Efficacy and Tolerability of Weekly Bortezomib, Lenalidomide, and Dexamethasone Protocols in Transplant-Ineligible Newly Diagnosed Myeloma: An Australian Real-World, Multicenter Study

Background: Lenalidomide, bortezomib, and dexamethasone (RVD) remains a standard of care regimen for newly diagnosed multiple myeloma in centers without access to upfront anti-CD38 therapy within the Asia-Pacific. However, regimens proven efficacious in clinical trials utilize twice-weekly bortezomib, which is now thought to confer unacceptable toxicity, particularly in transplant-ineligible patients. There is a paucity of prospective data on RVD treatment schedules utilizing weekly bortezomib, which has implications for health care systems implementing standardized treatment based on clinical trial evidence. Methods: Eighty-three patients with newly diagnosed transplant-ineligible multiple myeloma from six hospitals in Australia, received one of two RVD regimens utilizing weekly subcutaneous bortezomib (Modified SWOG and Modified RVD Lite) pragmatically adapted from their corresponding clinical trials. Baseline characteristics, response rates, toxicities, and survival were assessed. Results: At a median follow-up of 27.4 months, Modified SWOG achieved an ORR 91.4%, ≥ VGPR 71.4%, and 24-month progression-free survival (PFS) of 63.1% (95% CI: 47.6–83.5). Modified RVD Lite achieved an ORR 93.9%, ≥ VGPR 64.7%, and 24-month PFS of 53.6% (95% CI: 39.1–73.4). Despite dose attenuation, significant toxicity was still seen overall with hospitalizations in 48.2% and premature cessation due to toxicity in 31.3%. Peripheral sensory neuropathy was lower than in published clinical trials, reported in 32 (38.6%) patients, with Grade 3 events in only 2 patients. Conclusion: This study demonstrates that real-world outcomes of weekly RVD regimens have comparable efficacy to published twice-weekly regimens; however, toxicity remains a significant challenge in this patient population.