Oral Revlimid^R Plus Melphalan and Prednisone (R-MP) for Newly Diagnosed Multiple Myeloma.

Introduction. Lenalidomide (Revlimid^R) is a novel, orally active immunomodulatory drug effective for the treatment of refractory myeloma. In this multicenter trial, we evaluate the potential additive and synergistic effect of the combination Revlimid^R, melphalan and prednisone (R-MP).

Materials and Methods. Patients (pts) with newly diagnosed symptomatic multiple myeloma older than 65 years were treated with 9 courses of Revlimid^R (5–10 mg/day for 21days every 4–6 weeks) plus MP (melphalan 0.18–0.25 mg/kg and prednisone 2 mg/kg for 4 days every 4–6 weeks). The trial was designed to define the toxicity profile of R-MP and to analyze the efficacy of this combination. Four different dose levels were tested: 1. melphalan 0.18 mg/kg + Revlimid^R 5 mg/day; 2. melphalan 0.25 mg/kg + Revlimid^R 5 mg/day; 3. melphalan 0.18 mg/kg + Revlimid^R 10 mg/day; 4. melphalan 0.25 mg/kg + Revlimid^R 10 mg/day. Each cohort included 6 pts. Dose limiting toxicity (DLT) was defined as: any grade ≥ 3 non-hematologic toxicity; grade 4 neutropenia lasting >7 days; any other grade 4 hematologic toxicity and any treatment delay due to toxicity that occurred during the first cycle. All pts received ciprofloxacin and aspirin as prophylaxis.

Results. At present, 24 pts (median age 72, range 61–77) received at least one R-MP course and were evaluated. No DLTs were observed in the first 2 dose levels; 1 DLT was observed with melphalan 0.18 mg/Kg and Revlimid^R mg/kg (grade 4 neutropenia lasting> 7 days); 2 DLTs were reached with melphalan 0.25 and Revlimid^R 10 mg (1 neutropenic fever, 1 grade 3 cutaneous toxicity). After 1 cycle of R-MP, no one was in complete remission (according to the EBMT/IBMTR criteria), 2 pts (9.5%) showed a myeloma protein reduction of 75–99%, 7 pts (28.6%) a response of 50–74%, and 15 (61.9%) a response of <50% (1 of these pts showed a 30% reduction in the size of soft tissue plasmacytomas), no disease progressions were observed. After 3 cycles of R-MP, myeloma protein reduction of 75–99% was detected in 1 patients (11,1%), response of 50–74% in 8 patients (55.6%) and response <50% in 5 patients (33.3%), no disease progressions were observed. Grade 3 or 4 adverse events were reported in 9 patients (35%). They included: 1 thrombo-embolism (4.2%); 5 grade 4 neutropenias (20.9%) ;4 grade 3 neutropenias (16.7%); 4 grade 3 thrombocytopenias (16.7%); 1 febrile neutropenia (4.2%); 2 grade 3 dermatological toxicities (8.3%); 1 grade 3 metabolic toxicity (4.2%) and 1grade 4 metabolic toxicity (4.2%). One pt discontinued Revlimid^R because of grade 3 dermatological toxicity. Dose- reduction was required in 4 pts (1 grade 4 neutropenia >7 days, 1 treatment delay due to toxicity, 2 grade 3 dermatological toxicities).

Conclusions. R-MP was well tolerated with a manageable toxicity. Significant response rate was observed. It represents a feasible and promising approach for newly diagnosed pts who are not candidates for transplant. Fifteen additional pts were treated with the fix dose of melphalan 0.18 mg/kg + Revlimid^R 10 mg/day, results are too premature to assess efficacy. An update of these data will be presented.