The session covered mechanisms of resistance with BCMA-targeted therapies; the impact of prior exposure to BCMA-directed therapies; the main differences between BCMA-directed antibody–drug conjugates (ADCs), bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies in terms of access, logistics, and toxicity profiles; and how dosing schedules can be adapted to optimize efficacy while limiting toxicity.

This independent educational activity was supported by GSK. All content was developed independently by SES in collaboration with the faculty. The funder was allowed no influence on the content of this activity.

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This independent educational activity was supported by GSK. All content was developed independently by SES in collaboration with the faculty. The funder was allowed no influence on the content of this activity.

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In this presentation, Cook examined how populations enrolled in pivotal trials of BCMA-directed therapies compare with patients treated in routine clinical practice. Key differences were highlighted, including age, performance status, comorbidities, and prior treatment exposure. Cook presented data for bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies, focusing on efficacy and safety outcomes in real-world populations as well as the impact of prior BCMA exposure on response and durability of response. Real-world experience with adverse events, particularly infections and ocular complications, was also discussed, as were the implications of these findings for treatment sequencing as BCMA-directed therapies move into earlier lines of therapy.

This independent educational activity was supported by GSK. All content was developed independently by SES in collaboration with the faculty. The funder was allowed no influence on the content of this activity.

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In this presentation, Bärtsch discussed the rationale for targeting BCMA in MM and reviewed pivotal clinical trial data supporting the approval of BCMA-directed therapies. Bärtsch outlined the mechanisms of action, clinical positioning, and key efficacy and safety findings for antibody–drug conjugates (ADCs), bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies, highlighting differences in availability, toxicity profiles, and durability of response across treatment modalities and lines of therapy.

This independent educational activity was supported by GSK. All content was developed independently by SES in collaboration with the faculty. The funder was allowed no influence on the content of this activity.

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In this interview, Mehmet Hakan Kocoglu discussed the latest updates from the phase I trial of P-BCMA-ALLO1 for RRMM, focusing on the key efficacy and safety data for this allogeneic BCMA-directed CAR T-cell therapy.

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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During his presentation, Lonial provided an overview of approved and investigational CAR T-cell therapies for multiple myeloma, the CAR T-cell therapy treatment process, and multi-step treatment pathway. He explored barriers to treatment with CAR T-cell therapy, racial disparities in access to CAR T-cell therapy, and manufacturing and attrition considerations. He discussed potential strategies for improving access to CAR T-cell therapy for eligible patients, exploring patient selection and referral, optimizing the pre-CAR-T infusion process, use of CAR T-cell therapy in earlier lines of therapy, accelerated manufacturing, and allogeneic CAR T-cell therapies.

This discussion topic is supported by Kite through Gilead Sciences Europe Ltd, who provided funding. All content was developed independently by the steering committee in collaboration with SES. Funders were allowed no influence on the content of the discussion.

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In this interview, Costa first provided an overview of the phase III CARTITUDE-4 (NCT04181827) study design, explaining how the findings have impacted the treatment landscape for multiple myeloma. He then discussed the subgroup of patients in the trial with standard-risk cytogenetics, highlighting the high proportion who remain progression-free 30 months after receiving cilta-cel. He concluded by considering the potential impact of these findings, and the possibility that cilta-cel may offer a single-dose curative option for these patients.

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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During this interview, Popat discussed clinical experience using belantamab mafodotin for patients with relapsed or refractory multiple myeloma (RRMM), highlighting its mechanism as a B-cell maturation antigen (BCMA)-directed antibody–drug conjugate and the practical management of associated ocular toxicities. Popat emphasized key considerations in patient selection, treatment sequencing, and individualized dosing strategies to optimize outcomes while minimizing adverse events. The discussion also covered real-world approaches to monitoring, dose adjustment, and maintaining long-term treatment benefit without compromising safety or efficacy.

This educational resource is independently supported by GSK. 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 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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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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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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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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 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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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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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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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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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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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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In this interview, Professor Quach discussed how the development and integration of BCMA-directed bispecific antibodies have transformed the treatment landscape for relapsed/refractory multiple myeloma (RRMM). Quach covered regulatory approvals, key clinical trial data, strategies for managing toxicities and infections, considerations for community-based treatment, and the adoption of flexible dosing approaches in real-world clinical practice. 

