Multiple Myeloma Hub

The Multiple Myeloma Hub spoke with Paul Richardson, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, Massachusetts, US. We asked about the clinical implications of findings from the phase III MIDAS trial (NCT04934475), which evaluated a measurable residual disease (MRD)-driven consolidation and maintenance strategy after induction with isatuximab + carfilzomib + lenalidomide + dexamethasone (Isa-KRd) in patients aged less than 66 years with newly diagnosed (ND), autologous stem-cell transplantation (ASCT)-eligible multiple myeloma (MM) (N = 791).

The primary end point of the MIDAS trial was measurable residual disease (MRD)-negative status at 10−6 sensitivity before maintenance therapy. An additional aim was to evaluate the benefit of high-dose melphalan with ASCT (the current standard care) compared with Isa-KRd alone in patients who were MRD-negative at 10−5 sensitivity post induction.

During this interview, Richardson discussed findings from the MIDAS trial, published by Perrot el al. in Blood and NEJM, and presented at the 2025 American Society of Clinical Oncology Annual Meeting.

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The Multiple Myeloma Hub spoke with Paul Richardson, Dana-Farber Cancer Institute, Boston, US. We asked, How might the clinical development of cereblon E3 ligase modulators (CELMoDs) impact the treatment paradigm for multiple myeloma (MM)?

During this interview, Paul Richardson discussed the emerging role of CELMoDs in MM. Richardson reviewed the rationale for the development of these agents, what distinguishes them from traditional immunomodulatory agents (IMiDs), and the unmet needs they were designed to address in relapsed and refractory disease (RRMM). Richardson summarized clinical trial results with iberdomide and mezigdomide, highlighted their applications in high-risk and heavily pretreated patients, and emphasized their potential for use in earlier treatment settings and as maintenance therapy. Richardson also outlined ongoing phase III studies and novel combination strategies designed to optimize patient outcomes.

This educational resource is independently supported by Bristol Myers Squibb. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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The Multiple Myeloma Hub spoke with María-Victoria Mateos, University Hospital of Salamanca, ES. We asked about the latest findings from the updated follow-up of CARTITUDE-2 Cohort D.

During this interview, Mateos discussed the latest outcomes from the phase II CARTITUDE-2, multicohort study evaluating ciltacabtagene autoleucel (Cilta-cel) across various clinical settings of unmet need. She covered the updated follow-up data (40.2 months) from Cohort D from the trial, as presented at the 22nd IMS Annual Meeting (September, 17–20, 2025), investigating Cilta-cel + lenalidomide (Len) maintenance in patients with newly diagnosed multiple myeloma (NDMM) who achieved less than a complete response after autologous stem cell transplantation (ASCT) as first-line therapy (N = 17). Mateos highlighted the deep and durable responses to treatment, including achievement of measurable residual disease (MRD) negativity, and noted that no new safety signals were reported with the longer follow-up. She concluded that the benefit–risk ratio of Cilta-cel continues to be favorable for this patient population.

This educational resource is independently supported by Legend Biotech. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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The Multiple Myeloma Hub spoke with María-Victoria Mateos, University Hospital of Salamanca, Salamanca, Spain. We asked about the evolving diagnostic criteria for high-risk smoldering MM.

During this interview, Mateos discussed the latest updates in the diagnosis, prognosis, and management of high-risk smoldering MM. The discussion covered the diagnostic criteria that distinguish smoldering MM from monoclonal gammopathy of undetermined significance and active MM, with emphasis on the role of myeloma-defining events. Mateos outlined updates to risk stratification models, including the International Myeloma Working Group 2/20/20 model and its integration with cytogenetics, along with alternative approaches such as flow cytometry, positive emission tomography imaging, genomic profiling, and dynamic models like PANGEA. Mateos highlighted the importance of identifying patients with high-risk smoldering MM, given the significantly higher risk of progression among these patients, and reviewed data from clinical trials supporting therapeutic intervention in this setting. Mateos concluded with an overview of more novel approaches under investigation, including CAR T-cell therapies and bispecific antibodies.

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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The Multiple Myeloma Hub spoke with Ravi Vij, Washington University, St. Louis, US. We asked, What combination regimens including bispecific T-cell engagers (BiTEs) are being evaluated for the treatment of relapsed/refractory multiple myeloma (RRMM)? 

