What are the current treatment recommendations and unmet needs in early RRMM? 

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 in earlier treatment lines 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 (ADCs), for all patients, but particularly those who may not have access to CAR T-cell therapies.

Key learnings

Overview

• In the United States , the use of CAR T-cell therapies in early relapse has been a significant development, with ciltacabtagene autoleucel (cilta-cel) being approved by the U.S. Food and Drug Administration (FDA) after ≥1 prior line of therapy and idecabtagene vicleucel (ide-cel) after ≥2 prior lines of therapy.^1,2
• CAR T-cell therapies have demonstrated unprecedented efficacy in the early relapsed setting, offering durable responses in many patients.^3,4
• Bispecific antibodies, including talquetamab, teclistamab, and elranatamab, are currently approved for patients in later lines of therapy, but are being evaluated for their application in earlier lines, with approvals in this indication expected in time.⁵
• This expanded indication for bispecific antibodies will likely make sequencing of treatment for early relapse more challenging, emphasizing the need for more education.

Unmet need: Identifying functional high-risk patients

• Identifying patients who are at risk for early relapse (disease progression withing 12–18 months of initial treatment) is a significant unmet need. Currently, genetic risk factors, such as 17p deletions and TP53 mutations are often used to predict risk of relapse, but these do not always correlate with early relapse.^6,7
• Immunological factors and immune cell biology may also contribute to early relapse, indicating further research in this area is necessary.
• Preliminary research is also exploring whether magnetic resonance imaging (MRI) patterns could help identify patients likely to experience early relapse.

Unmet need: Optimizing the use of novel therapies

• As novel therapies, including bispecifics, CAR T-cell therapies, and ADCs are approved in additional indications, it is crucial to determine where they best fit in the treatment paradigm.
• CAR T-cell therapies are beneficial for their extended treatment-free intervals and efficacy. However, additional options are needed given the number of patients who are either ineligible for or do not have access to CAR T-cell therapies.
• Belantamab mafodotin has shown promising results as part of combination therapies for patients who relapse after ≥1 prior line of therapy, and may play an important role in the treatment of patients who are not eligible for CAR T-cell therapies or bispecific antibodies.^8,9

Unmet need: Accessing CAR T-cell therapies

• While CAR T-cell therapies offers durable responses and extended treatment-free intervals, there remain significant logistical and clinical barriers globally.
• Some patients with particularly aggressive disease may not be eligible for CAR T-cell therapies due to difficulties in T cell collection or an inability to delay treatment to account for the CAR T-cell manufacturing process.
• Although CAR T-cell therapies have revolutionized treatment for early relapse in certain regions, it remains unavailable to many patients worldwide due to regulatory and logistical limitations.
• Overcoming these barriers are crucial to improving access to effective treatments for patients with MM, globally.

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.