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Bendamustine is a bifunctional alkylating agent, with low toxicity, that produces both single- and double-strand breaks in DNA, and shows incomplete cross resistance with other alkylating drugs, proved to be effective either in relapsed or refractory and in new diagnosed MM as single agent or combined with steroid and has also additive/synergistic activity with bortezomib.

Here we evaluate the efficacy and tolerance of bendamustine in combination with bortezomib-dexamethasone in patients with relapsed and refractory multiple myeloma, whose prognosis is severe, so that there is a strong need for new options for the management of these patients. A retrospective analysis of patients with relapsed and refractory MM, who had received bendamustine as salvage therapy, has been performed.

39 patients, 21 males, 18 females, with advanced multiple myeloma, treated with several lines of treatments, and refractory to all the lines previously performed, received a schedule Bendamustine-based. Median age at diagnosis was 57 years (r.36-82) while age at start of treatment was 62 years (r.37-83), and median number of prior lines of treatment was 6 (r.2-11). ISS was equally distributed, and cytogenetic characteristics were evaluable in 9 patients, only two of whom had cytogenetic abnormalities, and in particular one of them had del13q and in the other one was observed t(11;14). All the patients had previously been treated with schedule containing bortezomib and lenalidomide, while 90% of them had been treated with melphalan, 77% with cyclophosphamide and 34% with anthracyclines, and 30% had also received radiotherapy. 58% of patients had undergone at least to a single autologous stem cell transplantation. Last treatment before bendamustine was a bortezomib-based regimen in 39%, an IMIDs- based regimen in 49% (a combined bortezomib/IMIDs-based regimen in 27%), while 12% of patients had received other chemotherapies. All patients were relapsed and refractory to last therapies received.

Only patients completing at least two courses of Bendamustine were considered for analysis. A total of 128 cycles was administered (median 3, range 2-9). Bendamustine was variously associated to bortezomib (66%), or IMIDs (25%) and only in 9% it was combined only with dexametasone. In our schedule, Bendamustine was given, at a median dose of 90 mg/sqm (range total dose : 120-180) on day +1 and +2 every 28 days. Median OS from diagnosis was 56.5 months (range 6-145), while median OS from start of Bendamustine was 6.5 months (range 2-30). 16/39 patients went in progressive disease during treatment, 2/39 patients died for other causes (one for cardiovascular disease and the other one had a gastric cancer). Grade 3 transfusion-dependent anemia occurred in 31% while in 46% grade 3 neutropenia occurred. No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs.

According to IMWG response criteria, after a median follow up of 6 months (r.2-30), 1 patient achieved a complete response, 1 patient achieved a VGPR and 21 out of 39 evaluable patients achieved a partial response after a median time of 2 months with an overall response rate of 59% and 12 patient were considered in stable disease, which can be considered an impressive result in this subset of patients. In particular, for 4 patients of this study, Bendamustine treatment was, after having achieved a PR, a bridge to second autologous stem cell transplantation, and for one patient a bridge to allogenic stem cell transplantation.