VRd versus VCd as induction therapy for newly diagnosed multiple myeloma: A Phase III, randomized study

Abstract

Three-drug based induction regimens are a current standard of care for autologous stem-cell transplantation (ASCT)-eligible, newly diagnosed, multiple myeloma (MM) patients (pts). Bortezomib, lenalidomide and dexamethsone (VRd), bortezomib, cyclophosphamide and dexamethasone (VCd) and bortezomib, thalidomide and dexamethasone (VTd) are commonly used triplets. We conducted a randomized trial to compare VRd versus VCd for induction in patients with newly diagnosed multiple myeloma. Overall 125 patients (median age years (range, to ) were randomly assigned to receive receive 4 cycles of VRd (n=65) or VCd (n=60). Patients received Inj Bortezomib 1.3 mg/m2 subcutaneously weekly x 16 weeks, Tab dexamethsone 40 mg per week, and cap lenalidomide 15 mg daily day 1-15 every 28 days OR cyclophosphamide 300 mg/m2 day1,8 and 15, (total dose was calculated and given orally over 22 days every 28 days. All patients received acyclovir and septran prophylaxis. Patients were monitored on monthly basis for toxicity and response was evaluated at the end of 4 cycles as per IMWG criteria. Patients median age was 58 years (range, 31 to 70), 73(58.4%) were males. Patients characteristics were similar in both groups as regards to ISS stage (ISS III –VRd : 43.1%,VCd : 38%), high risk cytogenetics (VRd -12.1% vs VCd-11.1%), BM plasma cells %, and extramedullary disease. On intention to treat analysis – after 4 cycles – 61.5% of patients in VRd arm achieved ≥VGPR compared to 48.3% in VCd arm, p 0.09 (primary end point). CR rates were superior in the VRD arm; 35.4 % (sCR-9.2%) vs 18.3% (sCR-5%), p< 0.02. Hematologic toxicity and peripheral neuropathy was not significantly different in 2 arms. This study is registered with clinical trials registry ( REF/2016/08/012008). Triplet induction therapy VRd was superior as regards to response rates for the VRd arm.