Bortezomib As Induction Before Autologous Transplantation, Followed by Lenalidomide As Consolidation-Maintenance in Untreated Multiple Myeloma Patients Antonio Palumbo, Francesca Gay, Patrizia Falco, Claudia Crippa, Vittorio Montefusco, Francesca Patriarca, Fausto Rossini, Simona Caltagirone, Giulia Benevolo, Norbert Pescosta, Tommasina Guglielmelli, Sara Bringhen, Massimo Offidani, Nicola Giuliani, Maria Teresa Petrucci, Pellegrino Musto, Anna Marina Liberati, Giuseppe Rossi, Paolo Corradini, and Mario Boccadoro From the Divisione di Ematologia dell’Universita ` di Torino and Unita ` di Ematologia, Azienda Ospedaliero- Universitaria San Giovanni Battista di Torino, Torino; Sezione Ematologia, Universita ` di Brescia, Spedali Civili, Bres- cia; Divisione di Ematologia, Istituto Nazionale Tumori, Milano; Clinica Emato- logica, Universita ` di Udine, Udine; Emato- logia, Ospedale San Gerardo, Monza; Unitá di Ematologia, Azienda Ospedaliero- Universitaria San Giovanni Battista di Torino, Torino; Divisione di Ematologia, Ospedale Centrale, Bolzano; Diparti- mento di Scienze Cliniche e Biologiche, Azienda Ospedaliera San Luigi Gonzaga, Orbassano; Clinica di Ematologia, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona, Ancona; Cattedra di Ematologia and Centro Trapianti Midolleo Osseo, Universita ` Degli Studi di Parma, Parma; Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita ` La Sapienza, Roma; Unita ` di Ematologia e Trapianto di Cellule Staminali, Centro di Riferimento Oncologico di Basilicata, Rionero in Vulture, Potenza; and Clinica Medica I, Policlinico Monteluce, Perugia, Italy. Submitted March 2, 2009; accepted September 9, 2009; published online ahead of print at www.jco.org on January 4, 2010. Supported by Fondazione Neoplasie Sangue Onlus, Associazione per lo Studio e la Cura delle Malattie del Sangue, Regione Piemonte, Ministero Universita ` Ricerca Scientifica e Tecnologia, and Consiglio Nazionale delle Ricerche. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: Antonio Palumbo, MD, Divisione di Ematologia dell’Universita ` di Torino, Azienda Ospedaliero-Universitaria San Giovanni Battista, Via Genova 3, 10126 Torino, Italy; e-mail: appalumbo@yahoo.com. © 2010 by American Society of Clinical Oncology 0732-183X/10/2899-1/$20.00 DOI: 10.1200/JCO.2009.22.7561 A B S T R A C T Purpose To evaluate the effect of bortezomib as induction therapy before autologous transplantation, followed by lenalidomide as consolidation-maintenance in myeloma patients. Patients and Methods Newly diagnosed patients age 65 to 75 years were eligible. Induction (bortezomib, doxorubicin, and dexamethasone [PAD]) included four 21-day cycles of bortezomib (1.3 mg/m 2 on days 1, 4, 8, and 11), pegylated liposomal doxorubicin (30 mg/m 2 on day 4), and dexamethasone (40 mg/d; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4). Autologous transplantation was tandem melphalan 100 mg/m 2 (MEL100) and stem-cell support. Consolidation included four 28-day cycles of lenalidomide (25 mg/d on days 1 to 21 every 28 days) plus prednisone (50 mg every other day), followed by maintenance with lenalidomide (LP-L; 10 mg/d on days 1 to 21) until relapse. Primary end points were safety (incidence of grade 3 to 4 adverse events [AEs]) and efficacy (response rate). Results A total of 102 patients were enrolled. In a per-protocol analysis, after PAD, 58% of patients had very good partial response (VGPR) or better, including 13% with complete response (CR); after MEL100, 82% of patients had at least VGPR and 38% had CR; and after LP-L, 86% of patients had at least VGPR and 66% had CR. After median follow-up time of 21 months, the 2-year progression-free survival rate was 69%, and the 2-year overall survival rate was 86%. During induction, treatment-related mortality was 3%; grade 3 to 4 AEs included thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%). During consolidation- maintenance, grade 3 to 4 AEs were neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). Conclusion Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance, is an effective regimen. J Clin Oncol 28. © 2010 by American Society of Clinical Oncology INTRODUCTION Multiple myeloma (MM) is the second most com- mon hematologic malignancy worldwide. Annu- ally, in the United States and Europe, it causes nearly 11,000 and 19,000 deaths, respectively. 1,2 The introduction of new drugs, such as thalido- mide, bortezomib, and lenalidomide, has signifi- cantly improved overall response rates (ORRs), progression-free survival (PFS), and overall sur- vival (OS). Patients who received these new drugs had longer survival from relapse compared with patients who did not receive these new therapies (30.9 v 14.8 months, respectively; P  .001). Simi- larly, patients diagnosed in the past decade had a 50% improvement in OS compared with patients diagnosed before December 1996, when thalido- mide was introduced (44.8 v 29.9 months, respec- tively; P  .001). 3 The proteasome inhibitor bortezomib is an ac- tive agent in MM patients. 4 In a randomized study, bortezomib plus dexamethasone was compared JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T © 2010 by American Society of Clinical Oncology 1 http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2009.22.7561 The latest version is at Published Ahead of Print on January 4, 2010 as 10.1200/JCO.2009.22.7561 Copyright 2010 by American Society of Clinical Oncology Copyright © 2010 by the American Society of Clinical Oncology. All rights reserved. January 22, 2010 from 130.192.107.102. Information downloaded from jco.ascopubs.org and provided by Universita Studi Di Torino - Biblioteca Polo Clinico on