Comparative Efficacy of Bortezomib, Melphalan, and Prednisone (VMP) With or Without Daratumumab Versus VMP Alone in the Treatment of Newly Diagnosed Multiple Myeloma: Propensity Score Matching of ALCYONE and VISTA Phase III Studies

Abstract

Introduction: Bortezomib, melphalan, and prednisone (VMP) is the standard of care for transplant-ineligible newly diagnosed multiple myeloma. The phase III VISTA trial established the bortezomib dosing schedule for VMP. To mitigate bortezomib-associated toxicity, the phase III ALCYONE study of daratumumab plus VMP (D-VMP) versus VMP used modified bortezomib dosing. D-VMP demonstrated improved progression-free survival and overall response rate. Propensity score matching enables indirect comparisons by controlling for differences in baseline covariates.

Patients and methods: The efficacy and safety of both arms of ALCYONE were compared with VISTA VMP using propensity score matching. ALCYONE D-VMP and VMP patients were matched on selected baseline characteristics to VISTA VMP patients, reducing or eliminating systematic differences between treatment groups.

Results: After matching, median progression-free survival and overall response rate were comparable for ALCYONE VMP and VISTA VMP, and were significantly improved with ALCYONE D-VMP versus VISTA VMP. Rates of grade 3/4 peripheral sensory neuropathy were significantly lower for both arms of ALCYONE versus VISTA VMP, with or without matching.

Conclusion: This propensity score matching analysis demonstrates significant improvements in efficacy with ALCYONE D-VMP versus VISTA VMP and a significantly lower incidence of peripheral sensory neuropathy in both arms of ALCYONE versus VISTA VMP, although safety improvements may be due to different bortezomib administration routes (ALCYONE, subcutaneous; VISTA, intravenous).

Keywords: Daratumumab; Multiple myeloma; Propensity score matching; VISTA; VMP.