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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During their presentation, Bruno Paiva explored the evolving role of MRD in MM, highlighting both clinical and research applications. Paiva reviewed current MRD detection methods, evaluated sustained MRD negativity as an indicator for long-term survival outcomes, discussed the value of MRD as an early endpoint in clinical trials, and outlined scenarios where MRD could guide treatment decisions, such as fixed-duration therapy or reinitiation upon MRD resurgence. 

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In the presentation, Dr Richardson discussed the role of XPO1 as a target for the treatment of relapsed/refractory MM. Richardson discussed the mechanism of action for XPO1 inhibitors, as well as the clinical trial data, and real-world experience associated with selinexor, a first-in-class selective inhibitor of nuclear export, in heavily pretreated patient populations. During the discussion, the steering committee members provided insight into combination regimens, strategies to manage toxicities, and the potential positioning of selinexor in current treatment algorithms for MM.

This educational resource is independently supported by Karyopharm. 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 Rakesh Popat, University College Hospital, London, UK. We asked, How to incorporate novel therapies into the treatment paradigm for early relapsed/refractory multiple myeloma (RRMM)? 

In this interview, Dr Popat discussed the evolving treatment landscape for early RRMM, highlighting the integration of novel agents, particularly B-cell maturation antigen (BCMA)-directed therapies including belantamab mafodotin. The discussion outlined both the efficacy and toxicities associated with belantamab mafodotin combination regimens, emphasizing the importance of adapted dosing schedules. Popat also discussed strategies for sequencing BCMA-directed therapies, including chimeric antigen receptor T-cell therapy and bispecific antibodies. 

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This educational resource is independently supported by Sanofi. 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 was pleased to speak with Rahul Banerjee, Fred Hutchinson Cancer Research Center, Seattle, US. We asked about the current treatment recommendations and unmet needs in early relapsed/refractory multiple myeloma (RRMM).

In this interview, Banerjee evaluates the latest advancements and unmet needs in the treatment of early RRMM, highlighting the approval of chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies for early relapse as major developments. Banerjee also discusses the challenges of identifying patients at risk for early relapse and assesses the potential for emerging therapies, such as antibody–drug conjugates, for all patients, but particularly those who may not have access to CAR T-cell therapies.

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In this interview, Lonial discusses how the treatment landscape for early RRMM has changed over time, impacting the effectiveness of standard of care therapies and leading to an increased interest in new targeted approaches, such as CAR T-cell therapies, bispecific antibodies, and antibody–drug conjugates. Lonial outlines the latest regulatory updates and available options for patients who are ineligible for or unable to access all advanced therapies.

This educational resource is independently supported by GSK. 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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Hungria provided insights into the mechanism of action of belamaf, its efficacy and safety in heavily pre-treated patients, and the latest findings from the phase III DREAMM-7 (NCT04246047) study. Hungria discussed how belamaf in combination with bortezomib and dexamethasone (BelaVd) impacts disease progression, survival, and patient-reported outcomes compared to daratumumab with Vd (DaraVd). This discussion also evaluated the safety profile of belamaf, including ocular side effects and their impact on QoL. 

Key learnings 

• Belamaf is an antibody–drug conjugate that targets the B-cell maturation antigen on malignant plasma cells. 
• Belamaf has previously demonstrated promising anti-myeloma activity and a manageable safety profile as a sole agent in patients with heavily pre-treated MM. 

DREAMM-71,2 

• DREAMM-7 is a phase III, randomized study evaluating BelaVd vs DaraVd in patients with relapsed/refractory MM. 
• A statistically significant benefit in progression-free survival, overall survival, duration of response, and measurable residual disease negativity were observed with BelaVd. 
• Patients reported stable quality of life, physical functioning, fatigue, and disease symptoms, with no significant differences between treatment arms. 
• Ocular toxicities were more common during the initial phase of treatment but generally improved as dosing frequency was reduced, highlighting dose modification as an effective strategy to manage these effects. 
• Among patients who experienced a clinically meaningful decline in visual acuity, overall QoL remained comparable to those treated with DaraVd. 
• BelaVd has a limited impact on health-related QoL, supporting its potential as a new standard of care treatment for relapsed/refractory MM. 

