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Incidence of Secondary Malignancies in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Era of Tyrosine Kinase Inhibitors (TKI)

Koji Sasaki, Hagop M. Kantarjian, Susan M. O'Brien, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, Guillermo Garcia-Manero, William G Wierda, Naval Daver, Alessandra Ferrajoli, Koichi Takahashi, Preetesh Jain, Mary B. Rios, Sherry Pierce, Elias J. Jabbour and Jorge E. Cortes

Abstract

Introduction

With TKI therapy the survival of patients with CML-CP is approaching to that of general population. Data on the incidence of secondary malignancies in CML is conflicting given the rarity of CML and the low incidence of secondary malignancies. The aim of this study is to evaluate the incidence of secondary malignancies in patients with CML-CP in a large US-based database.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database identified 13,276 patients with newly diagnosed CML-CP during the period from 2001 to 2014. Patients who had prior history of cancer, concurrent diagnosis of other malignancies at the same diagnostic year, and patients who developed secondary leukemia after the diagnosis of CML were excluded. Cumulative incidence of secondary malignancies were estimated with the presence of competing risk of death. Standard incidence ratio (SIR) was calculated from person-years at risk divided by expected cases based on the age-adjusted incidence ratio of the 2000 U.S. standard population.

Results

Of 13,276 patients, secondary malignancies were observed in 597 patients (4%) with a median follow-up of 69 months (Table 1). The three most common secondary malignancies were male genital system 130 (22%), digestive system 124 (21%) and respiratory system, 92 (15%). The 5-year and 10-year cumulative incidence of death for all patients was 30.5% (95% confidence interval [CI], 29.6-31.4), and 41.8% (95% CI, 40.7-43.0). The 5-year and 10-year cumulative incidence of secondary malignancies were 4.4% (95% CI, 4.0-4.8), and 7.2% (95% CI, 6.6-7.9), respectively (Figure 1). Overall SIR was 1.204 (95% CI, 1.108-1.301). The increased SIRs were observed in male genital system of 1.593 (95% CI, 1.319-1.866); digestive system, 1.291 (95% CI, 1.064-1.519); skin, 1.588 (95% CI, 1.083-2.093); urinary system, 1.366 (95% CI, 1.008-1.724); and miscellaneous, 1.877 (1.033-2.721) (Figure 2). The decreased SIR was observed in breast cancer of 0.665 (95% CI, 0.479-0.852). Overall excess absolute risk was 1.714 per 1,000 person years at risk (95% CI, 0.622-2.805).

Conclusion

Relative incidence of overall secondary malignancies in CML-CP is slightly higher than that of general population with minimal increase in the excess absolute risk. Given the limitation of registry data, the uncertainty of use and type of TKI, and response status at the diagnosis of secondary malignancies, conclusions regarding actual risk should be cautiously interpreted. It is also at this stage not possible to determine whether any possible increased risk is associated with the diagnosis of CML-CP per se or the use of TKIs. Further analysis is needed.

Disclosures Kantarjian: Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; ARIAD: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; Delta-Fly Pharma: Research Funding. O'Brien: Amgen: Consultancy; Alexion: Consultancy; Celgene: Consultancy; Astellas: Consultancy; Janssen: Consultancy; Vaniam Group LLC: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy, Other: Research Support: Honorarium, Research Funding; GSK: Consultancy; Acerta: Other: Research Support: Honorarium, Research Funding; Gilead Sciences, Inc.: Consultancy, Other: Research Support: Honorarium, Research Funding; Regeneron: Other: Research Support: Honorarium, Research Funding; Aptose Biosciences, Inc.: Consultancy; ProNAI: Other: Research Support: Honorarium, Research Funding; Pharmacyclics: Consultancy, Other: Research Support: Honorarium, Research Funding; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy. Wierda: Emergent: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Karyopharm: Research Funding; The University of Texas MD Anderson Cancer Center: Employment; Acerta: Research Funding; Kite: Research Funding; GSK/Novartis: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Juno: Research Funding; Genentech/Roche: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding. Daver: Daiichi-Sankyo: Research Funding; Kiromic: Research Funding; Incyte Corporation: Honoraria, Research Funding; Jazz: Consultancy; Bristol-Myers Squibb Company: Consultancy, Research Funding; Otsuka America Pharmaceutical, Inc.: Consultancy; Karyopharm: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Immunogen: Research Funding; Pfizer Inc.: Consultancy, Research Funding; Sunesis Pharmaceuticals, Inc.: Consultancy, Research Funding. Takahashi: Symbio Pharmaceuticals: Consultancy. Jabbour: Bristol-Myers Squibb: Consultancy. Cortes: Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Sun Pharma: Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding; ImmunoGen: Consultancy, Research Funding; ARIAD: Consultancy, Research Funding.

  • * Asterisk with author names denotes non-ASH members.