Outcome of Patients Receiving Venetoclax for Chronic Lymphocytic Leukemia (CLL) in Real-Life Clinical Practice: Results of the French ATU Program on Behalf of the Filo Group

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.5549-5549
• Main Authors: Bouclet, Florian, Calleja, Anne, Dilhuydy, Marie-Sarah, Amorim, Sandy, Cymbalista, Florence, Herbaux, Charles, de Guibert, Sophie, Roos-Weil, Damien, Hivert, Benedicte, Aurran, Thérèse, Dupuis, Jehan, Blouet, Anaise, Tchernonog, Emmanuelle, Laribi, Kamel, Dmytruk, Natalia, Morel, Pierre, Michallet, Anne-Sophie, Dartigeas, Caroline, Farnault, Laure, Lavaud, Anne, Plantier, Isabelle, Bay, Jacques-Olivier, Tournilhac, Olivier, Delmer, Alain Jacques, Feugier, Pierre, Ysebaert, Loic, Guieze, Romain
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-118622

Introduction.The BCL-2 inhibitor venetoclax has demonstrated high efficiency in relapsed/refractory (R/R) CLL patients with an overall response rate (ORR) of 79%, regardless of the TP53gene status. Venetoclax has then been EMEA-approved for CLL patients with TP53disruption who are unsuitable for or have failed a BCR inhibitor (BCRi) and those without TP53 inactivation who have failed both immunochemotherapy and a BCRi. Whether this agent provides a well-balanced safety/efficacy profile and a prolonged survival in real-world practice remains to be investigated. Methods. An early access program (ATU) of venetoclax was available in France between July 22thand December 4th, 2016 for R/R CLL patients as per EMEA label. We retrospectively analyzed the outcome of patients included in this program who had received at least one day of venetoclax. Data quality was ensured using on-site data verification and computerized discrepancy errors. Results. Data concerning both clinical features andoutcome were available for 72 of the 93 patients for whom venetoclax was requested in this program. Among them, only 63 patients received at least one day of venetoclax for progressive CLL or Richter syndrome (RS) and were included in the present analysis. Median age was 69 years (range, 25-89) and sex ratioM/F was 47/16. A total of 56 patients received venetoclax for CLL and 7 for RS. Patients had previously received a median of 4 prior therapeutic lines (range, 0-7) including FCR in 43 (68%) of them, BTK inhibitor (BTKi) in 46 (73%) and PI3Kδ inhibitor (PI3Kδi) in 21 (33%); 5 had prior autologous stem cell transplantation (SCT) and 4 allogeneic SCT. At time of treatment with venetoclax, 32 (76%) patients carried TP53disruption (data available for 42 patients) and 19 (61%) had complex karyotype (CK) defined as ≥ 3 abnormalities (data available for 31 patients). IGHV mutational status was available for 26 patients. Treatment was administered as per label recommandations with a 5-week ramp up phase until the target dosage of 400 mg per day. Median follow-up was 17 months. Median time on therapy was 11.9 months (range, 0.1-24.6). Among adverse events of interest, tumor lysis syndrome (TLS) was observed in 19% of case, most of them being biological TLS and 3% were clinical TLS, and 15 (24%) patients developed infections requiring hospitalization. Autoimmune cytopenia was seen in 9.5% of patients. Four (7%) patients developed RS while on venetoclax for progressive CLL. To date, a tota