 During this interview, Ravi Vij discussed combination strategies involving BiTEs for the treatment of RRMM. Vij highlighted the movement of B-cell maturation antigen (BCMA)- and G-protein-coupled receptor family C group 5 member D (GPRC5D)-directed BiTEs into earlier lines of therapy and their integration into regimens with established agents such as daratumumab, pomalidomide, and lenalidomide. In addition, Vij noted that novel FcRH5-directed BiTEs such as cevostamab are being investigated in combination regimens, with early-phase studies reporting high response rates, including complete responses. Vij concluded that while results are encouraging, concerns remain regarding increased risk of infections and the need for more mature data on durability of response and progression-free survival prior to regulatory approvals of new agents or combinations.

This educational resource is independently supported by Roche. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource. 

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The Multiple Myeloma Hub spoke to Irene Ghobrial, Dana-Farber Cancer Institute, Boston, US. We asked about risk stratification and prognosis in smoldering multiple myeloma (MM).

During this interview, Ghobrial discussed risk stratification and prognosis in smoldering MM, with a focus on whether high-risk smoldering MM should be treated early. Ghobrial emphasized the heterogeneity of the condition, which ranges from indolent disease to high-risk cases with an approximately 50% likelihood of progression within 2 years. High-risk smoldering MM is a true malignancy, with plasma cells actively proliferating despite the absence of symptoms or myeloma-defining events. Early treatment was highlighted as a potential opportunity to achieve long-term disease control, with supporting data from the AQUILA study and other clinical trials indicating that therapies such as daratumumab can improve progression-free and overall survival for these patients. Ghobrial concluded by noting that advances in immunotherapy, including bispecific antibodies and CAR T-cell therapy, may enable earlier, fixed-duration treatment strategies that prevent end-organ damage and potentially achieve cure in high-risk smoldering MM.

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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The Multiple Myeloma Hub spoke with Alexander Lesokhin, Memorial Sloan Kettering Cancer Center, New York, US. We asked, What combination regimens containing B-cell maturation antigen (BCMA)-directed bispecific antibodies are being evaluated for multiple myeloma (MM)?

In this interview, Lesokhin discussed the range of combination regimens featuring a BCMA-directed bispecific antibody for MM, outlining the rationale for these strategies and noting that while BCMA bispecifics have shown high response rates in the relapsed/refractory setting outcomes can be further improved. Lesokhin reviewed combinations with other bispecific antibodies, established MM therapies, and other novel agents including checkpoint inhibitors and those that can enhance BCMA expression on malignant cells.

This educational resource is independently supported by Pfizer. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

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The Multiple Myeloma Hub spoke with Peter Forsberg, Colorado Blood Cancer Institute, Denver, US. We asked, How can neurotoxicity associated with chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM) be managed? 

In this interview, Dr Forsberg explored the evolving understanding and management of neurotoxicity associated with CAR T-cell therapy in MM. Forsberg highlighted current strategies for managing these toxicities and identifying patients at higher risk, concluding by emphasizing the importance of collaboration among healthcare professionals to refine diagnostic criteria and optimize therapeutic interventions as CAR T-cell therapy becomes increasingly integrated into the MM treatment paradigm. 

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource. 

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The Multiple Myeloma Hub spoke with Sagar Lonial, Winship Cancer Institute of Emory University, Atlanta, US. We asked, What might be the future applications for B-cell maturation antigen (BCMA)-directed bispecific antibodies in multiple myeloma (MM) and other plasma cell dyscrasias?

In this interview, Sagar Lonial discussed the expanding role of BCMA-directed bispecific antibody therapies beyond relapsed/refractory MM, including their potential applications in high-risk smoldering MM and light-chain (AL) amyloidosis. Lonial also evaluated emerging strategies for optimizing dosing schedules, enhancing the patient experience, and mitigating treatment resistance.

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource. 

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The Multiple Myeloma Hub spoke with Shaji Kumar, Mayo Clinic, Rochester, US. We asked about the future perspectives for the treatment of patients with high-risk smoldering multiple myeloma (MM). 

In this interview, Dr Kumar explored the emerging treatment landscape for high-risk smoldering MM, highlighting a shift from active monitoring to intervention. Kumar discussed the increasing evidence supporting early treatment in patients at high risk of progression to active MM, including data from clinical trials.  

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource. 

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