Secondary malignancies and survival of FCR‐treated patients with chronic lymphocytic leukemia in Central Europe

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 2; pp. 1961 - 1971
• Main Authors: Kósa, Fruzsina, Nečasová, Tereza, Špaček, Martin, Giannopoulos, Krzysztof, Hus, Iwona, Jurková, Tereza, Koriťáková, Eva, Chrápavá, Marika, Nováčková, Martina, Katinová, Ivana, Krejčí, Denisa, Jujka, Adam, Mátrai, Zoltán, Vályi‐Nagy, István, Robak, Tadeusz, Doubek, Michael
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-01-2023; John Wiley and Sons Inc; Wiley
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Cancer; Chemotherapy; Chronic lymphocytic leukemia; CLL population; Codes; Cyclophosphamide - therapeutic use; Data collection; Decision making; Diagnosis; Disease-Free Survival; Drugs; Europe - epidemiology; FCR therapy; Hospitals; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - epidemiology; Lymphoma; Male; Malignancy; Medical prognosis; Melanoma; Patients; Registration; Retrospective Studies; Risk factors; Rituximab - therapeutic use; secondary malignancy; Statistical analysis; Survival; Tumors; Europe; Poland; Czech Republic; Hungary; Central Europe; secondary malignancy; CLL population; FCR therapy; survival
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5033

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.
We analyzed 25,814 newly diagnosed CLL patients from Czechia, Hungary, and Poland between 2004 and 2016. The probability to develop a secondary malignancy within 4 years from starting the first‐line FCR therapy ranged between 28.0% and 36.8% with age at diagnosis, male gender, any malignancy prior to the CLL diagnosis, and the CLL treatment to be the key risk factors. 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 indicating that when evaluating new therapies in regulatory and reimbursement decision making, the factor of secondary malignancies deserves deeper considerations.