What is the Response and Safety Profile With Iberdomide-Based Therapies in Multiple Myeloma?

Announcer:
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.

Dr. Mateos:
Hello to everyone. My name is Maria Victoria Mateos, from the University Hospital of Salamanca in Spain. And during the presentation I will cover what is the response as well as what is also the safety profile of Iberdomide-based therapy in relapse and refractory patients with multiple myeloma.

Iberdomide monotherapy was evaluated as part of the cohort A in the CC-220-MM-001 clinical study. And the objective was to try to evaluate the safety profile with a different dose of Iberdomide as monotherapy. But the efficacy was subsequently evaluated in combination with dexamethasone in the cohort B of these clinical studies, in which 66 relapsing on refractory myeloma patients after the median of five prior lines of therapy. And 76% of the patients were refractory to lenalidomide and 56% were refractory to Pomalidomide were included. And indeed they receive Iberdomide doses ranging from 0.3 to 1.6. 1.6 milligrams was the recommended phase two dose but just in this cohort B of patients, it was observed whether Iberdomide plus dexamethasone was effective. Even in this population, majority of them refractory to Pomalidomide and Lenalidomide. The overall response rate was 32%. The clinical benefit rate was of approximately 50% and the disease control rate was observed in 85% of the patients. But in addition to the efficacy the safety profile reported to be quite acceptable with grade three, four neutropenia in 20% of the patients and important, no grade three, four fatigue was reported.

And this results were subsequently confirmed in two additional cohorts of patients included in the phase two of this clinical study, cohort D and cohort I. And in this two cohorts of patients, relapse and refractory myeloma patients were included but in the cohort D, patients after the median over three prior lines of therapy and refractory to an IMiD API and an anti-CD38 monoclonal antibody were included. But in the cohort I, it's important to remark how patients included in this cohort and treated with Iberdomide and dexamethasone had been in in addition previously exposed to BCMA targeted therapy. This cohort of patients is extremely important because this represents the next and mathematical need we are going to see in myeloma as soon as the BCMA targeted therapy moves to earlier lines of therapy.

107 patients were treated with Iberdomide and dexamethasone in the cohort D and 26 patients were included in the cohort of patients post BCMA. The median number of prior lines of therapy was six and seven prospectively. And when the efficacy was evaluated it was reported how the overall response rate was 26 and 25% in the cohort, D and I, respectively indicating that cover the mathematical need we have in this population with a clinical benefit rate of over 36% in the cohort D and 42% in the cohort of patients previously exposed to BCMA targeted therapy. In those patients, in which the response was observed the median durability of the response was 30 weeks. And the median progression for survival was of approximately three months with a median overall survival of approximately 46 weeks.

From the safety profile point of view is important to remark that again few hematological toxicity was reported but neutropenia grade three, four was the most relevant hematological adverse event reported in both cohorts of patients. But this did not translate in a high frequency of febrile neutropenia or severe infections. And concerning non hematological treatment emerging adverse event. It is confirmed how 23% of the patient reported any grade of fatigue, but definitely grade three, four fatigue was reported in only three patients in the cohort D and in just one patient in the cohort I. In addition, well, it is important to remark how few patients required to reduce the dose of Iberdomide because of adverse events.

With this information, it is clear how Iberdomide and dexamethasone cover the met medical need that we have in multiple myeloma. And the next step is to evaluate Iberdomide and dexamethasone plus a third agent. And this is what it is being evaluated right now In three additional cohort of patients in the same study. Iberdomide in combination with the DARA and DEX Iberdomide in combination with BORT and dexamethasone and Iberdomide in combination with Carfilzomib and Dexamethasone These three part combinations are being evaluated in relapse and refractory myeloma patients after at least two prior regime, including Lenalidomide and or Pomalidomide, as well as a protein as an inhibitor. The median number of prior lines of therapy was four, five and six respectively.

And when the efficacy was evaluated the overall response rate is around 50% in the different cohorts of patients and important to remark how some patients in the different cohorts resulted in a strange and complete response or complete response. So definitely Iberdomide and Dexamethasone and Iberdomide plus Dexamethasone plus a third agent definitely cover the unmet medical need that we have in multiple myeloma demonstrated enhanced anti proliferative antitumor and an immunostimulatory activity in this population. Definitely Iberdomide is a promising combination partner with other standard of care agents in multiple myeloma and based on the safety profile Iberdomide is set to be evaluated as part of the first line of therapy.

And indeed, when we look into the ongoing clinical studies we see how Iberdomide is being evaluated as maintenance therapy after transplant in a clinical trial endorsed by the European Myeloma Network but also some cohorts of patients in the MM-001 clinical trial are evaluating Iberdomide, Bortezomib and Dexamethasone. Iberdomide data to Dexamethasone as part of the first line of therapy. And there is already a phase three clinical study in relapse and on refractory myeloma patients combining Iberdomide with the data and DEXA and the control arm is data in combination with Bortezomib and Dexamethasone. Thank you very much for your attention and hope this summary will be of your interest.

Announcer:
You have been listening to CME on ReachMD. This activity is jointly provided by Global Learning Collaborative (GLC) and TotalCME, Inc. and is part of our MinuteCME curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/CME. Thank you for listening.