cancer diagnoses during follow-up 
After a median follow-up of 12.2 months, 48 patients (4%) were diagnosed with blood cancer.  

These included 34 patients with multiple myeloma, amyloidosis, or Waldenström macroglobulinaemia (WM) requiring treatment, and 11 patients with lymphoma. In addition, 37 patients (3%) were diagnosed with smoldering myeloma or WM, which did not require immediate treatment and were monitored.

Cancer diagnosis rates differed by risk group: 1% in low-risk patients, 5% in intermediate-risk patients, and 23% in high-risk patients. Importantly, 96% of cancers were diagnosed in outpatient settings rather than during emergency hospital admissions. This suggests that OxCOM did not delay diagnosis and appears to be a safe monitoring approach.

What types of cancer were detected? 
    • Most multiple myeloma cases (22/26) were detected through OxCOM monitoring. 
    • Most lymphoma cases (7/11) were diagnosed outside OxCOM, often after imaging for other reasons. 
    • In high-risk patients, 83% of cancers were detected through OxCOM review.

OxCOM was especially effective at detecting plasma cell disorders (like multiple myeloma), where changes in paraprotein levels closely reflect disease activity.

Why this matters  
An estimated 1.3 million adults in the UK may have incidental MG. Monitoring all patients in hospital clinics is not sustainable.

OxCOM shows that: 
    • Most low-risk patients can be safely monitored in primary care. 
    • Higher-risk patients receive a timely specialist review. 
    • Follow-up rates improve dramatically. 
    • Cancer detection remains safe and effective. 
    • Healthcare resources are used more efficiently.

Limitations 
    • Follow-up data is limited to 2 years. 
    • Comparisons with 2019 data were retrospective. 
    • Some aspects of repeat testing (e.g., early repeat testing for certain IgG patients) were not fully implemented.

Longer follow-up will clarify long-term benefits.

Conclusion 
OxCOM demonstrates that a risk-adapted, high-throughput monitoring system for incidental MG (iMG) is feasible, safe, low cost, efficient, effective at improving follow-up, and appropriate in directing care based on risk.

This model could support sustainable monitoring not only for MG but also for other early or precursor conditions.

Reference: 
Agarwal, G., Campbell, L., Carty, O., Larham, J., Knight, E., Moore, S., Gooding, S., Kothari, J., Browning, J., Evans, J., Ferguson, L., Vieira, A., Swanborough, L., Roberts, P., Bateman, E., Sadler, R. and Ramasamy, K. (2026), High-throughput monoclonal gammopathy community monitoring programme. Br J Haematol. https://doi.org/10.1111/bjh.70366

Enhancing the Safety of Ciltacabtagene Autoleucel in Relapsed Multiple Myeloma (MM): Identification of Potentially Modifiable Risk-Factors Associated with Delayed Neurotoxicity and Non-Relapse Mortality — Transplantation and Cellular Therapy (February 2026)

Background 
Ciltacabtagene autoleucel (cilta-cel) is a highly effective CAR-T cell therapy for relapsed multiple myeloma (MM). However, some patients develop serious delayed side effects affecting the nervous system (called delayed neurotoxicity, or DNT), including Parkinsonism, and some die from causes unrelated to myeloma relapse (non-relapse mortality, NRM). Understanding which patients are at higher risk may help improve safety and treatment decisions.

How was the study conducted? 
This was a large, multi-center retrospective study conducted by the US MM Immunotherapy Consortium. It included 761 patients treated with standard-of-care cilta-cel at 15 U.S. centers between May 2022 and December 2024. Researchers analyzed factors associated with DNT (especially Parkinsonism) and NRM.

Patient characteristics and treatment outcomes 
    • Median age: 65 years (range 30–88) 
    • Median prior lines of therapy: 5 
    • Cilta-cel used earlier (1–3 prior therapies) in 16% 
    • 39% had high-risk cytogenetics; 27% had extramedullary disease 
    • 86% received bridging therapy before CAR-T; 33% responded 
    • Median follow-up: 10.1 months 
    • Overall response rate: 92% 
    • Complete response (CR) rate: 70%

Delayed neurotoxicity (DNT) 
    • Occurred in 10% of patients. Patients who did not respond to bridging therapy had a higher risk of DNT, especially Parkinsonism. 
    • Parkinsonism occurred in 5% of non-responders vs 0.5% of responders 
    • Of 22 patients with Parkinsonism, 95% did not respond to bridging therapy, even though most later responded to CAR-T

Role of lymphocyte count 
Higher peak absolute lymphocyte count (ALC) after treatment was strongly linked to Parkinsonism.

