Satuximab, Weekly Carfilzomib, and Dexamethasone as Salvage Therapy for RRMM

There are numerous factors to consider when selecting treatment for relapsed multiple myeloma, including treatment-related (safety and response rates) and patient-related (tolerance and convenience) considerations. Preferred are triplet-based regimens that incorporate active drug classes (PI, IMiD, and CD38 antibodies). Patients receiving isatuximab, twice-weekly high-dose carfilzomib (56 mg/m2), and dex (Isa-Kd) had a PFS of 35.7 months, according to updated IKEMA study results. The purpose of this study was to evaluate the safety and efficacy of Isa-Kd in patients with relapsed multiple myeloma by administering high-dose K (70 mg/m2) weekly. Patients were eligible if they had RRMM, had received at least one but no more than three prior lines of therapy, had not been previously exposed to CD38 antibodies, and may have received K but cannot be K-refractory.

Patients had to have sufficient blood counts and organ function. Patients received Isa 10 mg/kg IV Qwk x 4 doses, followed by ISA 10 mg/kg IV every other week, K 20 mg/m2 on C1D1, followed by K 70 mg/m2 on C1D8 and 15 and D1, 8, and 15 in subsequent 28-day cycles, and dex 40 mg Qwk. This research was designed in collaboration with the Multiple Myeloma Research Consortium, and five sites are actively recruiting participants. As of January 31, 2023, 33 patients were enrolled, and the median duration of follow-up was 9 months (range: 2.0–27). Median age is 64 years (range, 35–83; 12 patients are 70+); 20M, 13F; 34% of patients had an elevated cytogenetic risk, and an additional 22% had an isolated 1q21 gain/amp. Patients had a median of 1 prior LOT (1–3): 100% were exposed to IMiD and PI; 43% were Lenrefractory. Thrombocytopenia was the most prevalent hematologic toxicity (21%; 15% Gr2/3).

The most prevalent non-hematologic adverse reactions (incidence >20%) were hypertension (HTN) (48%: 18% Grade 3), infection (45%, 3% Grade 3), infusion reactions (39%; all Grade 1/2), lethargy (33%), dyspnea (27%), insomnia (21%), and ALT elevation (21%). Three patients experienced cardiovascular adverse events (Gr3 MI, Gr2 DVT, and Gr2 pulmonary edema). ORR was 87.5% (sCR/CR = 2, VGPR = 18, PR = 8, VGPR = 62.5%). The median time to first response was 28 days (range: 28-NR); the median DOR was not attained, and 24/33 patients still received treatment. No patient discontinued treatment due to a side effect. The combination of Isa and weekly Kd appears safe, with manageable adverse effects. Rapid responses have been observed with an ORR of 87.50% (62.5% achieving VGPR) and responses that intensify over time. These preliminary findings support using Isa-with weekly Kd in inpatients with relapsed multiple myeloma (MM).

Source: https://library.ehaweb.org/eha/2023/eha2023-congress/386731/david.h.vesole.isatuximab.weekly.carfilzomib.and.dexamethasone.as.salvage.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178

Clinical Trial: https://www.clinicaltrials.gov/study/NCT03275285

David H. Vesole, Jesus Berdeja, Jeffrey Matous, Suzanne Trudel, Henning Schade, Pamela Munster, Savannah Berkeley, Benjamin Sun, Tom Martin/ISATUXIMAB, WEEKLY CARFILZOMIB AND DEXAMETHASONE AS SALVAGE THERAPY FOR RRMM; INTERIM RESULTS FROM A PHASE 2 TRIAL./Inc, M. G. (n.d.). ISATUXIMAB, WEEKLY CARFILZOMIB, AND DEXAMETHASONE AS SALVAGE THERAPY… by David H. Vesole. Library.ehaweb.org. Retrieved July 14, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386731/david.h.vesole.isatuximab.weekly.carfilzomib.and.dexamethasone.as.salvage.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178