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Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy

Steven Coutre, Michael Choi, Richard R. Furman, Herbert Eradat, Leonard Heffner, Jeffrey A. Jones, Brenda Chyla, Lang Zhou, Suresh Agarwal, Tina Waskiewicz, Maria Verdugo, Rod A. Humerickhouse, Jalaja Potluri, William G. Wierda and Matthew S. Davids

Key points

  • ORR was 67% with venetoclax for 36 patients with CLL refractory to or who relapsed after idelalisib; median PFS has not yet been reached

  • Common adverse events included mild gastrointestinal events and grade 3/4 cytopenias and no patients experienced tumor lysis syndrome

Abstract

B-cell receptor pathway inhibitors (BCRi) have transformed treatment for chronic lymphocytic leukemia (CLL); however, efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRi is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi prior to enrollment. Venetoclax was initiated at 20mg daily followed by intra-patient ramp up to 400mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib, with ORR of 67% (24/36); two patients achieved complete remission and one had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached and estimated 12-month PFS was 79%. The most common AEs (all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. Trial registration: clinicaltrials.gov #NCT02141282.

  • Submitted June 2, 2017.
  • Accepted December 15, 2017.