Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma

Abstract

Carfilzomib and dexamethasone (Kd) has significant activity in relapsed and refractory multiple myeloma. Kd has not previously been evaluated in newly diagnosed multiple myeloma (NDMM). We report a single-arm phase 2 study of 72 patients with NDMM to evaluate the efficacy and tolerability of Kd induction.Carfilzomib was administered in two dosing cohorts with dosing of 20/45 mg/m 2 in the first 25 patients and 20/56 mg/m 2 in the subsequent 47 patients. Carfilzomib was administered on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle, dexamethasone 20 mg was administered orally on days 1, 2, 8,9,15,16, 22 and 23. Treatment was continued to maximum response, progression of disease, or regimen intolerability. Endpoints included overall response rate (ORR), regimen toxicity and impact of carfilzomib on CD34+ stem cell collection yield. Sixty-five pts achieved at least a partial response (PR) for an ORR of 90%. The maximum response achieved was complete response or better in 5 (7%), very good partial response (VGPR) in 42 (58%), PR in 18 (25%) and stable disease in 7 pts (10%). Toxicities were predominantly low grade with 547 grade 1/2 adverse events and 44 grade ≥3 events. The rate of grade ≥3 cardiovascular adverse events was 11.1% with eight observed events. The activity of Kd described represents the highest rate of overall response and ≥VGPR for any 2-agent combination in NDMM reported to date. Kd demonstrated a safety profile consistent with previously reported carfilzomib studies.

Efficacy and Toxicity Profile of Carfilzomib-Based Regimens for Treatment of Newly Diagnosed Multiple Myeloma: A Systematic Review

“…In this single-arm phase II trial reported by Forsberg et al, 2019, 37 72 NDMM patients (high-risk cytogenetics, n=9 (27%)) with a median age of 59 years were given CFZ-dexamethasone (Cd) induction. CFZ delivered in two dosing cohorts, Cd1 20/45 mg/m 2 (n=25) and Cd2 20/56 mg/m 2 (n=47).…”

A6 Peptide-Tagged Core-Disulfide-Cross-Linked Micelles for Targeted Delivery of Proteasome Inhibitor Carfilzomib to Multiple Myeloma In Vivo

“…Clinically, carfilzomib was administered on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for MM patients. 77 Here, a similar treatment scheme was adopted for CFZ-CD, CFZ-PMs, or CFZ-A6-PMs (3 mg CFZ equiv/kg) in treating LP-1 MM-bearing nude mice. The tumor growth, survival time, and body change of mice were recorded and analyzed.…”

Carfilzomib and dexamethasone induction with lenalidomide, clarithromycin and dexamethasone consolidation and lenalidomide maintenance for newly diagnosed multiple myeloma

“…A report with in depth focus on results from the Kd induction phase of this study has been previously published. 6 2 | METHODS…”

“…Additional objectives of the study were to determine overall response rate, progression‐free survival, and regimen tolerability. A report with in depth focus on results from the Kd induction phase of this study has been previously published 6 …”