Abstract
The BCL2 inhibitor venetoclax is transforming the management of patients with chronic lymphocytic leukemia (CLL), given its high efficacy in relapsed/refractory CLL as observed in both early-phase and randomized clinical trials. The present study aimed to determine whether venetoclax is effective and well tolerated in patients with CLL or Richter’s syndrome (RS) in a real-world setting and to highlight factors impacting survival. Data from a venetoclax French compassionate use program were collected for 67 patients (60 with CLL and 7 with RS). Most patients presented adverse genetic features, such as TP53 disruption (74%) or complex karyotype (58%). Tumor lysis syndrome was observed in 14 (22%) patients, and 16 (24%) patients were hospitalized for grade III/IV infection. In the CLL cohort, ORR was 75 %, 1-year PFS was 61% (95% CI = 47–72%) and 1-year OS 70% (95% CI = 56–80%). No impact of TP53 disruption was noted while complex karyotype was identified as a predictor of both inferior PFS (HR = 3.46; 95% CI = 1–12; log-rank p = 0.03) and OS (HR = 3.2; 95% CI = 0.9–11.4, log-rank p = 0.047). Among the seven patients with RS, two achieved an objective response to venetoclax; however, the median OS was only 1.1 month. The well-balanced safety/efficacy profile of venetoclax is confirmed in this real-world setting. Complex karyotype should be evaluated as a predictive factor of survival for patients treated by venetoclax.
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Acknowledgments
The authors would thank all participating physicians who treated the patients as part of the venetoclax French compassionate program and for providing the clinical data required. Editorial assistance, in the form of language editing and correction, was provided by XpertScientific Editing and Consulting Services.
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The study was supported by AbbVie.
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F.B. and R.G. designed the study, analyzed the data, and wrote the manuscript. B.P. performed statistical analyses. F.B. collected clinical data. L.V. helped to interpret cytogenetic data. A.C., M-S.D., S.A., F.C., C.H., S.D.G., D.R-W, B.H., T.A., J.D., A.B., E.T., K.L., N.D., P.M., A-S.M., C.D., F.N-K., A.D., P.F., and L.Y. included patients and collected clinical and biological data. All authors approved the final manuscript.
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Bouclet Florian: AbbVie, Amgen
Herbaux Charles: research funding: Takeda, AbbVie; honoraria and non-financial support: Roche, Janssen-Cilag, AbbVie, Takeda
de Guibert Sophie: honoraria: AbbVie, Janssen, Gilead
Hivert Bénedicte: participation boards scientifiques: Sanofi, Janssen
Aurran Thérèse: honoraria: Janssen, AbbVie
Dupuis Jehan: Celgene and AbbVie
Laribi Kamel: scientific partnership: Novartis, Takeda, Janssen, Sandoz, AbbVie, Amgen, Roche
Michallet Anne-Sophie: scientific partnership: Janssen AbbVie
Dartigeas Caroline: honoraria and travels support: AbbVie, Roche. Travel support: Janssen
Tournilhac Olivier: Roche Gilead Amgen AbbVie Takeda Sandoz
Delmer Alain: advisory board: Janssen, Astra Zeneca, Roche, AbbVie. Travel support: Janssen, AbbVie, Roche, Gilead
Feugier Pierre: Janssen, Roche, Gilead, Amgen, AstraZeneca, AbbVie
Ysebaert Loic: advisory boards: AbbVie, Astra Zeneca, Gilead, Janssen, Roche
Guieze Romain: advisory board: Astra Zeneca, Janssen, AbbVie. Travel support: Roche, AbbVie, Gilead, Jansen
There is no conflict of interest to disclose for the remaining authors.
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The study was approved by the board of the FILO and was conducted according to the Declaration of Helsinki.
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Bouclet, F., Calleja, A., Dilhuydy, MS. et al. Real-world outcomes following venetoclax therapy in patients with chronic lymphocytic leukemia or Richter syndrome: a FILO study of the French compassionate use cohort. Ann Hematol 100, 987–993 (2021). https://doi.org/10.1007/s00277-021-04419-w
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DOI: https://doi.org/10.1007/s00277-021-04419-w