Non-relapse mortality (NRM) 
    • NRM was 9% at 1 year and 10% at 2 years 
    • Main causes of NRM: 
          - Infections (56%) 
          - Immune-mediated acute adverse events (22%) 
          - Delayed toxicities such as DNT and colitis (9.5%) 
          - Second cancers (8%)

Independent predictors of higher NRM included: 
    • No response to bridging therapy 
    • Poor performance status (≥2) 
    • High-risk cytogenetics 
    • Age ≥70 years

Conclusions 
This large real-world study identified modifiable risk factors for serious neurologic toxicity and non-relapse death after cilta-cel. Lack of response to bridging therapy and high peak ALC (>3000/µL) were strongly associated with Parkinsonism. Peak ALC may serve as a useful biomarker to identify patients at higher risk, and improving bridging strategies may help reduce both neurologic toxicity and non-relapse mortality in patients receiving cilta-cel.

Reference: 
Sidana, Surbhi et al. Enhancing the Safety of Ciltacabtagene Autoleucel in Relapsed Multiple Myeloma (MM): Identification of Potentially Modifiable Risk-Factors Associated with Delayed Neurotoxicity and Non-Relapse Mortality. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 32, Issue 2, S11 – S12 February 2026.

Belantamab mafodotin does not induce B-cell maturation antigen loss or systemic immune dysfunction in multiple myeloma — Haematologica (February 2026)

Background 
Several types of treatments for multiple myeloma (MM) target a protein on myeloma cells called B-cell maturation antigen (BCMA). These include chimeric antigen receptor (CAR) T-cell therapies, bispecific antibodies (bsAb), and antibody–drug conjugates (ADC).  

While CAR T-cell and bsAb therapies can be very effective, their success may be reduced over time because immune cells become exhausted or because myeloma cells reduce or change their BCMA expression. This makes the order (sequencing) in which BCMA-targeting treatments are given an important clinical question.

What is the purpose of the study? 
This analysis examined data from multiple DREAMM clinical trials of the ADC belantamab mafodotin, given alone or in combination regimens, to determine whether it affects BCMA levels or immune cell health in ways that could limit later treatment with CAR T-cell or bsAb therapies.

Key findings

    • BCMA target preservation. Levels of soluble BCMA (sBCMA) in the blood decreased at best confirmed response, likely reflecting tumor reduction, and returned close to baseline when disease progressed. Importantly, belantamab mafodotin continued to bind BCMA throughout treatment, including at progression, indicating that BCMA was not lost or permanently altered. This suggests that other BCMA-targeting therapies should still be able to bind BCMA after belantamab mafodotin treatment.

    • No evidence of harmful immune effects. Belantamab mafodotin did not significantly reduce T-cell or natural killer (NK) cell counts, nor did it increase most markers of T-cell exhaustion (PD-1, TIGIT, TIM-3 [except on NK cells], or CTLA-4). Markers of immune activation, proliferation (Ki67), and antitumor function (granzyme B, CD107a) were preserved. The CD4+/CD8+ T-cell ratio, which is important for CAR T-cell therapy success, was also unchanged.

    • Implications for treatment sequencing: Unlike some BCMA-directed T-cell–engaging therapies, belantamab mafodotin did not appear to cause BCMA loss or long-term immune exhaustion. These findings suggest it may be suitable for use before CAR T-cell or bsAb therapies without reducing their effectiveness, although confirmatory prospective studies are needed.

    • Clinical trial outcomes: Combination regimens containing belantamab mafodotin showed strong clinical benefits in later-line settings. 
          - DREAMM-7: BVd (belantamab mafodotin, bortezomib, dexamethasone) improved progression-free survival (PFS) by 23 months versus daratumumab-based therapy and showed overall survival benefit. 
          - DREAMM-8: BPd (belantamab mafodotin, pomalidomide, dexamethasone) significantly improved PFS versus PVd, with benefits maintained into the next line of therapy.

    • Subsequent BCMA therapy outcomes: Limited follow-up data suggest that patients treated with bispecific antibodies (including teclistamab) after belantamab mafodotin can still achieve outcomes similar to those seen in patients without prior BCMA therapy. However, these data are based on small and heterogeneous patient groups.

Limitations 
Some analyses included small patient numbers, used data from different trials and treatment schedules, and limited samples at disease progression. Longer follow-up and larger, prospective studies are needed.

Conclusion 
Across multiple studies, belantamab mafodotin did not impair BCMA expression, BCMA binding, or immune cell health. These results support the possibility that belantamab mafodotin can be used as an early BCMA-targeting therapy in multiple myeloma without compromising later treatment options, though further clinical studies are required to confirm this strategy.

Reference: 
Musa H, Mielnik M, Trudel S, Weisel K, Mockus-Daehn T, Ferron-Brady G, Hong Q, Ma Y, Patel S, Suchindran S, Zhou X, Richardson PG, Cohen AD, Lowther DE. Belantamab mafodotin does not induce B-cell maturation antigen loss or systemic immune dysfunction in multiple myeloma. Haematologica 2026;111(2):665-678; https://doi.org/10.3324/haematol.2025.288203.

