IMS 2025 | AFT-41 trial: daratumumab, lenalidomide, ixazomib, and dexamethasone in transplant-ineligible NDMM

So the Alliance Foundation Trial 41 is a Phase II trial looking at a four-drug regimen for newly diagnosed older transplant-ineligible patients. So the components of this four-drug regimen, they’re now an established part of myeloma care. And we think about the four components being anti-CD38 monoclonal antibodies, immunomodulatory drugs, proteosome inhibitors, and dexamethasone. What makes our trial unique and a contribution to myeloma care is that we designed this trial specifically for older transplant-ineligible patients. The trials that we’ve already heard about for transplant-ineligible patients, they essentially are taking a regimen aimed at younger patients and more or less using the same regimen for our older patients. We figured, how can we use what we learned, for example, with our experience with the RVd light regimen, where we used, for example, a lower dose of lenalidomide and spacing out the interval between bortezomib to improve the tolerability? How can we take the learnings from that and apply it for our transplant-ineligible patients. So with AFT41, we used a lower dose of lenalidomide and we replaced the proteasome inhibitor with the oral proteasome inhibitor, ixazomib. Now ixazomib has several advantages. One, it has significantly less risk of peripheral neuropathy, which can be a significant limitation of the proteasome inhibitor, bortezomib. So less neuropathy. And then number two, it’s an oral medication. Because it’s an oral medication, it allows patients the ability to be on this therapy for extended periods of time. Whereas that could be a challenge for a patient to continuously come in for dosing with bortezomib since it’s given in the clinic. So when using this four-drug regimen, what we were able to show in this trial based on the first 12 cycles of therapy, which was, so what we presented today was the interim analysis of the first 12 cycles, we showed response rates that are comparable to what we’ve seen already with other four-drug regimens. So I think that’s a really promising step forward to be able to take this more user-friendly regimen and achieve similar response rates for our older, frailer patients.

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