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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  • dc.contributor.author Chatzikonstantinou, Thomas
  • dc.contributor.author Gimeno Vázquez, Eva
  • dc.contributor.author Puiggros Metje, Anna Maria
  • dc.contributor.author Espinet Solà, Blanca
  • dc.contributor.author Stamatopoulos, Kostas
  • dc.date.accessioned 2024-10-11T06:19:40Z
  • dc.date.available 2024-10-11T06:19:40Z
  • dc.date.issued 2023
  • dc.description.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.
  • dc.description.sponsorship This project was supported in part by AbbVie; EU/EFPIA Innovative Medicines Initiative [2] Joint Undertaking HARMONY grant n° 116026; the Hellenic Precision Medicine Network in Oncology; MH-CZ_AZV_NU23-03-00401; MH CZ DRO (FNBr, 65269705); MH CZ DRO (FNOl, 00098892), program COOPERATIO (research area ONCO), and NPO-NUVR LX22NPO5102. Munci Yagci was provided with study materials.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Chatzikonstantinou T, Scarfò L, Karakatsoulis G, Minga E, Chamou D, Iacoboni G, et al. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY. EClinicalMedicine. 2023 Nov 15;65:102307. DOI: 10.1016/j.eclinm.2023.102307
  • dc.identifier.doi http://dx.doi.org/10.1016/j.eclinm.2023.102307
  • dc.identifier.issn 2589-5370
  • dc.identifier.uri http://hdl.handle.net/10230/61375
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof EClinicalMedicine. 2023 Nov 15;65:102307
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/116026
  • dc.rights © 2023 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Chronic lymphocytic leukemia
  • dc.subject.keyword Other cancers
  • dc.subject.keyword Other malignancies
  • dc.subject.keyword Second primary malignancies
  • dc.title Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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