Multiple Myeloma Hub

During the Multiple Myeloma Hub Steering Committee Meeting in April 2025, key opinion leaders met to discuss exportin 1 (XPO1) as a target for the treatment of multiple myeloma (MM) with a focus on real-world evidence. The meeting opened with a presentation by Paul Richardson and featured a discussion including María-Victoria Mateos, Hang Quach, and Morie Gertz. 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.

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. 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. 

In this interview, Hermann Einsele discusses the future perspectives of anti-CD38 antibodies, highlighting their role in first-line treatment for both transplant-eligible and -ineligible patients as well as applications in the second line and smoldering MM. Einsele also discusses outcomes from key trials and outlines potential combinations of anti-CD38s with emerging therapies, including cereblon E3 ligase modulators (CELMoDs), bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies. 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. 

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.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.

The Multiple Myeloma Hub spoke to Sagar Lonial, Winship Cancer Institute of Emory University, Atlanta, US. We asked, What is the rationale for treating early relapsed/refractory multiple myeloma (RRMM) with targeted therapies? 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.

The Multiple Myeloma Hub spoke to Vania Tietsche de Moraes Hungria, Clínica São Germano, São Paolo, BR. We asked, What is the impact of belantamab mafodotin (belamaf) on quality of life (QoL) in patients with multiple myeloma (MM)?  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. 

The Multiple Myeloma Hub spoke with Mohamad Mohty, Hôpital Saint-Antoine and Sorbonne University, Paris, FR. We asked, What is the impact of elranatamab on quality of life (QoL) in relapsed/refractory multiple myeloma (RRMM)? 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 learningsOverall, 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. 

During the European Hematology Association (EHA) 2024 Hybrid Congress, the Lymphoma Hub and Multiple Myeloma Hub held a joint satellite symposium entitled ‘Sequencing immune-based therapies in B-cell malignancies’. 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.

Ciltacabtagene autoleucel (cilta-cel) is a B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell therapy, which is one of only two U.S. Food and Drug Administration (FDA)-approved CAR T-cell therapies for the treatment of relapsed/refractory multiple myeloma (RRMM). Both approved CAR T-cell agents are indicated in the heavily pre-treated setting after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.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