Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Chatzikonstantinou, T.; Scarfo, 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, M. A.; Cassin, R.; Chatzileontiadou, S.; Collado, R.; Christian, A.; Davis, Z.; Dimou, M.; Donaldson, D.; Santos, G. D.; Dreta, B.; Efstathopoulou, M.; El-Ashwah, S.; Enrico, A.; Fresa, A.; Galimberti, S.; Galitzia, A.; Garcia-Serra, R.; Gimeno, E.; Gonzalez-Gascon-y-Marin, I.; Gozzetti, A.; Guarente, V.; Guieze, R.; Gogia, A.; Gupta, R.; Harrop, S.; Hatzimichael, E.; Herishanu, Y.; Hernandez-Rivas, J. -A.; Inchiappa, L.; Jaksic, O.; Janssen, S.; Kalicinska, E.; Kamel, L.; Karakus, V.; Kater, A. P.; Kho, B.; Kislova, M.; Konstantinou, E.; Koren-Michowitz, M.; Kotsianidis, I.; Kreitman, R. J.; Labrador, J.; Lad, D.; Levin, M. -D.; Levy, I.; Longval, T.; Lopez-Garcia, A.; Marquet, J.; Martin-Rodriguez, L.; Maynadie, M.; Maslejova, S.; Mayor-Bastida, C.; Mihaljevic, B.; Milosevic, I.; Miras, F.; Moia, R.; Morawska, M.; Murru, R.; Nath, U. K.; Navarro-Bailon, A.; Oliveira, A. C.; Olivieri, J.; Oscier, D.; Panovska-Stavridis, I.; Papaioannou, M.; Papajik, T.; Kubova, Z.; Phumphukhieo, P.; Pierie, C.; Puiggros, A.; Rani, L.; Reda, G.; Rigolin, G. M.; Ruchlemer, R.; Daniel de Deus Santos, M.; Schipani, M.; Schiwitza, A.; Shen, Y.; Simkovic, M.; Smirnova, S.; Abdelrahman Soliman, D. S.; 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.; Yanez, 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, O. B.; Laurenti, L.; Nikitin, E.; Pangalis, G. A.; Panagiotidis, P.; Popov, V. M.; Pospisilova, S.; Sportoletti, P.; Stavroyianni, N.; Tam, C.; Trentin, L.; Chatzidimitriou, A.; Bosch, F.; Doubek, M.; Ghia, P.; Stamatopoulos, K.

doi:10.1016/j.eclinm.2023.102307

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/ EFPIA Innovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY / Chatzikonstantinou, T.; Scarfo, 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, M. A.; Cassin, R.; Chatzileontiadou, S.; Collado, R.; Christian, A.; Davis, Z.; Dimou, M.; Donaldson, D.; Santos, G. D.; Dreta, B.; Efstathopoulou, M.; El-Ashwah, S.; Enrico, A.; Fresa, A.; Galimberti, S.; Galitzia, A.; Garcia-Serra, R.; Gimeno, E.; Gonzalez-Gascon-y-Marin, I.; Gozzetti, A.; Guarente, V.; Guieze, R.; Gogia, A.; Gupta, R.; Harrop, S.; Hatzimichael, E.; Herishanu, Y.; Hernandez-Rivas, J. -A.; Inchiappa, L.; Jaksic, O.; Janssen, S.; Kalicinska, E.; Kamel, L.; Karakus, V.; Kater, A. P.; Kho, B.; Kislova, M.; Konstantinou, E.; Koren-Michowitz, M.; Kotsianidis, I.; Kreitman, R. J.; Labrador, J.; Lad, D.; Levin, M. -D.; Levy, I.; Longval, T.; Lopez-Garcia, A.; Marquet, J.; Martin-Rodriguez, L.; Maynadie, M.; Maslejova, S.; Mayor-Bastida, C.; Mihaljevic, B.; Milosevic, I.; Miras, F.; Moia, R.; Morawska, M.; Murru, R.; Nath, U. K.; Navarro-Bailon, A.; Oliveira, A. C.; Olivieri, J.; Oscier, D.; Panovska-Stavridis, I.; Papaioannou, M.; Papajik, T.; Kubova, Z.; Phumphukhieo, P.; Pierie, C.; Puiggros, A.; Rani, L.; Reda, G.; Rigolin, G. M.; Ruchlemer, R.; Daniel de Deus Santos, M.; Schipani, M.; Schiwitza, A.; Shen, Y.; Simkovic, M.; Smirnova, S.; Abdelrahman Soliman, D. S.; 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.; Yanez, 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, O. B.; Laurenti, L.; Nikitin, E.; Pangalis, G. A.; Panagiotidis, P.; Popov, V. M.; Pospisilova, S.; Sportoletti, P.; Stavroyianni, N.; Tam, C.; Trentin, L.; Chatzidimitriou, A.; Bosch, F.; Doubek, M.; Ghia, P.; Stamatopoulos, K.. - In: ECLINICALMEDICINE. - ISSN 2589-5370. - 65:(2023). [10.1016/j.eclinm.2023.102307]