Use of upfront autologous stem cell transplantation in myeloma patients aged > 65 years: a population-based study by the Nordic Myeloma Study Group — Haematologica (February 2026)

Background 
More people aged over 65 are now being treated with autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM). It has been unclear whether this change is due to an aging population or a true shift in medical practice. Recent randomized clinical trials in patients aged ≤65 years showed that ASCT improves progression-free survival, and one trial also showed a benefit in overall survival (OS). These findings raised questions about whether ASCT could also benefit older patients.

What is the purpose of the study?  
This large, real-world study examined how often ASCT is used in patients older than 65 years and whether it is safe and effective in these age groups. The study included 12,369 NDMM patients aged 18–75 years diagnosed between 2008 and 2020 in Nordic and Baltic countries, using national cancer and myeloma registries and hospital records. Patients were followed until the end of 2021. Patients older than 75 years were excluded.

Use of ASCT by age 
    • Among patients aged 18–65 years, about 70% received ASCT, and this rate stayed stable over time. 
    • In patients aged 66–70 years, ASCT use increased 2.7-fold, from 16% in 2008 to 37% in 2015–2020. 
    • Only 1.8% of patients aged 71–75 years received ASCT, with no clear increase over time.

Treatments before ASCT 
    • Over 90% of patients received modern treatments such as proteasome inhibitors and/or immunomodulatory drugs before ASCT. 
    • Only 1% received daratumumab-based induction therapy, reflecting treatment practices during much of the study period.

Effectiveness and safety 
    • The proportion of patients achieving a very good partial response (VGPR) or better was similar across all age groups. 
    • Overall survival at 5 years was: 
           - 68.7% for ages 18–65 
           - 66.8% for ages 66–70 
           - 57.1% for ages 71–75 (with wide confidence intervals due to small numbers) 
    • Survival outcomes for patients aged 66–70 years were comparable to younger patients. 
    • 100-day mortality after ASCT was low (0.9%), with no significant difference by age.

Patients with standard-risk cytogenetics (based on FISH, per IMWG criteria) had better survival than those with high-risk FISH, regardless of age.

Key conclusions 
    • In real-world clinical practice, ASCT is increasingly used in selected patients aged 66–70 years. 
    • For these patients, ASCT is as safe and effective as in younger patients. 
    • These findings support results from prior studies and meta-analyses and align with recent clinical trials.

Future directions 
New treatment strategies—such as quadruplet regimens including CD38 antibodies, CAR T-cell therapy (e.g., CARTITUDE-6), and bispecific antibodies—are being studied and may further change the role of ASCT. More population-based studies are needed to confirm how these approaches perform outside clinical trials.

Implications 
As populations age and older patients remain fit, these results support offering upfront ASCT to selected patients up to age 70 and potentially beyond, rather than excluding patients based on age alone. The study recommends that future randomized trials should not exclude patients solely because of age.

Reference: 
Moore KLF, Rognvaldsson S, Szabo AG, Vaitekėnaitė V, Loigom D, Genell A, Thorsen J, Norgaard JN, Thorsteinsdottir S, Knut-Bojanowska D, Lysen A, Schjesvold F, Peceliunas V, Kaare A, Palk K, Parnat M, Sigurdsson A, Vangsted AJ, Blimark CH, Study Group NM. Use of upfront autologous stem cell transplantation in myeloma patients aged > 65 years: a population-based study by the Nordic Myeloma Study Group. Haematologica 2026;111(2):693-697; https://doi.org/10.3324/haematol.2025.287344.  

Clinical Trials

Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma — Annals of Hematology (January 2026)

Background 
Plitidepsin (P) is an anticancer drug originally derived from a marine organism. In the phase III ADMYRE clinical trial, plitidepsin combined with low-dose dexamethasone (LD-DXM) was tested in people with relapsed or refractory multiple myeloma (RRMM).  

Because there was no direct randomized trial comparing plitidepsin + LD-DXM with pomalidomide (POM) + LD-DXM, researchers performed a detailed comparison using individual patient data from similar, contemporary studies. These pomalidomide studies served as an External Control Arm (ECA).

What was compared 
    •    ECA1: Plitidepsin + LD-DXM (from ADMYRE) vs. POM + LD-DXM 
    •    ECA2: POM + LD-DXM vs. LD-DXM alone (the control arm in ADMYRE)

The main outcome was overall survival (OS). Safety was assessed by treatment-related adverse events (TRAEs). Progression-free survival (PFS) was not compared because the trials used different rules to define disease progression, which would make results unreliable.

Key results

    • Overall survival: Plitidepsin + LD-DXM was non-inferior (not worse) than POM + LD-DXM. 
          - Median OS: 11.8 vs. 13.9 months
          - Hazard ratio (HR): 1.009 (95% CI 0.812–1.254; p = 0.9336)

    • The survival benefit of POM + LD-DXM compared with LD-DXM alone (HR 0.762) was similar to the benefit previously seen for plitidepsin + LD-DXM vs. LD-DXM in ADMYRE (HR 0.797).

