Venetoclax plus LDAC for patients with untreated AML ineligible for intensive chemotherapy

  • Andrew Henry Wei
  • Pau Montesinos
  • Vladimir Ivanov
  • Courtney D DiNardo
  • Jan Novak
  • Kamel Laribi
  • Inho Kim
  • Don Stevens
  • Walter Fiedler
  • Maria Pagoni
  • Olga Samoilova
  • Yu Hu
  • Achilles Anagnostopoulos
  • Julie Bergeron
  • Jing-Zhou Hou
  • Vidhya Murthy
  • Takahiro Yamauchi
  • Andrew Bruce McDonald
  • Brenda Chyla
  • Sathej Gopalakrishnan
  • Qi Jiang
  • Wellington L Mendes
  • John Hayslip
  • Panayiotis Panayiotidis

Beteiligte Einrichtungen

Abstract

BACKGROUND: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy.

METHODS: Adults ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international Phase 3 randomized, double-blind, placebo-controlled trial. Patients (N=211) were randomized 2:1 to either: venetoclax (N=143) or placebo (N=68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1-10. The primary endpoint was overall survival (OS); secondary endpoints included response rates, transfusion independence, and event-free survival.

RESULTS: Median age was 76 years (range 36-93), 38% had secondary AML, and 20% had prior hypomethylating agent (HMA) treatment. The planned primary analysis showed that the venetoclax arm provided a benefit of 25% reduction in the risk-of-death over the LDAC-alone arm (hazard ratio [HR] 0.75 [95% CI 0.52-1.07], p=0.11), although it was not statistically significant; with median OS of 7.2 months and 4.1 months, respectively. An unplanned analysis with an additional 6 months of follow up demonstrated a median OS of 8.4 months for the venetoclax arm (HR 0.70; 95% CI 0.50-0.98; p=0.04). The CR/CRi rates were 48% and 13% for the Venetoclax plus LDAC arm and LDAC-alone arm, respectively. Key grade ≥3 adverse events (Ven vs. LDAC-alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs. 16%), and thrombocytopenia (45% vs 37%).

CONCLUSION: Venetoclax plus LDAC demonstrates a clinically meaningful improvement in remission rates and OS compared to LDAC alone, in the context of a manageable safety profile. These results confirm venetoclax plus LDAC is an important frontline AML treatment option for patients unfit for intensive chemotherapy.

Bibliografische Daten

OriginalspracheEnglisch
ISSN0006-4971
DOIs
StatusVeröffentlicht - 27.03.2020

Anmerkungen des Dekanats

Copyright © 2020 American Society of Hematology.

PubMed 32219442