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EHA 2025 | Can anti-CD38 therapies be retained in treatment rotations for myeloma following relapse?
Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, MA, discusses the role of CD38 monoclonal antibodies in subsequent lines of therapy for patients with multiple myeloma (MM) who relapse following upfront CD38-directed treatment. Dr Richardson mentions the Phase II ISABELA trial (NCT05922501), in which a quadruplet regimen of isatuximab, belantamab mafodotin, pomalidomide, and dexamethasone has shown promising results in patients previously treated with daratumumab-based therapy. This interview took place at the 30th Congress of the European Hematology Association (EHA) in Milan, Italy.
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Transcript
And the issue is that daratumumab now is really used up front and is now you know most recently looks like it will be fully approved for the use for its use in high-risk smoldering myeloma. When you’ve got widespread use of CD38 monoclonal antibody therapy upfront, what’s its role in relapse? And I think it very much depends on treatment sequencing and treatment intervals and whether or not at the time of relapse, the particular patient in question is actually on a CD38 antibody...
And the issue is that daratumumab now is really used up front and is now you know most recently looks like it will be fully approved for the use for its use in high-risk smoldering myeloma. When you’ve got widespread use of CD38 monoclonal antibody therapy upfront, what’s its role in relapse? And I think it very much depends on treatment sequencing and treatment intervals and whether or not at the time of relapse, the particular patient in question is actually on a CD38 antibody. So I think bearing all of those factors in mind, certainly in our own practice, we’ve been exploring isatuximab upfront and therefore using daratumumab in later relapse and vice versa. For patients in our practice who received daratumumab-based therapy early, what’s the role for isatuximab in relapse? And we’re seeing important response signals, but I think one has to be careful about immediately following when, say, for example, daratumumab-based therapy upfront has failed a patient, then coming straight in with an isatuximab-based platform. And I say that only because I think there are so many good other options. And so, for example, the use of a BCMA-based platform then followed thereafter by, say, an isatuximab-based approach may make sense.
At our own center, however, we’re doing a very interesting study called ISABELA, led by my colleague Andy Yee, where we’re combining isatuximab, belantamab with pomalidomide and dexamethasone, a quadruplet of drugs. And we’re using that, and you can have had prior daratumumab-based therapy, but our only requirement is that you’re not actually refractory to daratumumab when you come onto the trial. Suffice to say, a number of my patients have participated in that trial. They’ve had prior daratumumab. Actually, I’m very pleased to say they’ve all responded and they’ve tolerated treatment remarkably well. But that’s obviously an integration of pomalidomide, CD38 monoclonal antibody in the form of isatuximab and belantamab mafodotin. So, you know, really interesting approach to taking on initial treatment failure.
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