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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; no patients experienced tumor lysis syndrome.

Publisher's Note: There is a Blood Commentary on this article in this issue.

Abstract

B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis 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 before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (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. This trial was registered at www.clinicaltrials.gov as #NCT02141282.

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