Safety
1. Plitidepsin + LD-DXM caused fewer serious blood-related side effects and infections than POM + LD-DXM:

    •    Severe neutropenia: 2.5% vs. 37.1% 
    •    Severe thrombocytopenia: 2.5% vs. 13.2% 
    •    Infections: 8.1% vs. 18.7%

2. Plitidepsin + LD-DXM had more gastrointestinal symptoms, muscle pain, and increases in blood creatine phosphokinase, but these side effects were generally different rather than more dangerous. 
3. As expected, combination treatments (either plitidepsin or pomalidomide with LD-DXM) caused more side effects than LD-DXM alone.

Why this study matters 
Plitidepsin works in a new way, targeting eEF1A2, a protein overexpressed in multiple myeloma and not targeted by other modern myeloma drugs. Its safety profile differs from many current treatments and is notable for low rates of blood toxicity and infections, which may be important for patients at higher risk of these complications.

Conclusion 
This patient-level comparison shows that plitidepsin + low-dose dexamethasone provides overall survival similar to pomalidomide + low-dose dexamethasone, with fewer serious blood-related side effects and infections. Together with the progression-free survival benefit shown in the ADMYRE trial, these findings support plitidepsin as a valuable new treatment option for patients with relapsed or refractory multiple myeloma.

Reference: 
Ludwig, H., Terpos, E., Boccadoro, M. et al. Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma. Ann Hematol 105, 26 (2026). https://doi.org/10.1007/s00277-026-06811-w  

Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone — Blood (January 2026)

What is the purpose of the study? 
Circulating tumor cells (CTCs) are myeloma cells that can be found in the blood. In newly diagnosed multiple myeloma (NDMM), higher CTC levels are linked to higher risk of disease progression. This study examined whether CTC levels predict outcomes in transplant-eligible (TE) patients treated in phase 3 PERSEUS (EMN017) trial.

How was the study conducted? 
In PERSEUS, patients received either: 

• daratumumab/bortezomib/lenalidomide/dexamethasone (D-VRd) followed by daratumumab/lenalidomide maintenance 
• bortezomib/lenalidomide/dexamethasone (VRd) followed by lenalidomide maintenance, with autologous stem cell transplant (ASCT).  

Blood samples from 451 patients were analyzed for CTCs using flow cytometry.

Key findings

• CTCs were detected in 82% of patients. Higher CTC levels were independently associated with worse progression-free survival (PFS), even after accounting for other known risk factors. Patients with CTC-high disease (≥0.175%) had poorer outcomes than those with CTC-low disease.
• Treatment with D-VRd led to deeper and more frequent responses than VRd in both CTC-high and CTC-low patients. Rates of minimal residual disease (MRD) negativity were consistently higher with D-VRd at both sensitivity levels tested (10⁻⁵ and 10⁻⁶). For example, among CTC-high patients, MRD negativity at 10⁻⁶ was 47.2% with D-VRd vs 21.2% with VRd.
• D-VRd significantly improved PFS compared with VRd in CTC-low patients (4-year PFS: 88% vs 74%). In CTC-high patients, D-VRd showed a favorable trend toward improved PFS, but this did not reach statistical significance at the current follow-up.

Importantly, achieving sustained MRD negativity at 10⁻⁶ for at least 12 months was associated with similar outcomes regardless of baseline CTC level. This suggests that deep and durable responses can reduce the negative impact of high CTC levels at diagnosis.

Why this study matters 
Overall, this sub-study of PERSEUS shows that CTC levels are an independent prognostic factor in transplant-eligible NDMM. D-VRd improves response depth and MRD negativity across all CTC levels and improves PFS in CTC-low patients, with encouraging trends in CTC-high patients. These findings support measuring CTCs at diagnosis to help assess patient risk, while further research is needed to define standardized clinical thresholds.

Reference: 
Luca Bertamini, Cathelijne Fokkema, Paula Rodriguez-Otero, Mark van Duin, Evangelos Terpos, Mattia D’Agostino, Vincent H. J. van der Velden, Niels W. C. J. van de Donk, Michel Delforge, Christoph Driessen, Roman Hajek, Hermann Einsele, Annette Vangsted, Diego Vieyra, Ricardo Attar, Anna Sitthi-Amorn, Robin Carson, Fredrik Schjesvold, Pawel Robak, Meral Beksac, Andrew Spencer, Annemiek Broijl, Tom Cupedo, Philippe Moreau, Mario Boccadoro, Pieter Sonneveld; Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone. Blood 2026; 147 (4): 431–442. doi: https://doi.org/10.1182/blood.2025030113

Long-term follow-up of zevor-cel in patients with relapsed/refractory multiple myeloma — Blood Advances (January 2026)

What is the purpose of the study? 
People with relapsed or refractory multiple myeloma (RRMM) often stop responding to available treatments. This study evaluated zevorcabtagene autoleucel (zevor-cel, also called CT053), a BCMA-targeted CAR T-cell therapy, to see how safe and effective it is over long-term follow-up.

