Lenolidamide (Revlimid), in Combination with Cyclophosphamide and Dexamethasone (CRD) Is an Effective Regimen for Heavily Pre-Treated Myeloma Patients.

Lenolidamide (Revlimid®) is an oral immunomodulatory drug that has been shown to be effective for the treatment of relapsed refractory myeloma, and in-vitro laboratory studies suggest that its action may be synergistic with a number of conventional chemotherapeutic agents. The aim of this study is to assess the efficacy and toxicity profile when lenolidamide is used in combination with cyclophosphamide and dexamethasone for patients with relapsed refractory disease. Multiply relapsed patients were given Revlimid 25mg po on days 1–21, dexamethasone 40mg po days 1–4 and days 12–15, and cyclophosphamide 500 mg po days 1, 8, 15 and 21 of a 28 day cycle for a maximum of 6 cycles of treatment. Prophylaxis with acyclovir, septrin and proton pump inhibitors was routinely used, 1 high risk patient received prophylactic anticoagulation. Toxicity profiles and response were assessed every 4 weeks. To date 18 patients have been included in the study with median age of 60.5 years (range 34–76). All were heavily pre-treated with a median of 4 previous lines of therapies (range 2–8). 12 patients had received high dose melphalan, 18 patients thalidomide and 16 patients bortezomib. One case had undergone an allogeneic BMT. The median time from diagnosis to treatment initiation was 55.5 months (range 11–122). To date 81 complete courses of therapy have been given to 18 patients with median number of 5 courses (range 1–6). 8 patients experienced neutropenia with the neutophil count falling below 0.5×10⁹/L in a total number of 14 cycles, which resulted in a dose reduction or stopping of cyclophosphamide in 8 patients. 12 patients received GCSF to maintain their neutrophil count. 5 patients required dose reduction/omit of Revlimid. 4 patients required intravenous antibiotics for neutropenic fever. The side effect profile was manageable, importantly no patient experienced sedation, constipation or worsening of peripheral neuropathy. 2 patients with a heavy myeloma load suffered a DVT, but continued on therapy achieving a PR once anti-coagulation had been commenced. 14 of the 17 patients assessable for response achieved a response with 1 CR, 3 VGPR, 8 PR and 2 MR according to EBMT criteria. The median time to response was prompt at 32 days (range 21–68). To date only 2 patients have discontinued therapy because of a failure to respond to therapy and 1 stopped due to liver toxicity. 13 patients have completed treatment and 5 still remain on treatment. The combination of CRD is effective in heavily pretreated myeloma patients and has a manageable toxicity profile. In view of the neutropenia further studies using this combination are currently being investigated using cyclophosphamide on days 1 and 8 only.