MM-494 Chemo or Chemo-Free Regimens in Heavily Pretreated Multiple Myeloma? Role of Bendamustine-Bortezomib-Dexamethasone (BVD) in Novel Agents' Era

Context: Bendamustine is a bi-functional alkylating agent which has proven to be effective in relapsed/refractory and in newly diagnosed multiple myeloma (MM). Objective: Aiming to provide further insights in this field, and the novel agents' era, we present a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD) Design: 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), refractory to all drugs previously received (also bortezomib), received BVD (B 90 mg/sqm days 1, 2; V 1.3 mg/sqm days 1, 4, 8, 11, D 20 mg days 1, 2, 4, 5, 8, 9, 11, 12, pegfilgrastim day +4) every 28 days, until progression. Setting and Patients: All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. Results: Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no hospitalization was required, no septic shock was observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second autoSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e., carfilzomib, daratumumab and pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of bendamustine was 9.6 months (r.2-36). Conclusions: BVD has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to SCT, also after failure of novel agents.