P902: isatuximab, weekly carfilzomib and dexamethasone as salvage therapy for rrmm; interim results from a phase 2 trial.

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: There are many considerations when selecting treatment for relapsed MM including treatment-related (safety and response rates) and patient-related (tolerability and convenience) factors. Triplet-based regimens that combine active classes of drugs (PI, IMiD and CD38 antibodies) are preferred. Updated results from the IKEMA study reported a PFS of 35.7 months in patients receiving isatuximab, twice weekly high-dose carfilzomib(56mg/m2) and dex(Isa-Kd). Aims: The aim of this study was to assess the safety and efficacy of Isa-Kd utilizing once weekly high-dose K (70 mg/m2) in patients with relapsed multiple myeloma. Methods: Eligible pts had RRMM, received at least 1 but no more than 3 prior lines of therapy, had no prior exposure to CD38 antibodies and could have received K but could not be K refractory. Patients were required to have adequate blood counts and organ function. Pts received standard dose Isa 10 mg/kg IV Qwk x 4 doses then ISA 10 mg/kg IV every other week, K 20 mg/m2 on C1D1 then K 70 mg/m2 C1D8 and 15 and on D1, 8, 15 in subsequent 28-day cycles, and dex 40 mg Qwk. This study was developed in cooperation with the Multiple Myeloma Research Consortium and 5 sites are actively enrolling subjects. Results: As of January 31, 2023; 33 patients have been enrolled, median follow-up is 9 mo (range, 2.0–27). Median age is 64 y (range, 35–83; 12pts 70+); 20M, 13F; 34% of pts had high cytogenetic risk and an additional 22% had isolated 1q21 gain/amp. Pts had a median of 1 prior LOT (range, 1–3): 100% IMiD and PI exposed; 43% Len refractory. The most common hematologic toxicity was thrombocytopenia (21%; 15% Gr2/3). The most common non-hematologic adverse events (incidence >20%) were hypertension (HTN) (48%: 18% Gr3), infection (45%, 3% Gr3), infusion reactions (39%; all Gr 1/2), fatigue (33%), dyspnea (27%), insomnia (21%) and ALT elevation (21%). Cardiovascular AE’s were seen in 3 patients (Gr3 MI, Gr2 DVT, Gr2 pulmonary edema). The ORR was 87.5% (sCR/CR 2, VGPR 18, PR 8; 62.5% ≥VGPR). Median time to first response was 28 days (range 28-NR); median DOR was not reached and treatment is on-going in 24/33. No patients discontinued therapy due to an adverse event. Summary/Conclusion: The combination of Isa + weekly Kd appears safe with manageable side effects. Rapid responses have been seen with an ORR of 87.55% (62.5% achieving ≥VGPR) and responses deepening over time. No unexpected safety signals have been noted and these early results support the use of Isa-with weekly Kd in patients with relapsed MM. Keywords: Multiple myeloma, Myeloma