MM-313: Carfilzomib, Cyclophosphamide, and Dexamethasone (KCd) for the Treatment of Triple-Class Relapsed/Refractory Multiple Myeloma (RRMM): A Single-Institution Experience

Context Treatment options for multiple myeloma (MM) have increased in recent years, and the introduction of novel therapeutic agents, such as proteasome inhibitors (PI), anti-CD-38 monoclonal-antibodies (MoAB), and immunomodulatory drugs (IMiD), have significantly prolonged survival in patients with MM. Despite advances in treatment, outcomes remain poor for those who are triple-class refractory (refractory to one class of the following: IMiD, PI, and anti-CD38 MoAB). Objective To evaluate the clinical efficacy and tolerability of KCd in patients with triple-class relapsed/refractory multiple myeloma (RRMM). Design We performed a single-center retrospective analysis of patients with triple-class RRMM treated with KCd from June 2017 to October 2020. Patients or Other Participants Twenty-three patients with triple-class RRMM treated with KCd between June 2017 and October 2020 at the University of Kansas Medical Center were reviewed. Interventions These patients received KCd for RRMM. The regimen consisted of 28-day cycles of carfilzomib 20/36 mg/m2 IV on days 1, 2, 8, 9, 15, and 16; cyclophosphamide 300 mg/m2 IV weekly; and dexamethasone (20–40) mg orally weekly. Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes. Responses were evaluated using the IMWG criteria. Main Outcome Measures Primary endpoint was PFS and OS. Secondary endpoint was ORR. Results The median age was 54 years for those with RRMM who received KCd; 26% had IgG isotype; 39% had ISS stage III; and 43% had high-risk cytogenetics. The median number of previous lines was 6 (3–10). Out of 23 patients: 83% received ASCT prior to this treatment, and 100% were triple-class RRMM. Median number of cycles received was 4 cycles. The overall response rate (ORR) was 52%. Median progression-free survival was 4 months (95% CI=3.27 to 7.97), median overall survival was 11.9 months (95% CI: 6.97 to not reached). The most common grade ≥ 3 adverse events were thrombocytopenia 74%, anemia 61%, and neutropenia 30%. Conclusions Our single-institution experience shows that patients with triple-class RRMM can achieve an acceptable response rate using KCd, which proves it can be utilized as salvage therapy in triple-class RRMM. However, we believe that this treatment could be utilized as a bridging therapy prior to CAR-T cell treatment.