KD-027

The second-generation proteasome inhibitor carfilzomib produces superior outcomes in relapsed or refractory multiple myeloma (MM). We conducted a single-arm trial of twice-weekly carfilzomib (27 mg/m²)-dexamethasone (Kd27) for relapsed and refractory MM in China. Kd27 was administered in 28-day cycles to 123 patients previously treated with ≥ 2 other regimens, including treatment with bortezomib and an immunomodulatory drug, and refractory to their most recent therapy. Overall response rate (ORR) was the primary endpoint; progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Primary analysis was conducted when all patients received ≥ 6 cycles of Kd27 or discontinued Kd27. Median age was 60 years; median number of prior regimens was 4; 74% were refractory to proteasome inhibitors and immunomodulatory drugs. ORR was 35.8% (95% CI 27.3-44.9), median PFS was 5.6 (95% CI 4.6-6.5) months, and median OS was 16.6 (95% CI 12.2-NE) months. Grade ≥ 3 adverse events (AEs) occurred in 76.4% of patients. Grade ≥ 3 AEs of interest included hypertension (13.8%), acute renal failure (3.3%), cardiac failure (0.8%), ischemic heart disease (0.0%), and peripheral neuropathy (0.0%); 5.7% of patients discontinued carfilzomib due to AEs. Carfilzomib-dexamethasone produced a clinically meaningful response without new safety findings in Chinese patients with previously treated MM.Trial registration: NCT03029234.

In the US, carfilzomib 70 mg⁄m² once-weekly plus dexamethasone (Kd70 QW) was recently indicated for relapsed and/or refractory multiple myeloma. In current US clinical practice, most patients treated with Kd receive carfilzomib at a previously approved dose of 27 mg/m² twice-weekly (Kd27 BIW). This analysis assessed the cost-effectiveness (CE) of Kd70 QW vs Kd27 BIW regimens which were compared in the randomized phase 3 ARROW trial.

Based on clinical outcomes (overall survival and utilities) from ARROW, a partitioned survival model was developed to estimate life years (LYs) and quality-adjusted life years (QALYs). Long-term survival was extrapolated using SEER registry data matched to ARROW patients. Costs were estimated using a US healthcare payer perspective.

The analysis estimated that treatment with Kd70 QW vs Kd27 BIW resulted in an increase of 1.10 LYs, 0.91 QALYs, and additional lifetime costs of $74,858, yielding an incremental CE ratio (ratio of incremental costs to QALYs) of $82,257 per QALY gained. Results were robust to sensitivity and subgroup analyses.

When compared with Kd27 BIW, Kd70 QW is the optimal dose that represents a cost-effective utilization of health care budget with incremental CE ratios well below the accepted willingness-to-pay thresholds in the US.