Mezigdomide plus carfilzomib and dexamethasone improved progression-free survival in relapsed/refractory multiple myeloma.
The addition of mezigdomide (CC-92480) to carfilzomib (Kyprolis) and dexamethasone (Kd) led to a statistically significant improvement in progression-free survival (PFS) compared with Kd alone in patients with relapsed/refractory multiple myeloma, meeting the primary end point of the phase 3 SUCCESSOR-2 trial (NCT05552976).1
Safety data for mezigdomide plus Kd were consistent with the known safety profile of the CELMoD and the combination regimen. Data from SUCCESSOR-2 will be presented at an upcoming medical conference and shared with global health authorities.
“While treatment advances have been meaningful, far too many patients with multiple myeloma still relapse or stop responding—making the need for new options urgent,” Paul Richardson, MD, director of Clinical Research and Clinical Program leader at the Jerome Lipper Multiple Myeloma Center of the Dana-Farber Cancer Institute and the RJ Corman Professor of Medicine at Harvard Medical School, stated in a news release. “These data underscore the potential of mezigdomide plus Kd as an oral regimen that could address a key unmet need for patients previously exposed to anti-CD38 and lenalidomide [Revlimid].”
Mezigdomide is a CELMoD designed to alter the conformation of cereblon within the CRL4CRBN E3 ubiquitin ligase complex, leading to the recruitment of novel protein substrates for selective proteasomal degradation.2
Regarding safety, at a median of 4 treatment cycles (range, 1-20), common any-grade adverse effects comprised neutropenia (77%), infection (65%), anemia (52%), thrombocytopenia (43%), and febrile neutropenia (15%).
SUCCESSOR-2 was a phase 3, 2-stage, randomized, multicenter, open-label trial that enrolled patients at least 18 years of age with multiple myeloma with measurable disease.4 At least 1 prior line of therapy for multiple myeloma was required for enrollment, including prior treatment with lenalidomide and at least 2 cycles of an anti-CD38 monoclonal antibody, and patients needed to have documented disease progression during or after their most recent line of therapy. Notably, a minimal response or better to at least 1 prior line of therapy was required.
Patients were excluded if they received prior treatment with mezigdomide or carfilzomib; or underwent allogeneic stem cell transplant at any time or autologous stem cell transplant within 12 weeks of beginning study treatment.
Enrolled patients were randomly assigned to receive mezigdomide plus Kd or Kd alone.
Along with the primary end point of PFS, secondary end points included overall survival, ORR, very good partial response or better rate, complete response or better rate, time to response, DOR, time to progression, time to next treatment, time to second progression, minimal residual disease–negativity rate, safety, and quality of life.
“It is important for patients to have treatment options that offer enduring disease control,” Meletios-A. (Thanos) Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, added in a news release.1 “These positive interim data show that adding mezigdomide, a CELMoD specifically optimized for enhanced myeloma cell killing and immune activation compared with immunomodulatory agents, to carfilzomib and dexamethasone may provide clinical benefit in earlier relapse.”
