Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.
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Chatzikonstantinou Thomas, Scarfò Lydia, Karakatsoulis Georgios, Minga Eva, Chamou Dimitra, Iacoboni Gloria, Kotaskova Jana, Demosthenous Christos, Smolej Lukas, Mulligan Stephen, Alcoceba Miguel, Al-Shemari Salem, Aurran-Schleinitz Thérèse, Bacchiarri Francesca, Bellido Mar, Bijou Fontanet, Calleja Anne, Medina Angeles, Khan Mehreen Ali, Cassin Ramona, Chatzileontiadou Sofia, Collado Rosa, Christian Amy, Davis Zadie, Dimou Maria, Donaldson David, Santos Gimena Dos, Dreta Barbara, Efstathopoulou Maria, El-Ashwah Shaimaa, Enrico Alicia, Fresa Alberto, Galimberti Sara, Galitzia Andrea, García-Serra Rocío, Gimeno Eva, González-Gascón-Y-Marín Isabel, Gozzetti Alessandro, Guarente Valerio, Guieze Romain, Gogia Ajay, Gupta Ritu, Harrop Sean, Hatzimichael Eleftheria, Herishanu Yair, Hernández-Rivas José-Ángel, Inchiappa Luca, Jaksic Ozren, Janssen Susanne, Kalicińska Elżbieta, Laribi Kamel, Karakus Volkan, Kater Arnon P, Kho Bonnie, Kislova Maria, Konstantinou Eliana, Koren-Michowitz Maya, Kotsianidis Ioannis, Kreitman Robert J, Labrador Jorge, Lad Deepesh, Levin Mark-David, Levy Ilana, Longval Thomas, Lopez-Garcia Alberto, Marquet Juan, Martin-Rodríguez Lucia, Maynadié Marc, Maslejova Stanislava, Mayor-Bastida Carlota, Mihaljevic Biljana, Milosevic Ivana, Miras Fatima, Moia Riccardo, Morawska Marta, Murru Roberta, Nath Uttam Kumar, Navarro-Bailón Almudena, Oliveira Ana C, Olivieri Jacopo, Oscier David, Panovska-Stavridis Irina, Papaioannou Maria, Papajík Tomas, Kubova Zuzana, Phumphukhieo Punyarat, Pierie Cheyenne, Puiggros Anna, Rani Lata, Reda Gianluigi, Rigolin Gian Matteo, Ruchlemer Rosa, Daniel de Deus Santos Marcos, Schipani Mattia, Schiwitza Annett, Shen Yandong, Simkovic Martin, Smirnova Svetlana, Abdelrahman Soliman Dina Sameh, Spacek Martin, Tadmor Tamar, Tomic Kristina, Tse Eric, Vassilakopoulos Theodoros, Visentin Andrea, Vitale Candida, von Tresckow Julia, Vrachiolias George, Vukovic Vojin, Walewska Renata, Wasik-Szczepanek Ewa, Xu Zhenshu, Yagci Munci, Yañez Lucrecia, Yassin Mohamed, Zuchnicka Jana, Angelopoulou Maria, Antic Darko, Biderman Bella, Catherwood Mark, Claus Rainer, Coscia Marta, Cuneo Antonio, Demirkan Fatih, Espinet Blanca, Gaidano Gianluca, Kalashnikova Olga B, Laurenti Luca, Nikitin Eugene, Pangalis Gerassimos A, Panagiotidis Panagiotis, Popov Viola Maria, Pospisilova Sarka, Sportoletti Paolo, Stavroyianni Niki, Tam Constantine, Trentin Livio, Chatzidimitriou Anastasia, Bosch Francesc, Doubek Michael, Ghia Paolo, Stamatopoulos Kostas
Аннотация
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.