EHA 2021 | Update on iberdomide treatment combinations in R/R myeloma
Niels van de Donk, MD, PhD, VU University Medical Center, Amsterdam, The Netherlands, gives an update on the Phase I/II trial (CC-220-MM-001) investigating the use of iberdomide and dexamethasone with either daratumumab (IberDd), bortezomib (IberVd), or carfilzomib (IberKd) to treat relapsed or refractory (R/R) myeloma. The most common adverse effect was neutropenia, with other adverse effects such as lymphopenia and thrombocytopenia being associated with at least one of the three treatment combinations. The overall response rate was 41% for IberDd, 58% for IberVd, and 57% for IberKd. The recommended Phase II dose (RP2D) was 1.6mg for IberDd. RP2D for IberVd and IberKd has not yet been determined. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
We presented an update last EHA about iberdomide. In this Phase I/II study patients were treated with either iberdomide as a monotherapy or iberdomide with dexamethasone, or iberdomide-dexamethasone with a third drug, either bortezomib, daratumumab, or carfilzomib. And at this EHA meeting, we had an update focused on the efficacy and safety data of the triplets.
So, in this study, heavily pretreated patients were enrolled, approximately one third of these patients were triple-class refractory, so refractory to an IMiD, a proteasome inhibitor and a CD38 antibody...
We presented an update last EHA about iberdomide. In this Phase I/II study patients were treated with either iberdomide as a monotherapy or iberdomide with dexamethasone, or iberdomide-dexamethasone with a third drug, either bortezomib, daratumumab, or carfilzomib. And at this EHA meeting, we had an update focused on the efficacy and safety data of the triplets.
So, in this study, heavily pretreated patients were enrolled, approximately one third of these patients were triple-class refractory, so refractory to an IMiD, a proteasome inhibitor and a CD38 antibody. And when we look at the safety data across these triplet cohorts, I think it’s important to mention that hematologic toxicity was infrequently observed and also grade 3-4 and non-hematologic events were uncommon. So, few rash, few gastrointestinal events, and that’s important when it comes to quality of life.
When we look at the efficacy of iber-dara-dex in the 37 response evaluable patients, then the overall response rate was 46%, which is quite high because a substantial proportion of these patients was pretreated and refractory to daratumumab. When we look at the 25 response evaluable patients treated with iber-Velcade-dex, then the overall response rate was 56%. And again, also here, there was a substantial proportion of patients that was refractory to proteasome inhibitors. And finally, there were 8 response evaluable patients that were treated with iber-carfilzomib-dexamethasone, and in this cohort of patients, the overall response rate was 50%. And again, most of these patients were refractory to previous therapy with a proteasome inhibitor.
So, in conclusion, I think we can say from these triplet cohorts that iber with dara-dex, with bor-dex or with carfilzomib-dex is showing a favorable safety profile and also a promising efficacy profile in heavily pretreated patients. And these data further support the development of iber-based regimens in myeloma, including the application of iberdomide in earlier phases of the disease. And indeed, several Phase III and Phase II studies are planned in patients with early relapse or with newly diagnosed disease, for example, as a maintenance post-transplant.
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Disclosures
Niels van de Donk, MD, PhD, has received research support from Janssen Pharmaceuticals, AMGEN, Celgene, Novartis, and BMS; and serves in advisory boards for Janssen Pharmaceuticals, AMGEN, Celgene, BMS, Takeda, Roche, Novartis, Bayer, and Servier.
