ORLANDO, Fla.—Bendamustine, prednisolone, and lenalidomide (RBP) was well tolerated in patients with relapsed or refractory multiple myeloma in whom maximum tolerated dose (MTD) had not been reached, results of a phase 1 feasibility and safety study have shown.

To date, patients have tolerated a dose of lenalidomide 20 mg (days 1-21) and bendamustine 60 mg/m² (days 1-2), and further increases in doses per protocol are in progress, according to Wolfram Pönisch, of the University Clinical Center, Leipzig, Germany, and colleagues.

While the role of lenalidomide monotherapy in the treatment of relapsed/refractory patients with multiple myeloma is established, combination therapies with lenalidomide are still under investigation, the investigators noted in a poster presentation during the 52nd American Society of Hematology Annual Meeting and Exposition. Bendamustine, a bifunctional alkylating agent with a purine-like benzimidazole ring, has been shown to be effective in combination with steroids, thalidomide, and bortezomib for the treatment of patients with multiple myeloma.

In this study, the first cohort of patients received a starting dose of lenalidomide 10 mg/day (days 1-21), bendamustine 60 mg/m²/day (days 1-2), and prednisolone 100 mg/day (days 1-4). Escalation steps in the next cohorts were lenalidomide to 15, 20, and 25 mg, followed by an escalation step of bendamustine to 75 mg/m². Three patients were enrolled at each dose level, and the first 2 cycles were evaluated for MTD. To evaluate efficacy, patients received RBP in 4-week cycles for a maximum of 8 cycles. Patients with stable or responding disease following 8 cycles of RBP received single-agent oral lenalidomide 10 mg once daily (days 1-21 q28d) as maintenance.

To date, 12 patients were enrolled, 10 of which completed at least 2 cycles and were hence evaluable (3 at each dose level of 10, 15, or 20 mg lenalidomide and 1 at 25 mg lenalidomide). Response was assessed using modified European Group for Blood and Marrow Transplantation (EBMT) criteria to include near-complete remission (nCR) and very good partial remission (VGPR). Ten of 12 patients have responded: 1 VGPR, 1 nCR, 6 partial remissions, 2 minor remissions; 2 had stable disease. None developed dose-limiting hematoxicity, defined as an ANC <1.0 x 109/L with fever for >3 days or an ANC <0.5 x 109/L for >7 days or platelet count <25 x 109/L for >3 days. Four patients had neutropenia (CTC grade ≥3), but no thrombocytopenia (common toxicity criteria grade ≥3) was observed. No grade 3 or 4 nonhematologic toxicity was encountered and no dose modification was required.