EClinicalMedicine (Nov 2023)

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

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

Journal volume & issue
Vol. 65
p. 102307

Abstract

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Summary: 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.

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