Efficacy and Safety Of Melphalan and Prednisone In Combination With Thalidomide, Bortezomib Or Lenalidomide In Newly Diagnosed Transplant-Ineligible Multiple Myeloma Patients: A Single Center Experience

The introduction of new agents has substantially changed the management of patients with multiple myeloma (MM). PATIENTS AND METHODS: We evaluated retrospectively 69 symptomatic newly diagnosed transplant-ineligible MM patients treated at our Institute, between 2004 and 2012, with Melphalan and Prednisone (MP) plus Thalidomide (MPT; 23 patients) or plus Bortezomib (MPV; 30 patients) or plus Lenalidomide (MPR; 16 patients). There were 37 men and 32 woman, median age was 73 years (range 65-84) with 20 patients >75 years, 19 (27.5%) were in stage III according to ISS, 12 (17%) had renal failure (creatinine >1.5 mg/dl at baseline), 7 (10%) an underlying diabetes mellitus and 36 (52%) a cardiovascular disease. Melphalan was given at 9 mg/m² and Prednisone at 60 mg/m² orally on days 1-4; Bortezomib at 1.3 mg/m² intravenously on days 1, 4, 8, 11, 22, 25, 29, 32 for the first 4 cycles and thereafter on days 1, 8, 15, 22; Lenalidomide at 10 mg on days 1-21 and Thalidomide 100 mg/daily were administered orally. All patients received antibacterial prophylaxis; thromboprophylaxis and antiviral prophylaxis were administered to patients treated with IMIDs and Bortezomib, respectively.

To evaluate the safety and efficacy within the MPT-, MPV- and MPR-treated groups.

The overall response rates ( ≥ partial response), according to the IMWG criteria, were 20/23 (87%) in the MPT group, 26/30 (87%) in the MPV group, 11/16 (68%) in the MPR group (including 3, 9, 2 very good partial response and 2, 3, 2 complete response/near complete response, respectively). The median PFS was 29 months (95% CI: 18-NA months) for patients who received MPT, 24 months (95% CI: 20-32 months) with MPV and 21.5 months (95% CI: 17-NA months) with MPR, with no significant differences between the three regimens. Among the 69 patients, the overall grade 3-4 hematologic and non-hematologic toxicities were 36% and 43%, respectively. The most common non-hematologic toxicities included all grades of peripheral neuropathy (14% with MPV, 7.2% with MPT and none with MPR), grade 3-4 infections (7.2% with MPV, 4.3% with MPT and 2.9 with MPR) and grade 3-4 cardiovascular disease (4.3% with MPT, 1.4% with MPV and none with MPR). With the use of thromboprophylaxis in all IMID-treated patients, we observed only one deep vein thrombosis in one patient treated with MPT.

MPT, MPV and MPR are highly active and well tolerated regimens for previously untreated MM patients. The rates of treatment-associated thrombocytopenia and neutropenia were similar between the 3 different regimens and proved transient, predictable and manageable; few patients required supportive care. The results obtained using MP plus one of the recently developed drugs confirm that MPT, MPV and MPR should be considered the standard of care in the frontline treatment of newly diagnosed transplant-ineligible MM patients.

Petrucci:Janssen and Celgene: Honoraria; Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees.