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

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). © 2020 A propensity score-matched analysis compared bortezomib, melphalan, and prednisolone (VMP) in the ALCYONE study (± daratumumab [D]) with VMP in the VISTA study because no direct comparisons are available. Results indicated a lower intensity VMP regimen such as in ALCYONE has a favorable benefit/risk profile compared with the VISTA VMP schedule and D-VMP significantly improves efficacy versus VISTA VMP. © 202

The effects of different schedules of bortezomib, melphalan, and prednisone for patients with newly diagnosed multiple myeloma who are transplant ineligible: a matching-adjusted indirect comparison

For patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible, bortezomib-melphalan-prednisone (VMP) demonstrated superior efficacy based on the VISTA trial. In subsequent trials, twice-weekly bortezomib was limited to the first cycle or completely replaced with once-weekly bortezomib to reduce toxicity. Following a systematic literature review, the efficacy and safety of modified VMP schedules (pooled data from the once-weekly bortezomib VMP arm of the GIMEMA trial and the VMP arm of the ALCYONE trial) were compared to the VISTA schedule using naïve and unanchored matching-adjusted indirect comparison (MAIC). Median progression-free survival was similar between VISTA and modified VMP (20.7 months [95% CI, 18.4–24.3] vs 19.6 months [95% CI, 18.8–21.0]). Peripheral neuropathy was significantly reduced with modified VMP versus VISTA VMP (all grades: naïve, 32.1% vs 46.8% and MAIC, 32.1% vs 46.7%; both p <.0001). These findings support a modified VMP dosing schedule for patients with NDMM who are transplant ineligible. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group