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 CaraccioloSimona Soverini, Robin Foà, Michele Cavo, Giovanni Martinelli, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Gianantonio Rosti, Gruppo Italiano Malattie Ematologiche dell’Adulto - Chronic Myeloid Leukemia Working Party

Research output: Contribution to journalArticlepeer-review

Abstract

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 ageand 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.

Original languageEnglish
Pages (from-to)1530-1536
Number of pages7
JournalHaematologica
Volume102
Issue number9
DOIs
Publication statusPublished - Aug 31 2017

ASJC Scopus subject areas

  • Hematology

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