A phase II trial to evaluate the combination of bendamustine (Treanda) with bortezomib (Velcade) and dexamethasone in patients with relapsed/refractory multiple myeloma “showed a remarkable response rate of 60.9%,” and when minor responses were included, 75.9%,” researchers reported in Blood. “The short time to response (31 days) and to best response (111 days) is clinically relevant, because rapid tumor control usually corresponds with fast improvement of clinical symptoms,” the investigators noted.
The 79 study patients were enrolled at nine participating centers in Austria and the Czech Republic. The patients’ median age was 64. Most had stage I (34.2%) or stage II disease (39.2%).The median number of prior treatment lines was two.
Treatment consisted of bendamustine at 70 mg/m2 on days 1 and 4, bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 intravenously, and dexamethasone at 20 mg on days 1, 4, 8, and 11. Cycles were repeated every 4 weeks until a maximum of eight cycles. In patients with no response, treatment was discontinued at cycle 4, the investigators explained.
Key Data
Complete response occurred in 12 patients, very good partial response in 16 patients, and partial response in 20 patients, yielding the overall response rate of 60.9%. Adding the minor responses in 12 patients resulted in the overall response rate of 75.9%. The overall response rate was similar in patients who had been previously exposed to bortezomib, lenalidomide (Revlimid), and to both bortezomib and lenalidomide.
The overall response rate was lower for patients with adverse cytogenetic features than for those without such aberrations, as defined by fluorescence in situ hybridization (53% vs 67%). Progression-free survival was 9.7 months and overall survival was 25.6 months, and these endpoints did not differ significantly according to adverse cytogenetic features. “Multivariate analysis showed high LDH, ≥ 3 prior treatment lines, and low platelet counts correlating with short survival,” the investigators noted.
The treatment regimen was relatively well tolerated, although grade 3/4 hematologic toxicities were seen in up to one-third of patients, the authors noted. Grade 3–5 infections were noted in 23% of patients, two of whom had fatal outcomes. “Hence, G-CSF [Neupogen] prophylaxis should be considered particularly in elderly frail patients. Herpes zoster prophylaxis is mandatory but clinical virus reactivation may occur even during adequate prophylaxis,” the authors commented.
Grade ≤ 2 polyneuropathy increased with duration of therapy, from 19% at baseline to 52% at cycle 8. Other nonhematologic side effects, mostly grade 1/2, included insomnia/fatigue, nausea, emesis, and constipation. ■
Ludwig H, et al: Blood. November 13, 2013 (early release online).