This educational resource is independently supported by GSK. All content was developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource. 

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Mohty discussed the impact of elranatamab on QoL in patients with RRMM, highlighting its benefits in symptom relief, mobility, and overall well-being. Mohty also addressed the associated risk of cytokine release syndrome (CRS), neurotoxicity, and infections, concluding with the latest clinical trial data and emphasizing the need for ongoing research to optimize the role of elranatamab and other bispecific antibodies in patient care.  

Key learnings

• Overall, elranatamab has positively impacted QoL in many patients with RRMM by providing rapid symptom relief, reducing bone pain and fatigue, improving mobility, and decreasing healthcare visits. 
• Better disease control also contributes to improved psychological well-being. 
• These benefits ultimately enhance daily functioning and overall well-being, allowing patients to resume their daily activities. 
• Adverse events are a concern; however, the implementation of step-up dosing helps to reduce the risks of severe CRS and neurotoxicities. 
• The risk of infections remains significant. However, mitigation strategies such as prophylactic antivirals, antifungals, and intravenous immunoglobulin administration can help preserve QoL. 
• Clinical trial data from the MagnetisMM-3 (NCT04649359) trial support these findings, demonstrating improved patient-reported outcomes in global health status, functional ability, and symptom management. 
• Ongoing trials aim to further clarify the role of elranatamab and other bispecific antibodies in enhancing QoL. 

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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Here the Multiple Myeloma Hub is pleased to share the session: Next wave of immune-based therapies: What you need to know, which focused on relapsed/refractory (R/R) multiple myeloma (MM) and was presented by Krina Patel, MD Anderson Cancer Center, Houston, US.

This activity was supported through an educational grant from Bristol Myers Squibb.

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However, in February 2024, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of cilta-cel after at least one prior line of therapy, including an immunomodulatory agent or proteasome inhibitor, for those who have progressed on the last therapy and are refractory to lenalidomide.

The Multiple Myeloma Hub is pleased to summarize the rationale for and latest data from clinical trials of cilta-cel after one to three lines of therapy for the treatment of MM.

Read the article here: https://multiplemyelomahub.com/medical-information/integrating-cilta-cel-into-earlier-lines-of-therapy-rationale-and-latest-data-from-cartitude-2-and-cartitude-4

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To read this article on the Multiple Myeloma Hub, click here: https://multiplemyelomahub.com/medical-information/teclistamab-real-world-safety-and-efficacy

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

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Following her presentation, Beksaç​ chaired a Q&A session featuring Hermann Einsele, Paul Richardson, Heinz Ludwig, María-Victoria Mateos, Elena Zamagni, and Vania Tietsche De Moraes Hungria. Discussions included COVID infections, the need for vaccination in donors of immunoglobulins for IVIG treatment, and the impact of dosing schedules on reducing infectious complications and T‑cell exhaustion. 

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To open, Hermann Einsele provides a presentation reviewing the latest data from trials of ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) in relapsed/refractory multiple myeloma (RRMM), including the KarMMa and CARTITUDE trials. He explores criteria for the identification of patients who may benefit from CAR T-cell therapy, mechanisms of resistance to BCMA CAR T-cell therapy, and the rationale for the earlier application of CAR T-cell therapies in MM. Einsele provides a review of the toxicities associated with immunotherapies, including strategies for prevention and monitoring, management techniques for CRS and ICANS, and infection prophylaxis and management. 

Following his presentation, Einsele chaired a Q&A session featuring Paul Richardson, Heinz Ludwig, María-Victoria Mateos, Meral Beksaç, Elena Zamagni, and Vania Tietsche De Moraes Hungria. 

Discussions included the implementation of CAR T-cell therapies in earlier lines of therapy, CAR T-cell therapies in high-risk disease, maintenance after CAR T-cell therapies, and toxicities with CAR T-cell therapies and bispecifics. 

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

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In this expert discussion, Shaji Kumar and Naresh Bumma provide their insights into post-ASCT maintenance therapy for high-risk patients. The experts consider the use of lenalidomide as a monotherapy versus in combination with a proteosome inhibitor, whilst sharing their thoughts on the challenges in defining the high-risk population.

