Velcade/Revlimid. The safety and efficacy of Velcade in combination with Revlimid® (lenalidomide, Celgene) in the treatment of relapsed and relapsed/refractory myeloma has been evaluated in a Phase I trial at the Dana-Farber Cancer Institute. The rationale for this combination is that preclinical studies have shown that in patient myeloma cells that are resistant to Velcade, Revlimid can restore sensitivity and the combination has a synergistic effect.

Patients with relapsed or refractory myeloma who had received at least one prior therapy were eligible for the study, whose primary objectives were to evaluate the safety of the combination and determine the maximum tolerated dose (MTD) and recommended dose for future study.

Patients received daily Velcade (1.0 or 1.3 mg/m² on days 1, 4, 8, and 11 of each 21-day cycle) in combination with Revlimid (5-20 mg) for a maximum of 8 cycles, with an extension phase for responding patients. Dexamethasone could be added if patients experienced progressive disease. A total of 8 cohorts (one for each dose combination) of 3 to 6 patients each were enrolled, with an additional 10 patients at the MTD.

Encouraging preliminary results were presented at the 2005 Annual Meeting of the American Society of Hematology (ASH). (Richardson et al. Blood. 2005;106(11). Abstract #365.) Of the 21 evaluable patients, 67% had achieved a response (1 complete response [CR], 1 near CR, 9 partial responses [PR], and 3 minor responses). These patients were heavily pretreated, with a median of 4 lines of previous therapy, which in some cases, included either Velcade or Revlimid.

At the time of the meeting, no dose-limited toxicity (DLT) had been reported in the first 3 cohorts (up to 10 mg Revlimid and 1.0 mg/m² Velcade). One DLT (low serum sodium level, Grade 3 in severity) was reported in cohort 4 (10 mg Revlimid and 1.3 mg/m² Velcade) and one DLT (a secondary shingles infection that delayed treatment) was reported in cohort 6 (up to 15 mg Revlimid and 1.3 mg/m² Velcade). Dose reductions of Velcade only (n=6) or both Velcade and Revlimid (n=3) were undertaken beyond the second cycle due to low white blood cell or platelet counts but there were no discontinuations of treatment. The maximum tolerated dose had not yet been reached. Phase II trials of this regimen are planned both in relapsed and/or refractory disease and in newly diagnosed myeloma.