Results of a multicohort, phase 1/2 study indicated that the novel cereblon E3 ligase modulator iberdomide plus dexamethasone and daratumumab, bortezomib, or carfilzomib was associated with a tolerable safety profile and promising antitumor activity in patients with heavily pretreated RRMM.
An ongoing, multicohort, phase 1/2 study (CC-220-MM-001; NCT02773030) evaluated the maximum tolerated dose, recommended phase 2 dose, safety, and preliminary antitumor activity of the novel cereblon E3 ligase modulator iberdomide plus dexamethasone and daratumumab (IberDd), bortezomib (IberVd), or carfilzomib (IberKd) in patients with relapsed/refractory multiple myeloma (RRMM). Results of the 3 independent cohorts were presented at the 2021 International Myeloma Workshop and summarized here.
The study enrolled patients with RRMM who had disease progression ≤60 days from last therapy and had received ≥2 (IberDd and IberKd cohorts) or ≥1 previous regimens (IberVd cohort) containing lenalidomide or pomalidomide and a proteasome inhibitor. Eligible patients received escalating oral doses of iberdomide administered on days 1 to 21 of each 28-day cycle in the IberDd and IberKd cohorts (with weekly carfilzomib), and on days 1 to 14 of each 21-day cycle in the IberVd cohort. The data cutoff date for this analysis was April 8, 2021.
At data cutoff, a total of 43 patients received IberDd, 25 patients received IberVd, and 9 patients received IberKd. Median age was 67 years for the IberDd cohort, 64 years for the IberVd cohort, and 61 years for the IberKd cohort. Median time since diagnosis was 7.35, 7.1, and 6.7 years, respectively. Extramedullary plasmacytomas were present in 7 (16%) patients in the IberDd cohort, 4 (16%) patients in the IberVd cohort, and 2 (22%) patients in the IberKd cohort. All patients were refractory to their last regimen; ≥33% of patients in each cohort were triple-class refractory. Median follow-up was 4.17 months for the IberDd cohort, 4.86 months for the IberVd cohort, and 5.03 months for the IberKd cohort; median cycles received were 4, 6, and 5, respectively.
Treatment-emergent adverse events (TEAEs) were mostly hematologic toxicities; incidence of nonhematologic TEAEs was low in general. Grade 3/4 nonhematologic TEAEs were fatigue, rash, and gastrointestinal disorders. Hematologic grade 3/4 TEAEs of interest included neutropenia (67%), leukopenia (23%), anemia (21%), and febrile neutropenia (5%) with IberDd; neutropenia (28%) and thrombocytopenia (24%) with IberVd; and lymphopenia (44%) and neutropenia (33%) with IberKd. Neutropenia was managed with growth factor support using granulocyte colony-stimulating factor.
Patients who received IberDd achieved an overall response rate (ORR) of 46% and very good partial response (VGPR) or better of 24%; those who received IberVd achieved an ORR of 56% and VGPR or better of 28%; and those who received IberKd achieved an ORR of 50% and VGPR or better of 38%. Median time to response was similar between cohorts (IberDd, 4.1 weeks; IberVd, 3.6 weeks; IberKd, 4.1 weeks). Median duration of response was not reached in the IberDd cohort, 35.7 weeks in the IberVd cohort, and not reached in the IberKd cohort. Recommended phase 2 dose was determined at 1.6 mg in the IberDd cohort; dose evaluation continues in the other 2 cohorts.
Results of this phase 1/2 study indicated that the iberdomide-based treatment combinations of IberDd, IberVd, and IberKd showed a tolerable safety profile and promising antitumor activity in patients with heavily pretreated RRMM.
Source: Lonial S, Richardson PG, Popat R, et al. Iberdomide (IBER) in combination with dexamethasone (DEX) and daratumumab (DARA), bortezomib (BORT), or carfilzomib (CFZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Clin Lymphoma Myeloma Leuk. 2021;21(suppl 2):S9.
