Incidence of second primary malignancies and related mortality in patients with imatinib-treated chronic myeloid leukemia
Gabriele Gugliotta,
Fausto Castagnetti,
Massimo Breccia,
Francesco Albano,
Alessandra Iurlo,
Tamara Intermesoli,
Elisabetta Abruzzese,
Luciano Levato,
Mariella D’Adda,
Patrizia Pregno,
Francesco Cavazzini,
Fabio Stagno,
Bruno Martino,
Gaetano La Barba,
Federica Sorà,
Mario Tiribelli,
Catia Bigazzi,
Gianni Binotto,
Massimiliano Bonifacio,
Clementina Caracciolo,
Simona Soverini,
Robin Foà,
Michele Cavo,
Giovanni Martinelli,
Fabrizio Pane,
Giuseppe Saglio,
Michele Baccarani,
Gianantonio Rosti
Affiliations
Gabriele Gugliotta
Institute of Hematology “L. and A. Seràgnoli”, “S. Orsola-Malpighi” University Hospital, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
Fausto Castagnetti
Institute of Hematology “L. and A. Seràgnoli”, “S. Orsola-Malpighi” University Hospital, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
Massimo Breccia
Division of Cellular Biotechnologies and Hematology, University Sapienza, Rome, Italy
Hematology Unit, Azienda Ospedaliera “Papa Giovanni XXIII”, Bergamo, Italy
Elisabetta Abruzzese
Hematology Unit, “S. Eugenio” Hospital, Rome, Italy
Luciano Levato
Hematology Unit, “Pugliese-Ciaccio” Hospital, Catanzaro, Italy
Mariella D’Adda
Hematology Unit, Azienda Ospedaliera “Spedali Civili”, Brescia, Italy
Patrizia Pregno
Hematology Unit, Azienda Ospedaliero Universitaria “Città della Salute e della Scienza”, Torino, Italy
Francesco Cavazzini
Chair of Hematology, Azienda Ospedaliero Universitaria Arcispedale “S. Anna”, University of Ferrara, Italy
Fabio Stagno
Chair and Division of Hematology, Azienda Ospedaliero Universitaria Policlinico – V. Emanuele, University of Catania, Italy
Bruno Martino
Hematology Unit, Azienda Ospedaliera “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy
Gaetano La Barba
Department of Hematology, “Spirito Santo” Hospital, Pescara, Italy
Federica Sorà
Chair of Hematology, “Cattolica del Sacro Cuore” University, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
Mario Tiribelli
Division of Hematology and Bone Marrow Transplantation, Azienda Sanitaria Universitaria Integrata di Udine, Italy
Catia Bigazzi
Hematology Unit, “C. e G. Mazzoni” Hospital, Ascoli Piceno, Italy
Gianni Binotto
Hematology Unit, Azienda Ospedaliera di Padova, University of Padova, Italy
Massimiliano Bonifacio
Department of Medicine, Section of Hematology, University of Verona, Italy
Clementina Caracciolo
Hematology Unit, “P. Giaccone” Hospital, Palermo, Italy
Simona Soverini
Institute of Hematology “L. and A. Seràgnoli”, “S. Orsola-Malpighi” University Hospital, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
Robin Foà
Division of Cellular Biotechnologies and Hematology, University Sapienza, Rome, Italy
Michele Cavo
Institute of Hematology “L. and A. Seràgnoli”, “S. Orsola-Malpighi” University Hospital, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
Giovanni Martinelli
Institute of Hematology “L. and A. Seràgnoli”, “S. Orsola-Malpighi” University Hospital, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
Fabrizio Pane
Department of Biochemistry and Medical Biotechnologies, “Federico II” University, Napoli, Italy
Giuseppe Saglio
Chair of Hematology, Department of Clinical and Biological Sciences, “S Luigi Gonzaga” University Hospital, University of Torino, Orbassano, Italy
Michele Baccarani
Department of Hematology and Oncology “L. and A. Seràgnoli”, University of Bologna, Italy
Gianantonio Rosti
Institute of Hematology “L. and A. Seràgnoli”, “S. Orsola-Malpighi” University Hospital, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials in which imatinib was given as first-line treatment. We then compared the observed incidence and mortality with those expected in the age- and sex-matched Italian general population, calculating standardized incidence and standardized mortality ratios. After a median follow-up of 74 months, 5.8% patients developed second primary malignancies. The median time from chronic myeloid leukemia to diagnosis of the second primary malignancies was 34 months. We did not find a higher incidence of second primary malignancies compared to that in the age- and sex-matched Italian general population, with standardized incidence ratios of 1.06 (95% CI: 0.57–1.54) and 1.61 (95% CI: 0.92–2.31) in males and females, respectively. Overall, 3.1% patients died of second primary malignancies. The death rate in patients with second primary malignancies was 53% (median overall survival: 18 months). Among females, the observed cancer-related mortality was superior to that expected in the age- and sex-matched Italian population, with a standardized mortality ratio of 2.41 (95% CI: 1.26 – 3.56). In conclusion, our analysis of patients with imatinib-treated chronic myeloid leukemia did not reveal a higher incidence of second primary malignancies; however, the outcome of second primary malignancies in such patients was worse than expected. Clinicaltrials.gov: NCT00514488, NCT00510926.