Xavier P. Leleu, MD, PhD, on Multiple Myeloma: Update on Isatuximab, Lenalidomide, Dexamethasone, and Bortezomib

2024 ASCO Annual Meeting


Xavier P. Leleu, MD, PhD, of France’s Université de Poitiers and Centre Hospitalier Universitaire de Poitiers, discusses phase III findings showing that isatuximab in combination with bortezomib, lenalidomide, and dexamethasone deepened responses and increased the rate of measurable residual disease negativity vs isatuximab with lenalidomide and dexamethasone in patients with newly diagnosed transplant-ineligible multiple myeloma (Abstract 7501).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The current standard of care for newly diagnosed multiple myeloma, non-transplant eligible, but non-frail, usually patients from, let's say 65 to 79, 80 years old, is a triplet-based regimen called C38 Immunotherapy first in class [inaudible] plus Lenalidomide and Dexamethasone based on a study named MAIA that was for registration. And I guess most of the country in the world now use that triplet-based combination as standard of care. It has replaced a previous one called [inaudible]. We wanted to improve on the results, the main results, the most interesting results of MAIA, meaning the MRD negative rate, 10 to -5 threshold that was at 31% approximately, and we wanted to improve as well the survival that is at median at approximately five years, 62 months. So we created this phase three study, randomized one-to-one, two arms; one arm MAIA-like, but using Isatuximab, the second-in-class immunotherapy targeting CD38. isatuximab, lenalidomide, dexamethasone in the control arm, 135 patients versus isatuximab, lenalidomide, dexamethasone plus bortezomib, a protease inhibitor, first in class that we know for years and we know is extremely efficacious in myeloma in the study arm, a quadruplet-based regimen; again, 135 patients. The primary endpoint was the MRD-negativity rate at 10 to minus five at 18 months. And I'm not going to go through the secondary endpoint, the regular safety, survival types of response and other MRD endpoints. The results of the study are that we have met primary endpoint. The rate of MRD-negativity, 10 to minus five in the control arm, ISAL index was 26% similar to MAIA. It was more than 50%, 53% in the study arm, in the quadruplet-based regimen, which not only a positive study, because it was calculated initially at 30%, and it is more than 50, but it is even more than a positive study. It is a clinically meaningful improvement in MRD-negativity rate, because more than half of the patients actually reach MRD-negativity at 10 to minus five, which is unprecedented in myeloma in that population, in non-transplant eligible patients. The survival cannot be shared yet because it is immature. All of the patient have reached 18 months, but it is too early to talk about survival. Yet the safety profile was as expected; it was of course good, manageable. The bortezomib in that study was given weekly, so we have a lot improve the risk of side effects related to bortezomib. However, I have to disclose a slight increase in neurotoxicity. But overall, it was a quadruped regimen with a very interesting balance risk-benefit, given the incredible activity and given the slight increase in neurotoxicity in terms of safety profile. And so we believe that isatuximab, bortezomib, lenalidomide, dexamethasone, quadruped based regimen is the new standard of care and probably should replace the triple-based regimen that we were using before.

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