Continued Trials for Iberdomide in Combination Therapy for Resistant Myeloma
Posted: Wednesday, February 3, 2021
The results of a phase I/II study of combinations including the novel agent iberdomide have shown enough activity and safety in patients with relapsed or refractory multiple myeloma to develop phase III trials with iberdomide-based regimens. Niels W.C.J. Van de Donk, MD, PhD, of Cancer Center Amsterdam in the Netherlands, and colleagues presented their work on iberdomide during the virtual edition of the 2020 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 724). Iberdomide is an oral cereblon E3 ligase modulator agent, and in preclinical models, it had synergistic tumoricidal and immune-stimulatory effects when combined with daratumumab or bortezomib.
These particular results focused on heavily pretreated patients now receiving dexamethasone plus escalating doses of iberdomide, along with either daratumumab (n = 19) or bortezomib (n = 21). All patients had experienced disease progression on or within 60 days of their last multiple myeloma therapy. The researchers’ primary objectives were to evaluate the maximum tolerated dose, recommended phase II dose, and safety separately for each cohort, with preliminary assessment of efficacy as a key secondary objective.
Both cohorts received iberdomide doses ranging from 1.0 to 1.6 mg, but in neither one has the maximum tolerated dose or recommended phase II dose been reached. More than half of the patients in each cohort (daratumumab, 53%; bortezomib, 62%) continue on treatment. The clinical benefit and disease control rates in the two cohorts were 47%/88% and 65%/85%, respectively. Although grade 3 or 4 treatment-emergent adverse events occurred in 78% and 65% of patients, respectively, the investigators deemed the regimens to have favorable tolerability.
“Immune-profiling data confirm that iberdomide plus dexamethasone was pharmacodynamically active in triplet combination and not augmented by the addition of daratumumab or bortezomib,” Dr. Van de Donk and colleagues concluded. The ongoing study is continuing enrollment at the 1.6-mg dose level for both cohorts.
Disclosure: The study authors’ disclosure information can be found at ash.confex.com.
