Long-term outcomes of modified-intensity lenalidomide, bortezomib and dexamethasone (RVD-lite) in transplant-ineligible multiple myeloma: final report of a phase II trial.

Background: We report the long-term survival outcomes of modified-intensity lenalidomide, bortezomib, and dexamethasone (RVD-lite) as frontline treatment for transplant-ineligible multiple myeloma (MM). Methods: RVD-lite was evaluated in an investigator-initiated, multicenter phase II trial in transplant-ineligible MM patients. RVD-lite was administered over a 35-day cycle with lenalidomide 15 mg orally on days 1-21; bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, 22; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, 16, 22, and 23 in patients aged £75 years and days 1, 8, 15, and 22 in patients aged >75 years for 9 cycles of induction followed by 6 cycles of consolidation (lenalidomide + bortezomib). Lenalidomide maintenance was not mandated. Results: Fifty patients were enrolled. Median age was 73 years (range 65-91), and 14% of patients had an ECOG performance status of 2. At best response, the ORR and ³VGPR were 90% and 66%, respectively. After median follow-up of 72 months, the median PFS was 42 months (5-year PFS: 40%), and the median OS was 76 months (5-year OS: 63%). ECOG performance status of 2 was associated with inferior PFS and OS. Thirty-three patients (66%) received lenalidomide maintenance. Two patients (4%) discontinued treatment due to toxicity, and there was no treatment-related mortality. Conclusion: RVD-lite is a well-tolerated and highly effective regimen in transplant-ineligible MM with prolonged PFS and OS. This study provides the framework for frailty-adapted triplet and quadruplet regimens in MM patients. This trial was registered at ClinicalTrials.gov (NCT01782963).