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Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study.

Publication ,  Journal Article
Wei, AH; Strickland, SA; Hou, J-Z; Fiedler, W; Lin, TL; Walter, RB; Enjeti, A; Tiong, IS; Savona, M; Lee, S; Chyla, B; Popovic, R; Salem, AH ...
Published in: J Clin Oncol
May 20, 2019

PURPOSE: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML. PATIENTS AND METHODS: Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS). RESULTS: Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months). CONCLUSION: Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

May 20, 2019

Volume

37

Issue

15

Start / End Page

1277 / 1284

Location

United States

Related Subject Headings

  • Sulfonamides
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Humans
  • Female
  • Cytarabine
  • Bridged Bicyclo Compounds, Heterocyclic
 

Citation

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Wei, A. H., Strickland, S. A., Hou, J.-Z., Fiedler, W., Lin, T. L., Walter, R. B., … Roboz, G. J. (2019). Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol, 37(15), 1277–1284. https://doi.org/10.1200/JCO.18.01600
Wei, Andrew H., Stephen A. Strickland, Jing-Zhou Hou, Walter Fiedler, Tara L. Lin, Roland B. Walter, Anoop Enjeti, et al. “Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study.J Clin Oncol 37, no. 15 (May 20, 2019): 1277–84. https://doi.org/10.1200/JCO.18.01600.
Wei AH, Strickland SA, Hou J-Z, Fiedler W, Lin TL, Walter RB, et al. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol. 2019 May 20;37(15):1277–84.
Wei, Andrew H., et al. “Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study.J Clin Oncol, vol. 37, no. 15, May 2019, pp. 1277–84. Pubmed, doi:10.1200/JCO.18.01600.
Wei AH, Strickland SA, Hou J-Z, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong W-J, Hayslip J, Roboz GJ. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol. 2019 May 20;37(15):1277–1284.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

May 20, 2019

Volume

37

Issue

15

Start / End Page

1277 / 1284

Location

United States

Related Subject Headings

  • Sulfonamides
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Humans
  • Female
  • Cytarabine
  • Bridged Bicyclo Compounds, Heterocyclic