Weekly Cyclophosphamide-Bortezomib-Dexamethasone Induction Performs Comparably to Twice-Weekly Dosing with Respect to Both Response Rates and Survival after Autologous Transplant

Thirunavukarasu, Caitlin; Weber, Nicholas; Morris, Kirk; Pillai, Elango; Curley, Cameron; Butler, Jason; Kennedy, Glen

doi:10.1159/000501791

Cited by 1 publication

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“…The improved tolerability of weekly compared with twice-weekly bortezomib in the context of the VMP regimen has been well described, 20 and the ALCYONE trial 6 used biweekly bortezomib for cycles 1 to 2 followed by weekly bortezomib for cycles 3 to 9 in the VMP regimen in recognition of the difficulty of delivering twice-weekly bortezomib schedules to older patients. In the context of the VCD regimen, weekly delivery of bortezomib has been reported in transplant-eligible populations, 21 , 22 , 23 , 24 but there have only been a few small retrospective reports of a weekly VCD regimen for the initial treatment of older patients. 25 , 26 The schedule of VCD in our trial, using 4-weekly bortezomib doses in a 5-week cycle, proved highly tolerable despite the older and frail population.…”

Section: Discussionmentioning

confidence: 99%

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16

Mollee,

Reynolds,

Janowski

et al. 2024

Blood Advances

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In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard of care regimens. In a randomized trial, we tested whether similar improvements would be seen when daratumumab was added to the bortezomib, cyclophosphamide and dexamethasone (VCD) regimen. Non-transplant eligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD). 121 patients were randomized, 57 in the VCD arm and 64 in the VCDD arm. Baseline characteristics were balanced between the two arms. The median PFS was 16.8m (95%CI 15.3 - 21.7m) and 25.8m (95%CI 19.9 - 33.5) in the VCD and VCDD arms, respectively (HR 0.67, log-rank test p=0.066). In a pre-planned analysis, the estimated PFS at fixed time-points post-randomization demonstrated significantly improved PFS for the daratumumab containing arm from 18 months onwards. The proportions of patients who were progression free at the following time points were: 18 months, 48% vs 68% (p=0.0002); 24 months, 36% vs 52% (p=0.0001); and 30 months, 27% vs 41% (p<0.0001) in the VCD and VCDD arms, respectively. The best overall response and VGPR rate were significantly better in the daratumumab arm (65% vs 86%, p=0.007 and 28% vs 52%, p=0.009) for the VCD and VCDD arms, respectively. Seventy-two percent of the VCDD patients completed the 9 cycles of induction therapy with no grade 3 or 4 peripheral neuropathy adverse events. This study supports VCDD as an option for the initial treatment of non-transplant eligible patients with myeloma. Australian and New Zealand Clinical Trials Registry (ACTRN12617000202369). https://www.anzctr.org.au/

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