The US Food and Drug Administration granted accelerated approval to iberdomide (ZENBEXUS) with daratumumab and hyaluronidase-fihj and dexamethasone in adults with multiple myeloma who had received at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent, according to a press release from Bristol Myers Squibb. According to the company, iberdomide is the first cereblon E3 ligase modulator to receive US Food and Drug Administration approval and is part of the cereblon-modulating protein degrader class used to treat multiple myeloma.
The approval was based on results from the phase 3 EXCALIBER-RRMM trial, which compared iberdomide, daratumumab and hyaluronidase-fihj, and dexamethasone (ZDd) with daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma. At a median follow-up of 16 months, 41% of patients receiving ZDd achieved minimal residual disease (MRD)-negative complete response compared with 21% receiving DVd. MRD-negative complete response was one of the trial’s dual primary endpoints.
EXCALIBER-RRMM is an ongoing, multicenter, randomized, open-label trial. Eligible patients had progressive disease and had recieved one to two prior lines of antimyeloma therapy. A total of 939 patients were randomized. The primary efficacy population for MRD negativity included the first 420 patients randomized, with 207 assigned to ZDd and 213 to DVd. Treatment continued until disease progression or unacceptable toxicity. The trial continues to evaluate progression-free survival,the second dual primary endpoint.
Among patients receiving ZDd, 90% experienced neutropenia and 79% experienced infections. Eight percent discontinued ZDd because of adverse reactions. Serious adverse reactions occurred in 58% of patients receiving the iberdomide-containing regimen. These included pneumonia in 26%, upper respiratory tract infection in 6%, second primary malignancy in 6%, neutropenia in 5%, COVID-19 in 4%, febrile neutropenia in 4%, and sepsis in 3%. Fatal adverse reactions occurred in 10 patients (5%) receiving the iberdomide-containing regimen.
Iberdomide carries boxed warnings for embryo-fetal toxicity and serious venous and arterial thromboembolism and is contraindicated in females who are pregnant. The prescribing information recommends antithrombotic prophylaxis and monitoring for signs and symptoms of thromboembolic events during treatment. Because of the risk of embryo-fetal toxicity, iberdomide is available only through the restricted ZENBEXUS REMS program.
Continued approval may depend on confirmatory evidence of clinical benefit.
Source: Bristol Myers Squibb