How was the study conducted?

    • LUMMICAR study 1, phase 1, open-label, single-arm trial 
    • Conducted in China 
    • 14 patients with RRMM who had received ≥3 prior treatments 
    • Patients received a single infusion of zevor-cel 
    • Median follow-up: 53.3 months (about 5 years)

Effectiveness results

    • Objective response rate (ORR): 100% 
    • 78.6% of patients achieved a complete response or better (CR/sCR) 
    • 92.9% achieved a very good partial response (VGPR) or better 
    • Median duration of response: 24.94 months 
    • Responses lasting: 
          - ≥36 months: 41.7% 
          - ≥48 months: 15.6% 
    • Overall survival rates: 
          - 24 months: 100% 
         - 36 months: 92.3% 
         - 48 months: 84.6% 
         - 60 months: 76.9% 
    • Median overall survival had not yet been reached at the time of analysis.

Minimal residual disease (MRD) negativity was seen in 92.3% of evaluable patients, including all patients with complete responses.

Safety results

    • No grade 3 or higher cytokine release syndrome (CRS) 
    • No neurotoxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS) 
    • Most CRS events were mild (grade 1–2) 
    • No delayed serious side effects, including: 
          - No second cancers 
          - No autoimmune diseases 
          - No delayed neurologic events 
    • No deaths were related to zevor-cel

Overall, side effects were mainly blood-related and manageable.

How zevor-cel compares to other CAR T therapies 
While direct comparisons are limited, the response rates with zevor-cel were:

    • Higher than reported for ide-cel (ORR 73%, CR or better 33%) 
    • Similar to cilta-cel phase 1 results (ORR 97%, CR 67%) 
    • Comparable to other China-based BCMA CAR T studies, such as CT103A and FUMANBA-1 (equecabtagene autoleucel)

Importantly, no patients required bridging therapy, which may have influenced outcomes.

Key takeaway 
After about 5 years of follow-up, zevor-cel showed durable and deep responses with an excellent safety profile in heavily pretreated patients with RRMM. No severe CRS, neurotoxicity, or delayed serious side effects were observed. While the study is small, these results support continued evaluation of zevor-cel in larger phase 2 trials, including the LUMMICAR study 2 in the United States and Canada.

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 2026; 10 (2): 468–478. doi: https://doi.org/10.1182/bloodadvances.2025017365

Target antigen and plasma cell phenotype are critical factors for sensitivity to response-adapted daratumumab therapy — Blood (January 2026)

Background 
This clinical trial studied daratumumab alone as an initial treatment for older patients with newly diagnosed multiple myeloma (MM) who were not eligible for stem cell transplant. The goal was to adjust treatment based on how well each patient responded.

How was the study conducted? 
After 2 treatment cycles, patients who showed a partial response or better continued daratumumab monotherapy. Patients with less response had lenalidomide or bortezomib added. Using this response-adapted approach, 97% of patients responded to treatment, side effects were generally low, and 37% of patients were able to stay on daratumumab alone.

Key findings 
Patients who responded well to daratumumab alone tended to have higher CD38 expression, a more mature plasma cell phenotype, and a more active immune tumor microenvironment (iTME). In contrast, patients who needed additional drugs showed lower CD38 expression, increased activity of adhesion pathways, tumor necrosis factor (TNF) signaling, KRAS signaling, and B-cell–related programs, along with a more immunosuppressed iTME.

The study also tracked how myeloma cells changed over time. Even after just 2 cycles of daratumumab, resistant tumor subclones began to expand. At relapse, daratumumab-resistant disease was driven by preexisting minor subclones with low CD38 expression, a pre–plasma cell phenotype, and ongoing resistance programs, suggesting that resistance develops through changes in tumor cell behavior rather than entirely new mutations.

Why this study matters 
Overall, this trial shows that response-adapted daratumumab therapy is safe and effective in older, transplant-ineligible patients with newly diagnosed MM. It identifies key biomarkers (including CD38 expression, plasma cell phenotype, and immune microenvironment features) that may help predict who can benefit from single-agent daratumumab.  

Reference: 
Mark B. Meads, Xiaohong Zhao, David Noyes, Praneeth R. Sudalagunta, Alexandra Achille, Chaomei Zhang, Rafael R. Canevarolo, Maria Silva, Dario Magaletti, Daniel DeAvila, Sonila Toska, Ashley Oates, Daniel Lastorino, Dietrich Werner Idiaquez, Jinming Song, Samer S. Sansil, Sean J. Yoder, Ariel F. Grajales-Cruz, Brandon Blue, Ciara L. Freeman, Jongphil Kim, Melissa Alsina, Jason Brayer, Ariosto S. Silva, Xiaofei Song, Kenneth H. Shain, Rachid Baz; Target antigen and plasma cell phenotype are critical factors for sensitivity to response-adapted daratumumab therapy. Blood 2026; 147 (5): 497–512. doi: https://doi.org/10.1182/blood.2025029921

Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma with 2–4 Prior Lines of Therapy: Updated Matching-Adjusted Indirect Comparison — Advances in Therapy (February 2026)

What is the purpose of the study? 
This study compared two CAR T-cell therapies, ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), for patients with relapsed/refractory multiple myeloma (RRMM) who had previously received 2–4 lines of therapy and were triple-class exposed (prior exposure to proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies).

