J Clin Oncol 31, 2013 (suppl; abstr 8517)
Antonio Palumbo, Sara Bringhen, Vincent Rajkumar, Giulia Lupparelli, Saad Zafar Usmani, Anders Waage, Alessandra Larocca, Bronno van der Holt, Pellegrino Musto, Andrea Evangelista, Sonja Zweegman, Meletios A. Dimopoulos, Roman Hajek, Michele Cavo, Sagar Lonial, Giovannino Ciccone, Mario Boccadoro, Bart Barlogie, Pieter Sonneveld, Philip L. McCarthy; Division of Hematology, University of Turin, Turin, Italy; Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy; Mayo Clinic, Rochester, MN; Myeloma Institute for Research and Therapy, Little Rock, AR; St. Olav's Hospital/NTNU, Trondheim, Norway; Erasmus MC, Rotterdam, Netherlands; Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy; Cancer Epidemiology Unit, CeRMS and CPO Piemonte, Città della Salute e della Scienza, University of Torino, Torino, Italy; VU University Medical Center, Amsterdam, Netherlands; Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece; School of Medicine, University of Ostrava; Institute of clinical haematology, University Hospital Ostrava, Ostrava, Czech Republic; Bologna University School of Medicine, Seràgnoli Institute of Hematology, Bologna, Italy; Emory University School of Medicine, Atlanta, GA; Roswell Park Cancer Institute, Buffalo, NY
Background: An increased risk of SPM in MM pts treated with len has been reported. We performed an IPD metanalysis to estimate the incidence of SPM according to len exposure.
Methods: Randomized studies of MM, from PubMed and ASCO/IMW/ASH (after 2000), that met the following criteria, were included: randomization to treatment with len (len-trials); randomization to treatment including new drug but not len (no-len-trials); available SPM data. Primary aim was to estimate cumulative incidence of SPMs by len exposure, corrected for death (competing event).
Results: Data from 6,383 pts (3,218 from 8 len-trials, 3,165 from 10 no-len-trials) were analyzed. Median age was 69 years. During follow-up (median=30 mos) 420 (6.6%) SPMs were reported: 188 (2.9%) hematologic and 232 (3.6%) solid cancers. Solid tumors occurred with similar incidence in all groups. Incidence of hematologic SPM was significantly higher in patients receiving len (3.2 vs 1.1, p=0.04), but risk is limited to patients treated with melphalan+len (4.1, 95%CI: 2.4-5.8) with no excess in other combinations (len without melphalan: 1.2, 0.0-2.6; melphalan without len: 1.1, 0.0-2.7) (p=0.003). The cumulative incidence of death for any cause was much higher than the risk of SPM.
Conclusions: The risk of hematologic SPMs was higher in pts receiving melphalan+len. The benefit/risk profile of len treatment remains positive. Cumulative incidence (%) of SPMs and death (95%CI).