This is the first large-scale cross-country analysis of patients with chronic lymphocytic leukemia (CLL) aimed to evaluate the incidence, types, and key prognostic factors of secondary malignancies, and to assess the impact on overall survival based on retrospective claims data from three Central European countries. We analyzed 25,814 newly diagnosed CLL patients from Czechia, Hungary, and Poland; 10,312 (39.9%) patients were treated for CLL in study periods between 2004 and 2016. Out of the treated patients, 1986 (19.3%) received the FCR therapy in the first line and 779 (7.6%) received FCR in subsequent lines. We observed that 33.7% of treated patients developed secondary malignancies during the study. Based on country estimates, the probability to develop a secondary malignancy within 4 years since starting the first-line FCR therapy ranged between 28.0% and 36.8%. We found the age at diagnosis, male gender, any malignancy prior to the CLL diagnosis, and the CLL treatment to be the key risk factors for developing secondary malignancies. Specifically, the FCR therapy was a statistically significant (p < 0.001) prognostic factor for risk increase with the hazard ratio between 1.46 and 1.60. Across the three Central European countries, we observed consistent results indicating FCR increased the risk of secondary malignancies in CLL patients. We conclude that secondary malignancies are clearly an undervalued burden for CLL patients, caregivers, and the healthcare system. When evaluating new therapies in regulatory and reimbursement decision making, the factor of secondary malignancies deserves deeper considerations.

1st Department of Internal Medicine Haematology United St István and St László Hospital Budapest Hungary

Department of Hematology Medical University of Lodz Lodz Poland

Experimental Hematooncology Department Medical University of Lublin Lublin Poland

General University Hospital Prague Prague Czech Republic

Institute of Biostatics and Analysis Ltd Brno Czech Republic

Institute of Biostatistics and Analyses of the Faculty of Medicine Brno Czech Republic

Instutute of Hematology and Transfusion Medicine Warsaw Poland

Janssen Cilag Polska Warsaw Poland

Janssen Global Services LLC Budapest Hungary

Medical University of Lublin Department of Clinical Transplantology Medical University of Lublin Lublin Poland

University Hospital Brno and CEITEC Masaryk University Brno Czech Republic

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