1. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.
- Author
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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, Santos GD, 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, Laribi K, 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, Daniel de Deus Santos M, Schipani M, Schiwitza A, Shen Y, Simkovic M, Smirnova S, Abdelrahman Soliman DS, 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, and Stamatopoulos K
- 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., Competing Interests: TC received honoraria from AbbVie. LS received consulting fees from AbbVie, BeiGene, AstraZeneca, Lilly, and Janssen, honoraria from Janssen and Octapharma, support for attending meetings from BeiGene and Janssen and advisory board fees from Merck. SMu received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche and BeiGene. JAHR received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. LI received honoraria from AbbVie, Roche, and Janssen-Cilag. APK received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, Roche/Genentech, support for attending meetings from Janssen and AbbVie. M-DL received travel expenses from Janssen and AbbVie. GMR received honoraria for participation to speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. JVT received consulting fees from AbbVie, AstraZeneca, BeiGene, and Janssen, honoraria for scientific talks from AbbVie, AstraZeneca, BeiGene, Janssen, Lilly, and Roche, travel support from AbbVie, AstraZeneca, BeiGene, Janssen, Roche, and Lilly, and advisory boards fees for AbbVie, Amgen, AstraZeneca, BeiGene. GI received honoraria from Novartis, BMS, Sandoz, AstraZeneca, Janssen, Kite/Gilead, and Miltenyi, support for attending meetings from Kite/Gilead, AstraZeneca, and AbbVie and advisory board fees from Kite/Gilead, Novartis, BMS, and Autolus. FBi received support for attending meetings from AbbVie. RCo received support for attending meetings from Janssen-Cilag and S.A. SG received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. RGS received support for attending meetings from AbbVie and S.L.U. RG received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, AstraZeneca. YH received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. OJ received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. LK received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. MKM received honoraria from Novartis, Pfizer, and Gad Medical LTD and support for attending meetings from Novartis. IKo received honoraria and consulting fees from AbbVie and Janssen. IM received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. ANB received honoraria, advisory board fees and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. JO received honoraria from AbbVie, AstraZeneca, and Janssen. GR received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. TP received honoraria and advisory board fees from AbbVie, Janssen-Cilag, and AstraZeneca and support for attending meeting from AstraZeneca. MS received honoraria and support for attending meeting from AstraZeneca, AbbVie, and Janssen-Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. MSp received honoraria and consulting and advisory board fees, and support for attending meeting from AbbVie, AstraZeneca, and Janssen. ET received support for attending meetings from Takeda. TV received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. CV received honoraria from AbbVie, consulting fees from AstraZeneca and support for attending meeting from AstraZeneca, Takeda, and Janssen. RW received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. EWS received honoraria from AbbVie, Roche, and Janssen-Cilag and support for attending meetings from AbbVie. LY received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. MAn received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. MC received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. ACu received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. FD support for attending meetings from Janssen and AbbVie. GG received honoraria, and advisory board fees from AbbVie, AstraZeneca, Beigene, Janssen and advisory board fees from Lilly. EN received honoraria from AbbVie. LSm received consulting fees, honoraria and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. NS received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. CT received honoraria from AbbVie, Beigene, Janssen, and LOXO. FB received consulting fees, honoraria and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. MDo received honoraria and advisory board fees from AbbVie, AstraZeneca and Janssen, advisory board fees from Swixx, and support for attending meetings from Janssen. PG received honoraria and consulting fees from AbbVie, AstraZeneca, BMS, Janssen, Lilly/Loxo Oncology, MSD, and Roche; grant support from AbbVie, AstraZeneca, BMS, Janssen. KS received honoraria from Janssen, AbbVie, Lilly and AstraZeneca, consulting fees and support for attending meetings from Janssen and AstraZeneca. GK, EM, DC, JK, CD, MA, SA, TAS, FBa, MB, ACa, AM, AKM, RC, SC, ACh, ZD, MDi, DD, GDS, BD, ME, SEA, AE, AF, AG, EG, IGGM, AGo, AjG, RGu, SH, EH, SJ, EKa, VK, BK, MK, EK, RJK, JL, DL, IL, TL, ALG, JM, LMR, MMa, SM, CMB, BM, FM, RM, MMo, RMu, UKN, ACO, DO, IPS, MP, ZK, PP, CP, AP, LR, RR, MDDS, AS, YS, MSi, SS, DSAS, TT, KT, AV, GV, VV, ZX, MYa, MY, JZ, DA, BB, MCa, RCl, BE, OBK, LL, GP, PPa, VMP, SP, PS, LT, AC, have no conflict of interest to disclose., (© 2023 Published by Elsevier Ltd.)
- Published
- 2023
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