A phase 2 study of isatuximab added to weekly carfilzomib, lenalidomide, and dexamethasone demonstrated promising efficacy and safety in transplant-eligible patients with newly diagnosed multiple myeloma.
Isatuximab is a novel CD38 monoclonal antibody being studied in a variety of novel combination strategies. SKylaRk is a phase 2 trial evaluating the addition of isatuximab to weekly carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in all-risk, transplant-eligible patients with newly diagnosed multiple myeloma. Elizabeth K. O’Donnell presented results from this phase 2 trial at the 2022 American Society of Hematology meeting.
A total of 50 eligible patients received 4 cycles of induction therapy with Isa-KRd followed by investigator’s choice of upfront versus deferred stem-cell transplant (SCT). Patients undergoing SCT received 2 additional cycles of therapy and then maintenance therapy, and patients deferring SCT received an additional 4 cycles of therapy and then maintenance therapy. Patients were stratified by cytogenetics for maintenance therapy; patients with standard-risk cytogenetics received lenalidomide, and patients with high-risk cytogenetics received isatuximab, carfilzomib, and lenalidomide. Twenty-three patients had high-risk cytogenetics (including deletion 17p, gain of 1q, and translocations t[4:14], t[14;16], and t[14;20]). Forty-seven patients were evaluable for response after 4 cycles, and the overall response rate (ORR) was 94%; 84% achieved a very good partial response (VGPR) or better and 38% achieved a complete response (CR). Minimal residual disease (MRD) results were available for 28 patients after 4 cycles who achieved a VGPR or better, and 43% were MRD negative at 105. After 8 cycles of therapy, ORR was 100%, 95% of patients achieved a VGPR or better, 67% achieved a CR, and 74% of evaluable patients achieved MRD negativity. Five patients elected to go with upfront transplant, and the ORR was 100%. The 15-month progression-free survival was 88.6%, and the 15-month overall survival was 98%. The most common grade 3 or 4 adverse events were neutropenia (28%), elevated alanine aminotransferase (14%), anemia (10%), hypertension (8%), thrombocytopenia (6%), acute kidney injury (6%), and fatigue (6%).
These data showed promising results with Isa-KRd, with an ORR of 100% and predictable safety profile.
- O’Donnell EK, Mo CC, Nadeem O, et al. A phase II study of once weekly carfilzomib, lenalidomide, dexamethasone, and isatuximab in newly diagnosed, transplant-eligible multiple myeloma (The SKylaRk Trial). Presented at: 2022 American Society of Hematology Annual Meeting; December 10-13; New Orleans, LA. Abstract 3239.