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Real-world outcomes following venetoclax therapy in patients with chronic lymphocytic leukemia or Richter syndrome: a FILO study of the French compassionate use cohort


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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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.


The study was supported by AbbVie.

Author information




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.

Corresponding author

Correspondence to Romain Guièze.

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Conflict of interest

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.

Ethics approval

The study was approved by the board of the FILO and was conducted according to the Declaration of Helsinki.

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All the authors approved the final manuscript.

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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).

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  • Chronic lymphocytic leukemia
  • Richter syndrome
  • B cell
  • Targeted therapy
  • Bcl-2 inhibitor
  • Venetoclax