Kumar and Bumma present their individual management strategies for this patient population and examine existing clinical data, highlighting the need for prospective trials. This discussion concludes with a look to the future management of high-risk multiple myeloma post-ASCT.

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In this podcast, Hira Mian discusses the relationship between age and frailty status, sharing her perspective on how they may inform treatment strategies for patients with multiple myeloma. Mian examines the influence of age on frailty status, but notes other influential factors featured in the International Myeloma Working Group (IMWG) frailty score. Mian concludes with the importance of a comprehensive frailty assessment to inform a risk-adapted treatment plan.

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In this interview, Schmidt discusses their poster presented at ASH 2022 entitled: Humoral immune reconstitution following therapy with daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd), autologous hematopoietic cell transplantation (AHCT) and MRD-response-adapted treatment cessation. Schmidt discusses this post hoc analysis of the MASTER trial, examining the markers for humoral immune reconstitution amongst patients who were able to cease therapy, based on two successive MRD-negative assessments. Moving forward, Schmidt goes on to outline the results of humoral immune reconstitution based on whether patients ceased therapy following transplant or after transplant and Dara-KRd consolidation. Schmidt concludes by considering the potential of replicating this method of analysis in other studies.

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In this podcast, Hungria discusses their poster presented at ASH 2022 entitled: A Brazilian real-life experience of multiple myeloma patients: Final results from the Mmybrave multi-center study.

In particular, Hungria discusses the setting of this research, looking at the differences in the characteristics and overall survival of patients with MM in Brazil, considering the treatment center type, i.e., public or private institutions. Hungria considers the difference in access to drugs and the implications this may have on patients, and concludes by looking to the future for the improvement of treatment for all patients with MM in Brazil.

To find out more about this research study, read the Multiple Myeloma Hub summary here.

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In this podcast, Beksac discusses their poster presented at ASH 2022 entitled: Efficacy of daratumumab combined with bortezomib, cyclophosphamide and dexamethasone for the treatment of multiple myeloma patients presenting with extramedullary disease: a European Myeloma Network study. Beksac outlines the methods and motivations for this phase II open-label study, including the unmet need for patients with para-skeletal plasmacytomas, and concludes by discussing the study results in terms of progression-free survival, safety, and efficacy, and comparing these results with the previous LYRA study.

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Hájek begins by explaining that isatuximab is an anti-CD38 monoclonal antibody currently approved for treatment in combination with pomalidomide + dexamethasone or carfilzomib + dexamethasone. This is followed by a discussion on why these combinations may be helpful for patients previously exposed or refractory to lenalidomide.

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Mateos begins the discussion by posing the question of how to integrate chimeric antigen receptor (CAR) T-cell and other BCMA-directed products into clinical practice. Shah discusses the problems of CAR T-cell product availability, as well as the potential of bispecific therapies as they are more readily available. Richardson talks about antibody—drug conjugates (ADCs) and combination therapies, and the risk of keratopathy with some treatments. The committee discuss the convenience of ADCs and the potential of combinations using bispecific therapies and ADCs, with Gertz mentioning the exclusion of some patient subgroups from CAR T-cell trials, meaning bispecifics may be the best alternative for these individuals. Finally, Ludwig talks about the importance of more data becoming available to evaluate the use of BCMA-directed agents in earlier lines of therapy.

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Gertz begins the discussion by explaining that patients often have confusion over what consolidation therapy is and when it can be used. Mateos then discusses how the number of induction therapy cycles a patient receives can affect the use of consolidation. Richardson talks about the STAMINA trial and how tolerability posttransplant can affect treatment choices, with Shah commenting on the difficulty of replicating trials in the real-world setting. The committee then discuss how historically in trials, the same drug that was used in induction is used as consolidation, and what the potential results would be if a different drug was used for consolidation.

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Mina and Jakubowiak discuss the MajesTEC-1 and MagnetisMM-1 trials, the efficacy and response rates of bispecific antibodies, and the challenges of using bispecific antibodies, such as infection risk. They also compare bispecific antibodies to CAR T-cell therapies and talk about the sequencing of therapies in myeloma treatment.

