Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY
Author(s)
Chatzikonstantinou, T; Scarfò, L; Karakatsoulis, G; Minga, E; Chamou, D; Iacoboni, G; Kotaskova, J; Demosthenous, C; Smolej, L; Mulligan, S; Alcoceba, M; Al-Shemari, S; Aurran-Schleinitz, T; Bacchiarri, F; Bellido, M; Bijou, F; Calleja, A; Medina, A; Khan, MA; Cassin, R; Chatzileontiadou, S; Collado, R; Christian, A; Davis, Z; Dimou, M; Donaldson, D; Dos Santos, G; Dreta, B; Efstathopoulou, M; El-Ashwah, S; Enrico, A; Fresa, A; Galimberti, S; Galitzia, A; García-Serra, R; Gimeno, E; González-Gascón-y-Marín, I; Gozzetti, A; Guarente, V; Guieze, R; Gogia, A; Gupta, R; Harrop, S; Hatzimichael, E; Herishanu, Y; Hernández-Rivas, JÁ; Inchiappa, L; Jaksic, O; Janssen, S; Kalicińska, E; Kamel, L; Karakus, V; Kater, AP; Kho, B; Kislova, M; Konstantinou, E; Koren-Michowitz, M; Kotsianidis, I; Kreitman, RJ; Labrador, J; Lad, D; Levin, MD; Levy, I; Longval, T; Lopez-Garcia, A; Marquet, J; Martin-Rodríguez, L; Maynadié, M; Maslejova, S; Mayor-Bastida, C; Mihaljevic, B; Milosevic, I; Miras, F; Moia, R; Morawska, M; Murru, R; Nath, UK; Navarro-Bailón, A; Oliveira, AC; Olivieri, J; Oscier, D; Panovska-Stavridis, I; Papaioannou, M; Papajík, T; Kubova, Z; Phumphukhieo, P; Pierie, C; Puiggros, A; Rani, L; Reda, G; Rigolin, GM; Ruchlemer, R; de Deus Santos, MD; Schipani, M; Schiwitza, A; Shen, Y; Simkovic, M; Smirnova, S; Soliman, DSA; Spacek, M; Tadmor, T; Tomic, K; Tse, E; Vassilakopoulos, T; Visentin, A; Vitale, C; von Tresckow, J; Vrachiolias, G; Vukovic, V; Walewska, R; Wasik-Szczepanek, E; Xu, Z; Yagci, M; Yañez, L; Yassin, M; Zuchnicka, J; Angelopoulou, M; Antic, D; Biderman, B; Catherwood, M; Claus, R; Coscia, M; Cuneo, A; Demirkan, F; Espinet, B; Gaidano, G; Kalashnikova, OB; Laurenti, L; Nikitin, E; Pangalis, GA; Panagiotidis, P; Popov, VM; Pospisilova, S; Sportoletti, P; Stavroyianni, N; Tam, C; Trentin, L; Chatzidimitriou, A; Bosch, F; Doubek, M; Ghia, P; Stamatopoulos, K;
Journal Title
eClinicalMedicine
Publication Type
Research article
Abstract
BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. METHODS: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. FINDINGS: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). INTERPRETATION: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. FUNDING: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.
Publisher
Elsevier
Keywords
Chronic lymphocytic leukemia; Other cancers; Other malignancies; Second primary malignancies
Department(s)
Clinical Haematology
Open Access at Publisher's Site
https://doi.org/10.1016/j.eclinm.2023.102307
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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