Weekly Carfilzomib, Pomalidomide, and Dexamethasone Demonstrates Efficacy for Patients With R/R Multiple Myeloma
Phase 2 Results from the SELECT Study
Phase 2 Results from the SELECT Study
Results of an open-label, phase 2 study demonstrated that once-weekly carfilzomib at 56 mg/m2 plus immunomodulatory drugs and dexamethasone showed efficacy and tolerability in treating patients with early relapsed/refractory (R/R) multiple myeloma (MM).
A gap currently exists in addressing therapy for many patients with double- or triple-class refractory R/R MM at first or second relapse,” according to Aurore Perrot, MD, PhD, Paul Sabatier University: Toulouse, France.
The phase 2 SELECT study evaluated the efficacy and safety of weekly carfilzomib, pomalidomide, and dexamethasone among patients with early R/R MM who were refractory to lenalidomide. The primary end point was overall response rate (ORR), defined as an achievement of partial response (PR), very good PR (VGPR), complete response (CR), or stringent complete response (sCR), according to International Myeloma Working Group (IMWG)-Uniform Response Criteria and was determined by an independent review committee (IRC).
Eligible participants included those ≥ 18 years old had R/R MM after receiving 1 to 2 prior treatment regimens and were refractory to lenalidomide with measurable disease. Patients were required to have had at least a partial response (PR) to 1 prior line of therapy and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Carfilzomib was administered intravenously over 30 plus-or-minus 5 minutes on days 1, 8, and 15 (plus-or-minus 2 days) of each 28-day cycle for up to 12 cycles or progression, then on days 1 and 15 for cycle 13 and beyond, and continuing until disease progression or end of study. Additionally, a dose of 20 mg/m2 was administered on day 1 of cycle 1, and all subsequent doses were 56 mg/m2. Pomalidomide was given at 4 mg/day orally on days 1 to 21 of each cycle. Dexamethasone was administered at least 30 minutes to 4 hours before carfilzomib on days carfilzomib was administered. Dexamethasone was administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle up to cycle 12 and at a dose of 20 mg on days 1 and 15 during cycle 13 onward. For patients ≥75 years old, the dose was reduced to 20 mg during cycles 1 to 12 and 10 mg from cycle 13 onward.
Investigators included 52 patients who received at least 1 dose of carfilzomib and were included in the primary analysis. Overall, 75% of patients were disease refractory to prior lenalidomide and daratumumab-containing regimen, including 38% of patients who were double-class refractory ([immune-mediated inflammatory diseases] IMiD and anti-CD38), and 37% of patients who were triple-class refractory (IMiD, PI, and anti-CD38).
Results demonstrated at the data cutoff of November 2022, the study did not meet its primary end point, with an ORR among all patients of 58% (90% [confidence interval] CI, 45.4 to 69.3; 35% ≥ very good partial response, 6% ≥ complete response) with a median response duration of 20.3 months. It was noted that minimal residual disease negativity (10 to 5) was achieved in 10% of patients. The median progression-free survival (PFS) was 11.1 months, and the median overall survival (OS) was 18.8 months.
All-grade treatment-emergent adverse events were reported in 94% of patients, with grade ≥3 adverse events reported in 67% of patients. The most frequently reported grade ≥3 adverse events were hematologic. Including neutropenia (27%), anemia (13%), and thrombocytopenia (13%). It was also noted that the most frequent non-hematologic grade ≥3 adverse events were acute kidney injury, rash, asthenia, and respiratory failure, reported in 3 patients (6%) each.
Perrot and colleagues noted, “Although the primary end point of ORR was not met, [carfilzomib, pomalidomide, and dexamethasone] showed meaningful clinical benefits in lenalidomide-refractory [R/R] MM patients, including those who were daratumumab-refractory and/or triple-class refractory.
“The results of SELECT suggest that [carfilzomib, pomalidomide, and dexamethasone] is a safe and effective regimen that may be appropriate for a growing number of patients with relapsed MM,” they concluded.
Source:
Perrot A, Delimpasi S, Spanoudakis E, et al. An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study. Leuk & Lymph. Published online March 18, 2024. doi: 10.1080/10428194.2024.2322030