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Mateos begins by giving an overview of the bispecific antibodies, talquetamab and teclistamab. These antibodies have been investigated in combination with daratumumab in two clinical trials; Mateos provides a summary of the results of these trials, including the safety and efficacy data.

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In this podcast, Laubach and Voorhees discuss the findings from the randomized phase II GRIFFIN trial (NCT02874742) and the CASSIOPEIA trial (NCT02541383). 

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Raje and Delforge discuss the management of infections with novel immunotherapies, including: monoclonal antibodies, antivirals, risk of infection, intravenous immunoglobulin, and the impact of COVID-19. This podcast closely links to our latest editorial theme, in which the Multiple Myeloma Hub explores how to manage adverse events from novel agents, with our first article examining proteasome inhibitors and cardiovascular events.

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This podcast captures the roundtable discussion with Mohamad Mohty, Hôpital Saint-Antoine and Sorbonne University (Paris, FR), María-Victoria Mateos, University Hospital of Salamanca (Salamanca, ES), and Sagar Lonial, Winship Cancer Institute of Emory University (Atlanta, US), and includes the concluding remarks of the Satellite Symposium as a whole.

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In this podcast, Rajkumar discusses the current standard of treatment for elderly, frail patients (VRd−bortezomib, lenalidomide, dexamethasone) and regimens that are currently being tested across various clinical trials to improve upon this standard, such as replacement of bortezomib with carfilzomib or daratumumab, and quadruplet combinations. He then discusses if a cure is really feasible for MM, and highlights some key considerations for a true cure; when treatment is given for a finite time and the disease never returns. He concludes with his recommendations for assessing MM cure in future trials.

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In this podcast, Lonial describes results from the FORTE (NCT02203643) and IFM 2009 (NCT01191060) trials, which investigated the use of triplet combinations with and without transplant. He warns of the 'siren song' of early MRD negativity that may lead one to believe novel agents are just as good as transplant. Lonial highlights that the focus needs to be on sustained MRD negativity; rates of which were higher in the patients who received a transplant. He also highlights two reasons for the discrepancy seen among early MRD negativity and sustained MRD negativity between patients who received a transplant and those who did not.

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The podcast focuses on both hematologic and organ response in amyloidosis, as well discussing the findings of a recent study.

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In this podcast, Mateos discusses the progression of monoclonal gammopathy of undetermined significance (MGUS) and SMM to MM from a molecular point of view. She explains the 2/20/20 risk stratification model for SMM, and the phase III clinical trials that have demonstrated a benefit in treating patients with high-risk SMM to delay the progression to overt MM. In her road map to cure MM, early treatment of SMM is a crucial step, and she presents two curative approaches being currently investigated in clinical trials.

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In this podcast, Mohty discusses how the word 'cure' has different implications for young and older patients, and discusses the functional/operational cure for patients with standard- and high-risk disease. Mohty focuses on the importance of sustained MRD negativity on survival and why it should also be monitored by PET-CT. Seeing novel agent combinations reaching unprecedented results, he is hopeful that the cure rates will rise in both young and older patients with MM in the near future.

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In this podcast, Mo and Nadeem discuss factors to be considered with regimen options for patients with lenalidomide-refractory MM. They discuss cardiac risk factors, lines of therapy, prognosis, and end the podcast on the topic of new agents.

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In this podcast, Sonneveld discusses trial results presented during EHA2021 on the efficacy of novel treatments for patients with high-risk MM, a patient group associated with poor outcomes and shorter remission rates. He believes that identifying high-risk patients and selecting them for more intensive targeted maintenance treatment could be crucial in preventing relapse.

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Leleu discusses three alternatives to anti-B-cell maturation antigen (BCMA) directed therapies, including alternative drugs (provided the patient is nonrefractory), enrolment to clinical trials investigating new treatments, and the use of developing agents administered in the context of compassionate use.

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In this podcast, McCarthy discusses the two main chimeric antigen receptor (CAR) T-cell toxicities: cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Initially, McCarthy lists what to look out for in terms of symptoms in this highly practical podcast episode. He then describes the timeline for the appearance of these adverse advents and the current treatment strategies that are being used.