Because there is no direct head-to-head clinical trial, researchers used a statistical method called an unanchored matching-adjusted indirect comparison (MAIC). This analysis used individual patient data from CARTITUDE-4 and CARTITUDE-1 (cilta-cel) and compared outcomes with published results from KarMMa-3 (ide-cel). Patient characteristics were carefully adjusted to make the comparison as fair as possible.

Key results 
After adjustment, cilta-cel showed significantly better outcomes than ide-cel:

    • Progression-free survival (PFS):  58% lower risk of disease progression or death 
    • Overall survival (OS):  42% lower risk of death 
    • Overall response rate:  Higher likelihood of response 
    • Deeper responses: 
          - ≥ Very good partial response (VGPR): RR 1.37 (p = 0.0009) 
          - ≥ Complete response (CR): RR 1.80 (p < 0.0001)

The improvement in PFS met criteria for clinically meaningful benefits based on European Society for Medical Oncology (ESMO) guidelines.

Why this study matters 
This updated analysis included longer follow-up data, allowing researchers to evaluate overall survival, which was not available in earlier comparisons. The findings confirm and extend prior results, showing that cilta-cel provides superior disease control and survival benefits compared with ide-cel in this difficult-to-treat patient population.

Important considerations 
    • MAIC analyses are widely used when direct clinical trials are not available, including health technology assessments. 
    • While careful adjustments were made, unmeasured differences between trials cannot be completely ruled out. 
    • Multiple sensitivity and bias analyses showed that the results were robust and unlikely to be explained by hidden confounding factors.

Conclusion 
Using longer-term data from CARTITUDE-1, CARTITUDE-4, and KarMMa-3, this updated MAIC demonstrates that cilta-cel is associated with significantly better progression-free survival, overall survival, and response rates than ide-cel in patients with triple-class exposed RRMM treated with 2–4 prior lines of therapy. These results strengthen the evidence supporting cilta-cel as a highly effective CAR T-cell therapy for this patient population.

Reference: 
Lopez-Muñoz, N., Bar, N., Diels, J. et al. Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma with 2–4 Prior Lines of Therapy: Updated Matching-Adjusted Indirect Comparison. Adv Ther (2026). https://doi.org/10.1007/s12325-025-03479-y

An oBservational retrospective Analysis of treatment patternS and Effectiveness of standard of CAre for Multiple Myeloma patients exposed to lenalidomide and a Proteasome inhibitor: BasecaMMp study — Clinical Lymphoma Myeloma and Leukemia (February 2026)

Background 
Multiple myeloma (MM) is the second most common blood cancer in Europe. Although many treatments are available, most patients eventually relapse or stop responding to standard therapies. This is especially challenging for patients whose disease no longer responds to lenalidomide (LEN) and proteasome inhibitors (PIs), two cornerstone treatments.

What is the purpose of the study? 
This real-world study examined how patients with relapsed or refractory multiple myeloma (RRMM) are treated in Germany after they have already received LEN and a PI, and how well these treatments work in routine clinical practice.

How was the study conducted? 
The BasecaMMp cohort included 1,834 RRMM patients treated in Germany between May 2016 and December 2023. All patients had previously received LEN and a PI within their first three lines of therapy.  

Researchers analyzed:

    • Treatment patterns after LEN and PI 
    • Progression-free survival (PFS) 
    • Overall survival (OS) 
    • Time to next treatment (TTNT)

Key findings

    • Patients were older (median age 72.5 years) and had already received a median of two prior lines of therapy. 
    • Nearly 48% were refractory to lenalidomide, and about 30% were double-refractory (refractory to both LEN and a PI). 
    • Treatments given after LEN and PI were highly diverse, with no single regimen used in more than 20% of patients—showing a lack of a clear standard of care.

Clinical outcomes were poor: 
    • Median PFS was 12.7 months overall and 11.3 months in LEN-refractory patients. 
    • Median OS was 37.1 months overall and 34.3 months in LEN-refractory patients.

How these results compare to other studies 
    • Outcomes were similar to those seen in daratumumab clinical trials in LEN-refractory patients (median PFS ~10 months; OS ~27.5 months). 
    • Other real-world studies, such as the UK lenalidomide-refractory cohort and the MAMMOTH study (anti-CD38-refractory disease), also showed short survival and low response rates, reinforcing how difficult this disease stage is to treat.

