Originally published as JCO Early Release 10.1200/JCO.2007.12.3463 on September 4 2007

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Melphalan, Prednisone, and Lenalidomide Treatment for Newly Diagnosed Myeloma: A Report From the GIMEMA—Italian Multiple Myeloma Network

Antonio Palumbo, Patrizia Falco, Paolo Corradini, Antonietta Falcone, Francesco Di Raimondo, Nicola Giuliani, Claudia Crippa, Giovannino Ciccone, Paola Omedè, Maria Teresa Ambrosini, Francesca Gay, Sara Bringhen, Pellegrino Musto, Robin Foà, Robert Knight, Jerome B. Zeldis, Mario Boccadoro, Maria Teresa Petrucci

From the Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino; Divisione di Ematologia, Istituto Nazionale Tumori, Milano; UO Ematologia e Trapianto di Cellule Staminali, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; Cattedra di Ematologia, Ospedale Ferrarotto, Catania; Cattedra e UO Ematologia e Trapianti midollo, Università degli Studi di Parma, Parma; Sezione Ematologia, Università di Brescia, Spedali Civili, Brescia; Servizio di Epidemiologia dei Tumori dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino, e CPO Piemonte; UO di Ematologia e Trapianto di Cellule Staminali, CROB - Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture; Dipartimento di Biotecnologie e Ematologia, Università La Sapienza, Roma, Italy; and the Celgene Corporation, Summit, NJ

Address reprint requests to Antonio Palumbo, MD, Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Via Genova 3, 10126 Torino, Italy; e-mail: appalumbo{at}yahoo.com

Purpose Lenalidomide has shown significant antimyeloma activity in clinical studies. Oral melphalan, prednisone, and thalidomide have been regarded as the standard of care in elderly multiple myeloma patients. We assessed dosing, efficacy, and safety of melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed elderly myeloma patients.

Patients and Methods Oral melphalan was administered in doses ranging from 0.18 to 0.25 mg/kg on days 1 to 4, prednisone at a 2-mg/kg dose on days 1 to 4, and lenalidomide at doses ranging from 5 to 10 mg on days 1 to 21, every 28 days for nine cycles, followed by maintenance therapy with lenalidomide alone. Aspirin was given as a prophylaxis for thrombosis.

Results Fifty-four patients were enrolled and evaluated after completing the assigned treatment schedule. The maximum tolerated dose was defined as 0.18 mg/kg melphalan and 10 mg lenalidomide. With these doses, 81% of patients achieved at least a partial response, 47.6% achieved a very good partial response, and 23.8% achieved a complete immunofixation-negative response. In all patients, 1-year event-free and overall survival rates were 92% and 100%, respectively. At the maximum tolerated dose, grade 3 adverse events included neutropenia (38.1%), thrombocytopenia (14.2%), febrile neutropenia (9.5%), vasculitis (9.5%), and thromboembolism (4.8%); grade 4 adverse events were neutropenia (14.2%) and thrombocytopenia (9.5%).

Conclusion Oral MPR therapy is a promising first-line treatment for elderly myeloma patients. Hematologic adverse events were frequent but manageable. A low incidence of nonhematologic adverse events was noted. Aspirin appears to provide adequate antithrombosis prophylaxis.

published online ahead of print at www.jco.org on September 4, 2007.

Sponsored by the Università degli Studi di Torino, Italy, and supported in part by research funding from Celgene Corporation (Summit, NJ; to M.B.) and by Fondazione Neoplasie Sangue Onlus, Associazione Italiana Leucemie, Compagnia di S. Paolo, Associazione per lo Studio e la Cura delle Malattie del Sangue, Fondazione Cassa di Risparmio di Torino, Ministero Università Ricerca Scientifica e Tecnologia (MIUR), and Consiglio Nazionale delle Ricerche (CNR).

Presented in part in abstract format at European Hematology Association, Amsterdam, the Netherlands, June 15-18, 2006; American Society of Clinical Oncology, Atlanta, GA, June 4-6, 2006; American Society of Hematology, Atlanta, GA, December 10-13, 2005; and the American Society of Hematology, Orlando, FL, December 9-12, 2006.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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