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Callander and Kumar discuss the inclusion of new diagnostic tools, such as MRD testing, risk-stratification for MM and it’s precursor stages, and changes to treatment regimens for newly diagnosed and relapsed MM. Callander also describes an important update for the recommendation of the combination of daratumumab, cyclophosphamide, bortezomib, and dexamethasone for the treatment of amyloidosis, providing supporting data from the phase III ANDROMEDA trial. They finish by discussing risk stratification and treatment intervention updates for smoldering MM.

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Currently, the only approved maintenance therapy for multiple myeloma is lenalidomide. When answering whether this treatment is worth it, Jackson provides meta-analysis results of the CALGB 100104, IFM 2009, and Myeloma XI studies demonstrating improved progression-free survival by around 20−30 months compared with placebo.

Jackson and Moreau then discuss alternative treatments in patients who are refractory to lenalidomide, focusing on optimizing carfilzomib + dexamethasone, daratumumab, bortezomib + dexamethasone, and pomalidomide + dexamethasone-based regimens.

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In this podcast, Manasanch and Kourelis describe two studies on immune microenvironment changes in myeloma. The first study is a preliminary analysis of peripheral blood and bone marrow samples from patients with smoldering myeloma. This included identifying changes to immune cell composition and using RNA/DNA sequencing to identify biomarkers associated with immune changes in patients with disease progression. From the data, they outline possible new avenues in immune cell profiling for the prognosis of high-risk precursor patients, as well as therapeutic targeting, including the potential for curing at the precursor stage.

The second study for discussion compared major components of tumor ecosystems in patients with newly diagnosed/relapsed myeloma that are triple-class refractory. Kourelis brings attention to unhealthy T-cell compartments in more heavily pretreated patients compared with patients with newly diagnosed/relapsed disease and the implications for their response to T-cell-based immunotherapies.

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In this podcast, Kaufman and Gay discuss data from studies evaluating multiple myeloma treatment with proteasome inhibitors (bortezomib or carfilzomib) + lenalidomide. Both highlight improved progression-free survival with combination therapy vs monotherapy, particularly in high-risk patients. They also discuss difficulties related to patient compliance with combination therapy and issues related to continuous hospital visits resulting from the method of administration and therefore suggest potential oral alternatives to improve compliance.

Kaufman then moves on to data from the phase II GRIFFIN trial, evaluating the addition of daratumumab (DARA) to lenalidomide, bortezomib, and dexamethasone induction and consolidation, followed by maintenance therapy with lenalidomide or DARA + lenalidomide. Gay also mentions the MAIA study evaluating DARA + lenalidomide and dexamethasone in transplant-ineligible patients. Kaufman concludes by highlighting the importance of evaluating methods to shorten post-transplant maintenance time without losing any long-term benefits.

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In this podcast, Munshi discusses the role of high-dose chemotherapy combined with stem cell transplantation in the era of novel agents. Upon analyzing data from a genomic-focused study, he concludes that high-dose melphalan can still achieve good and deep responses, while maintenance therapy should also be an important treatment component for multiple myeloma.

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AL amyloidosis is a rare disease caused by the accumulation of amyloid fibers in tissues and organs. In this podcast, Kastritis outlines the need for a more accurate and earlier diagnosis of AL amyloidosis. Kastritis then discusses the need for new therapeutic strategies in patients with advanced (stage IIIb) AL amyloidosis. Finally, he mentions the need for optimized treatment in patients who relapse.

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Long-term follow-up data about upfront autologous hematopoietic stem cell transplantation (auto-HSCT) were presented at the 62nd ASH Annual Meeting and Exposition. Mohty and Braunstein agree on the importance of auto-HSCT and on the fact that, when possible, it should not be delayed.

They outline the value of upfront auto-HSCT even in the era of novel agents being developed for multiple myeloma. They also talk about consolidation and maintenance therapy after transplant.

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Merz highlights the importance of defining what you want to study, the myeloma cells or the tumor microenvironment. He explains that with single cell sequencing it is possible to analyze different clones that are present in every patient with myeloma, and that in the future it will be important to look at risk-stratified therapy and identify modes of resistance. He also states that with single cell sequencing we can understand why certain therapies work in certain patients.

