EHA 2025 | Treatment strategies for patients with R/R amyloidosis: targeting BCL2 or BCMA

Patients are now uniformly treated, almost all patients with amyloidosis are uniformly treated with a quadruplet combination of Dara-VCD, which was licensed for treatment for amyloidosis a few years ago. We were all thrilled but clearly, we have used all our most effective agents in frontline therapy creating some challenges when patients either don’t respond, don’t get a complete response which is still 40% of the patients or patients who relapse where we cannot use a proteasome inhibitor or we cannot use daratumumab. It’s important to remember that the patients with amyloidosis have an 11;14 translocation and 70% of patients with light chain only amyloidosis will have an 11;14 translocation. BCL2 targeted therapies with venetoclax similar agents are potential options for these patients. The BCMA directed therapies with bispecific antibodies or antibody drug conjugates will also be potential targets and there have been a number of studies retrospective studies that have come through looking at BCMA targeted agents in relapsed AL. There is a poster here looking at elranatamab in patients with stage 3 cardiac amyloidosis showing that it is tolerable, it’s very well deliverable with no treatment-related mortality and very deep responses. So I do believe that these targeted immunotherapies may be the future of patients with amyloidosis who relapse following treatment with Dara-VCD either with a BCL2 target for the 11;14 or a BCMA target for all the others.

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