A Multicenter, Open Label Study of Oral Lenalidomide and Prednisone (RP) Followed by Oral Lenalidomide Melphalan and Prednisone (MPR) and Oral Lenalidomide Maintenance In Newly Diagnosed Elderly Multiple Myeloma Patients

The combination of Melphalan-Prednisone-Lenalidomide (MPR) has shown promising results in elderly newly diagnosed myeloma patients. In the transplant setting, low-dose chemotherapy (induction) precedes high-dose chemotherapy (autologous transplantation consolidation). This approach reduces tumor mass, with few side effects, before achieving the maximum cyto-reduction with autologous transplantation. The same approach has been designed for the elderly patients. Accordingly induction with lenalidomide plus corticosteroids precedes consolidation with MPR.

A two-stage phase II clinical trial was planned to evaluate the safety and efficacy of Lenalidomide-Prednisone (RP) as induction, followed by Melphalan-Prednisone-Lenalidomide (MPR) as consolidation and Lenalidomide as maintenance in elderly myeloma patients.

Unfit patients with newly diagnosed symptomatic myeloma older than 65 years were enrolled. No exclusion criteria were included in the protocol, to avoid the selection of fit elderly subjects only. Patients with low blood count, abnormal performance status, hepatic, renal, cardiac or pulmonary functions were enrolled. Patients received 4 RP courses (Lenalidomide 25 mg/day for 21 days every 4 weeks, plus Prednisone 50 mg three times/week for 4 weeks) followed by 6 MPR cycles (Melphalan 2 mg and Prednisone 50 mg three times/week, for 4 weeks plus Lenalidomide 10–15 mg/day for 21 days every 4 weeks) and maintenance with Lenalidomide alone (10 mg/day for 21 days every 4 weeks). Two different dose-levels of Lenalidomide were tested in combination with MP: 15 mg (dose-level 1) and 10 mg (dose-level 2). Each cohort included 12 patients, with additional 22 patients enrolled at dose-level 2. Patients were evaluated for efficacy and toxicity after completion of at least 2 MPR cycles.

Forty-six patients (median age 75, range 65–88) were enrolled. Thirty-six patients were evaluable after a median of 7 cycles and a median follow-up of 8.5 months.

During RP induction, the most frequent grade 3–4 hematological adverse events were neutropenia (19%), anemia (11 %), thrombocytopenia (6%). During MPR consolidation, grade 3–4 adverse events were neutropenia (45%), and thrombocytopenia (3%). Neutropenia was increased by the addition of melphalan, but both thrombocytopenia and anemia were reduced. Non-hematological toxicities were more frequent during RP cycles and reduced during MPR cycles (cutaneous rash and infections).

After RP induction, at least partial response (PR) rate was 67%, at least very good partial response (VGPR) was 17%. After 2 MPR cycles, PR rate increase to 72%, including 22% of patients who achieved at least a VGPR.

Induction with RP followed by consolidation with MPR showed a manageable safety profile and reduced the risk of anemia, thrombocytopenia and non-hematological toxicity in unfit elderly myeloma patients. These data will be updated at the meeting.

Palumbo:Celgene Srl: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janseen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide in combination with melphalan for multiple myeloma patients at diagnosis. Guglielmelli:Celgene: Honoraria; Janseen-Cilag: Honoraria. Gay:Celgene: Honoraria. Cavallo:Celgene: Honoraria. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janseen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.