Bahlis focuses on non-plasma cell compartment and single cell techniques. He gives an overview of the studies on single cell sequencing presented at ASH 2020. He also reports the results of a study performing a broad immunophenotypic and transcriptomic characterization, at the single cell level, of the peripheral blood and bone marrow T cells of sensitive and resistant patients with multiple myeloma treated with B-cell maturation antigen-targeted chimeric antigen receptor T-cell and bispecific T-cell engager therapies.

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Bispecific antibodies and chimeric antigen receptor (CAR) T cells represent a novel interesting therapeutic option for patients with multiple myeloma. In this podcast, after explaining their mechanism of action, Hermann Einsele gives an overview of the major findings from clinical trials evaluating efficacy and safety of bispecific antibodies and CAR T cells.

The advantage of bispecific antibodies in comparison to CAR T cells is that they are probably less toxic, with less severe cytokine release syndrome and lower neurotoxicity, thus more suitable for patients who are less fit. However, CAR T cells seem to be more effective, with response rates of up to 100% and complete remission rates that can be above 80%.

In summary, both bispecific antibodies and CAR T cells are new immunotherapeutic strategies that show promising results in patients with multiple myeloma.

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In this podcast, Dr Davar starts by providing a background on the importance of the microbiome in adaptive and innate immunity, while Dr Spencer states the importance of the cross-talk between the microbiome and immune system through microbial products, peptides, and metabolites. Dr Davar then explains the concept of immunosurveillance, immunoediting, and checkpoint inhibitors. Dr Spencer describes fecal microbiome transplant studies that showed features of the microbiome can predict response to immunotherapy and effect T-cell expression. Dr Davar then describes some of the studies that are looking at fecal microbiome transplant in combination with checkpoint inhibitors. He goes on to discuss studies investigating the use of live bacterial products to elicit the same effects as fecal microbiome transplant, particularly the mediation of CD8 T cells. Dr Spencer also talks about probiotics, antibiotics, and diet and explains how this can affect the gut microbiome and describes studies looking at these features in terms of response to immunotherapies. She also describes the microbiome research related to graft-versus-host-disease and the impact of higher alpha diversity on post-transplant survival, while Dr Davar explains how the microbiome may also affect toxicity and side-effects of cancer immunotherapies. 

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Melflufen has been successful in overcoming resistance to standard chemotherapeutics as well as novel agents, such as proteasome inhibitors and immunomodulatory drugs. The high lipophilicity of melflufen facilitates rapid entry into myeloma cells. Furthermore, its alkylating activity is initiated by aminopeptidases, which are often overexpressed by myeloma cells, making the agent particularly selective. As a result, melflufen is better tolerated, with fewer off-target effects than its predecessor, melphalan.

Here, Paul Richardson discusses the major findings from preclinical studies and topline data from ongoing clinical trials evaluating melflufen for the treatment of multiple myeloma.

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In this podcast, Katja Weisel describes the interim results of the phase II GMMG-CONCEPT trial including deep and durable responses, measurable residual disease negativity, remissions, and overall survival of the first 50 patients enrolled. She also discusses the trial design, including the cytogenetic features that classify patients as high risk, as well as the safety profile and dosing regimens.

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Paul Richardson describes how preclinical data have shown CC-92480 to have potent and direct anti-myeloma and immunostimulatory effects. He discusses the results from the phase I, multicenter, international study that combined CC-92480 with dexamethasone in patients with relapsed and refractory multiple myeloma and describes the two dosing regimens (continuous and intensive), patient characteristics, and safety data. Dr Richardson also explains that the results show encouraging, durable responses, particularly for patients that have triple-refractory myeloma, which are a sub-group of patients where there is a significant clinical unmet need.

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He describes the progression free survival, overall survival and safety profile of the 100 patients that were evaluable from the SWOG 1211 trial. This was a randomized, phase II trial, which evaluated lenalidomide, bortezomib and dexamethasone (RVd) induction followed by dose-attenuated RVd maintenance until disease progression with or without elotuzumab, in patients with high risk, newly diagnosed multiple myeloma.

He then talks about the dose escalation results of first-in-human trial of teclistamab, a BCMA bispecific antibody, in terms of overall response rates and safety profile. He then mentions the randomized phase III study looking at belantamab mafodotin in combination with RVd in patients with transplant ineligible newly diagnosed multiple myeloma.