Strengths and limitations 
    • A major strength is the use of the TM-MM database, which reflects real-world care across Germany. 
    • Limitations include variability in how disease progression and treatment response are assessed in routine practice, missing data from medical charts, and lack of standardized criteria such as IMWG response assessments.

Conclusion 
This study shows that patients with RRMM who have already been treated with LEN and a PI face poor outcomes and limited treatment options. Care is highly variable, reflecting the absence of a clear standard of care. The findings highlight a significant unmet medical need and underscore the importance of developing more effective therapies and treatment strategies for this growing patient population.

Reference: 
K. Martin Kortüm, James Farrell, Olivia Ashman, Guido Nador, Paul Cislo, Jaime Luna, Moritz Lehne, Keltie O’Neill, Markus Rückert, Kai Strobel, Sebastian Theurich, An oBservational retrospective Analysis of treatment patternS and Effectiveness of standard of CAre for Multiple Myeloma patients exposed to lenalidomide and a Proteasome inhibitor: BasecaMMp study, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.01.013.

KarMMa-3 Subgroup Analysis in Older Patients with Relapsed/Refractory Multiple Myeloma Treated with Idecabtagene Vicleucel — Transplantation and Cellular Therapy (February 2026)

Background 
Chimeric antigen receptor (CAR) T-cell therapy is an effective treatment for people with relapsed or refractory multiple myeloma (RRMM). Idecabtagene vicleucel (ide-cel) is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA) and is approved for patients whose myeloma has returned or stopped responding after at least two prior treatments.

What is the purpose of the study? 
This analysis comes from the KarMMa-3 phase 3 clinical trial and compared how well ide-cel works and how safe it is in older (≥70 years) and younger (<70 years) patients with RRMM, compared with standard treatment options.

How was the study conducted? 
KarMMa-3 enrolled adults with RRMM who had received 2–4 prior treatments and whose disease was resistant to their most recent therapy. Patients were randomly assigned to receive either:

    • a one-time infusion of ide-cel, or 
    • one of five standard treatment regimens.

Researchers evaluated treatment outcomes by age, including response rates, progression-free survival (PFS), overall survival (OS), quality of life (QoL), and side effects.

Results 
A total of 386 patients were included. About 20% in each treatment group were aged 70 years or older. Younger patients treated with ide-cel had more high-risk disease features at baseline.

Overall response rate (ORR): 
    • <70 years: 68.8% with ide-cel vs 41.0% with standard therapy 
    • ≥70 years: 81.6% with ide-cel vs 48.1% with standard therapy

Progression-free survival (PFS): 
    • <70 years: 12.5 months with ide-cel vs 4.2 months with standard therapy 
    • ≥70 years: 18.9 months with ide-cel vs 5.7 months with standard therapy

Overall survival (OS): 
    • Not yet reached in older patients in either group 
    • In younger patients: 39.5 months with ide-cel vs 27.9 months with standard therapy

Side effects commonly seen with CAR T-cell therapy, including cytokine release syndrome, neurotoxicity, and infections, occurred at similar rates in older and younger patients treated with ide-cel. Analyses of patient-reported quality of life are ongoing.

Conclusions 
In the KarMMa-3 trial, older patients (≥70 years) experienced strong and lasting benefits from ide-cel, with higher response rates and longer disease control compared with standard treatments. Treatment effectiveness and safety were similar across age groups, supporting the use of a single ide-cel infusion as an effective option for eligible patients with RRMM, including older adults.

Reference: 
Ailawadhi, Sikander et al. KarMMa-3 Subgroup Analysis in Older Patients with Relapsed/Refractory Multiple Myeloma Treated with Idecabtagene Vicleucel. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 32, Issue 2, S34 – S35 February 2026.

Assessing the benefit of incorporating an anti-CD38 monoclonal antibody into second- or third-line systemic treatment for patients with relapsed/refractory multiple myeloma: results from the French real-world EMMY study — Haematologica (February 2026)

Background 
People with myeloma usually receive several lines of treatment over time, with periods of response followed by relapse. Many effective drug classes are now available, including proteasome inhibitors (PI), immunomodulatory drugs (IMiD), anti-CD38 monoclonal antibodies (mAb), bispecific antibodies, and antibody–drug conjugates (ADC). However, the best order/sequencing of these treatments is still not fully defined.

What is the purpose of the study? 
The EMMY study is a large French, real-world, non-interventional study designed to describe how MM treatments are used in routine practice as new drugs become available. This report focuses on patients with relapsed or refractory multiple myeloma (RRMM) who received second- or third-line treatment between 2017 and 2021, comparing outcomes in patients treated with or without an anti-CD38 mAb (daratumumab or isatuximab).

How was the study conducted?

