Treatment with carfilzomib-melphalan-prednisone (KMP) did not result in significantly different progression-free survival (PFS) compared with bortezomib-melphalan-prednisone (VMP) in patients with transplant-ineligible, newly diagnosed multiple myeloma. These results from the phase 3 CLARION trial (ClinicalTrials.gov Identifier: NCT01818752) were published in Blood.

In CLARION, 955 patients were randomly assigned in a 1-to-1 ratio to receive KMP or VMP for 9 cycles that were 42 days long. In the intention-to-treat population, 478 patients were in the KMP arm, and 477 were in the VMP arm.

Median PFS was 22.3 months in the KMP arm and 22.1 months in the VMP arm (hazard ratio [HR], 0.906; 95% CI, 0.746-1.101; P =.159).

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Median overall survival was similar and not reached in both treatment arms (HR, 1.08; 95% CI, 0.82-1.43). The overall response rate was 84.3% for the KMP arm and 78.8% for the VMP arm. The complete response rate was 25.9% in the KMP arm and 23.1% in the VMP arm. Minimal residual disease-negative rates were 15.7% in the KMP arm and 15.5% in the VMP arm.

All-grade adverse events (AEs) of interest occurring with at least a 5% incidence in the KMP arm were acute renal failure (13.9% vs 6.2% in VMP) and cardiac failure (10.8% vs 4.3% in VMP).

Rates of grade 3 or greater AEs were 74.7% in the KMP arm and 76.2% in the VMP arm. Peripheral neuropathy of at least grade 2 was lower in the KMP arm (2.5%) compared with the VMP arm (35.1%).

“Increased toxicity in the carfilzomib group of CLARION may explain clinical outcomes, and melphalan may not be an ideal drug to combine with carfilzomib in this setting,” the authors concluded. “Alternative carfilzomib-based regimens merit further evaluation in patients with newly diagnosed multiple myeloma.”

Reference

1.     Facon T, Lee JH, Moreau P, et al. Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma [published online May 2, 2019]. Blood. doi:10.1182/blood-2018-09-874396