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Here, Nikhil Munshi highlights the positive shift in survival outcomes of patients with high-risk MM in recent years, owing to emerging treatments and diagnostic techniques. Three major points are discussed:

1. Who is high risk?

2. What are the characteristics of high-risk MM?

3. How do we treat patients with high-risk disease?

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Oral microbiome characteristics are highly heterogeneous between patients, and a higher microbiome diversity has been associated with favorable prognosis in patients with cancer. However, there remains a lack of data surrounding the influence of the oral microbiome on survival outcomes in patients with MM. This study sought to provide answers—listen for more information!

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Adam Cohen provides us with insights from pre-clinical data and explains the mechanism of action of BFCR4350A. He also describes the expression patterns of its target FcRH5, which make this drug less likely to have off-target effects and be specifically efficacious in patients with an amplification at the 1q21 locus. He also discusses the study design, criteria, and objectives of the phase I trial, including a step-up dosing regimen aimed to mitigate cytokine syndrome and neurotoxicity.

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Nikhil Munshi describes the mechanism of action of the idecabtagene vicleucel (ide-cel) BCMA targeting CAR T-cell therapy before detailing the study design. He then provides results from the 128 patients enrolled in the study, including and dose-response rates, overall response rates, complete response rates, and MRD negativity rates. He also describes the safety profile including cytokine release syndrome, neurotoxicity and cytopenias. These results demonstrate deep and durable responses for a heavily pre-treated patient population with relapsed/refractory multiple myeloma.

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Jesus Berdeja begins by explaining the construct is different to other BCMA CAR T-cell constructs and then goes on to describe the study design, including patient characteristics and eligibility. He then describes the safety results from this study including the late onset of cytotoxic syndrome. He also discusses the overall response rate and measurable residual disease negativity.

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She begins be describing the uniqueness of TAK-079 over other approved anti-CD38 antibodies and describes the mechanism of action. Amrita Krishnan then begins to discuss the promising safety and tolerability results including no infusion-related reactions and no significant lymphopenia or thrombocytopenia.

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Shaji Kumar discusses the results of the primary endpoints: progression-free survival, and duration of therapy, as well as the secondary endpoints: MRD-negativity, overall survival, and toxicity. He also discusses quality of life metrics, including renal and neurotoxicity-related symptoms. As this study excluded high-risk patients, Shaji Kumar briefly describes the results of another trial (S1221) that enrolled a high-risk patient population to fully answer the question.

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In this podcast, Elizabeth O'Donnell discusses how bone-directed therapy is an important component of multiple myeloma (MM) therapy. She describes the study which led to the FDA approval of denosumab, before describing results from the ongoing phase II, single-arm study of denosumab in patients with MM with real insufficiency (creatinine clearance < 30). She focuses on the safety profile and adverse events including neurotoxicities and hypocalcemia.

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The question remains for patients with smoldering MM: when should therapeutic intervention begin? Here, Irene Ghobrial discusses the need for more robust disease-characterizing and patient-defining criteria.

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Enrique M. Ocio begins by describing how first-line treatments for this population of patients have changed recently, and then provides results from a study investigating the use of isatuximab (an anti-CD8 monoclonal antibody) in combination with quadruplet regimens; bortezomib + cyclophosphamide + dexamethasone (VCd) or bortezomib + lenalidomide + dexamethasone (VRd). He provides efficacy, safety and tolerably data as well as measurable residual disease analysis, and concludes with his perspective on which treatments should be used for elderly patients.

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A number of factors may influence a patient's eligibility for, and outcome to, different treatments in the MM setting. Here, Paula Rodriguez Otero discusses these factors and outlines the available treatment options for patients deemed ineligible for transplant.

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Although advances in treatment options for MM have improved the outcome of patients in recent years, resistance remains a problem and MM is still considered an incurable disease. Here, Enrique Ocio discusses the importance of understanding the mechanisms behind both primary and secondary resistance in order to overcome them.

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In this podcast, Artur Jurczyszyn talks about the classifications of plasma cell leukemia and the importance of outlining a plasma cell prognostic index for use in clinical practice. The data from two retrospective analyses, evaluating primary and secondary plasma cell leukemia, are discussed.

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