    • 1,784 patients with RRMM were included (median age 72.1 years; ~60% older than 70 years). 
    • 63.2% received second-line and 36.8% third-line treatment. 
    • 822 patients (46.1%) received an anti-CD38 mAb; 962 (53.9%) did not. 
    • Most anti-CD38 mAb–treated patients received daratumumab (88.8%); isatuximab was used in 11.2%. 
    • Baseline characteristics were similar between groups. 
    • Anti-CD38 mAb regimens were increasingly used over time, reflecting drug approvals in France.

Key outcomes measured

    • Time to next treatment (TTNT): time from treatment start to the next treatment or death 
    • Progression-free survival (PFS): time to disease progression or death 
    • Overall survival (OS): time to death

Main results (median follow-up: 21.0 months) 
Patients treated with an anti-CD38 mAb had better outcomes than those without:

    • Median TTNT: 29.8 vs 15.9 months 
    • Median PFS: 26.3 vs 14.5 months 
    • Median OS: not reached vs 46.1 months

Fewer patients treated with an anti-CD38 mAb needed to start another treatment line (33.0% vs 55.8%), and more were still on treatment at the time of analysis.

Context and consistency with other studies

    • About 27% of patients with available data had high-risk cytogenetics. Results are consistent with clinical trials such as ICARIA-MM, which showed the benefits of isatuximab-based combinations regardless of cytogenetic risk. 
    • Findings align with other real-world data, including the Canadian Myeloma Research Group, showing longer PFS and OS with daratumumab-based combinations, especially when used earlier and in combination with drugs like bortezomib, lenalidomide, or pomalidomide.

Limitations 
As a real-world study, results depend on the completeness and accuracy of medical records.

Conclusion 
In routine clinical practice, adding an anti-CD38 monoclonal antibody to second- or third-line treatment for patients with RRMM is associated with longer time to next treatment, longer progression-free survival, and improved overall survival. These results support the important role of anti-CD38 mAb–based regimens in the management of relapsed or refractory multiple myeloma.

Reference: 
Chalopin T, Hulin C, Royer B, Bastie J-N, Bobin A, Merzoug KB, Macro M, Karlin L, Jacquet C, Mohty M, Frenzel L, Sonntag C, Fontan J, Rigaudeau S, Roussel M, Sanhes L, Chaoui D, Vincent L, Orfeuvre H, Bouketouche M, Garlantezec R, Decaux O, Perrot A. Assessing the benefit of incorporating an anti-CD38 monoclonal antibody into second- or third-line systemic treatment for patients with relapsed/refractory multiple myeloma: results from the French real-world EMMY study. Haematologica 2026;111(2):728-732; https://doi.org/10.3324/haematol.2025.287954.  

U.S. Food and Drug Administration (FDA)

FDA accepts new drug application for iberdomide as treatment for relapsed/refractory multiple myeloma

On Tuesday, February 17, the U.S. Food and Drug Administration accepted the new drug application (NDA) for iberdomide combined with standard treatment (daratumumab + dexamethasone) as treatment for relapsed/refractory multiple myeloma (RRMM).

According to a press release from Bristol Myers Squibb, “iberdomide is part of an investigational, new class of medicines called cereblon E3 ligase modulator (CELMoD) agents” and that “the FDA has granted a Prescription Drug User Fee Act (PDUFA) date of August 17, 2026, for this indication.”

The application is based on results from a planned analysis of the Phase 3 EXCALIBER-RRMM clinical trial, which is evaluating iberdomide as treatment for people with RRMM.  

The study compares a three-drug combination of iberdomide + daratumumab + dexamethasone (IberDd) with another three-drug regimen: daratumumab + bortezomib + dexamethasone (DVd).

The trial has two main goals (dual primary endpoints):

    • Minimal residual disease (MRD) negativity, which measures how effectively treatment reduces cancer cells to very low or undetectable levels 
    • Progression-free survival (PFS), or how long patients live without their disease worsening

Additional outcomes being studied include overall survival (OS), overall response rate (ORR), duration of response (DoR), time to progression (TTP), time to next treatment (TTNT), and health-related quality of life (HR-QoL).

The study was conducted in two stages:

    • Stage 1: 1.0 mg was selected as the optimal dose of iberdomide based on safety, drug levels in the body (pharmacokinetics), and efficacy.  
    • Stage 2: approximately 664 patients were randomly assigned to receive either IberDd or DVd.

Based on these results, iberdomide was granted Breakthrough Therapy designation by the FDA — a status intended to speed up the development and review of promising treatments.

The EXCALIBER-RRMM study is still ongoing, and researchers continue to track progression-free survival (PFS).

The review is being conducted through the FDA’s Project Orbis program, which allows health authorities in several countries to review the application at the same time.

References:

U.S. Food and Drug Administration Accepts Bristol Myers Squibb's New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple Myeloma, Bristol Myers Squibb press release, February 17, 2026.

Project Orbis: A framework for concurrent submission and review of oncology products. U.S. Food and Drug Administration, Oncology Center of Excellence.

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.