Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia

Courtney D. DiNardo; Curtis A. Lachowiez; Koichi Takahashi; Sanam Loghavi; Lianchun Xiao; Tapan M. Kadia; Naval Daver; Maria Adeoti; Nicholas J. Short; Koji Sasaki; Sa Wang; Gautam Borthakur; Ghayas C. Issa; Abhishek Maiti; Yesid Alvarado; Naveen Pemmaraju; Guillermo Montalban‐Bravo; Lucia Masárová; Musa Yılmaz; Nitin Jain; Michael Andreeff; Elias Jabbour; Guillermo Garcia‐Manero; Steven M. Kornblau; Farhad Ravandi; Marina Konopleva; Hagop M. Kantarjian

doi:10.1200/jco.20.03736

Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia

Courtney D. DiNardo(The University of Texas MD Anderson Cancer Center), Curtis A. Lachowiez(The University of Texas MD Anderson Cancer Center), Koichi Takahashi(The University of Texas MD Anderson Cancer Center), Sanam Loghavi(The University of Texas MD Anderson Cancer Center), Lianchun Xiao(The University of Texas MD Anderson Cancer Center), Tapan M. Kadia(The University of Texas MD Anderson Cancer Center), Naval Daver(The University of Texas MD Anderson Cancer Center), Maria Adeoti(The University of Texas MD Anderson Cancer Center), Nicholas J. Short(The University of Texas MD Anderson Cancer Center), Koji Sasaki(The University of Texas MD Anderson Cancer Center), Sa Wang(The University of Texas MD Anderson Cancer Center), Gautam Borthakur(The University of Texas MD Anderson Cancer Center), Ghayas C. Issa(The University of Texas MD Anderson Cancer Center), Abhishek Maiti(The University of Texas MD Anderson Cancer Center), Yesid Alvarado(The University of Texas MD Anderson Cancer Center), Naveen Pemmaraju(The University of Texas MD Anderson Cancer Center), Guillermo Montalban‐Bravo(The University of Texas MD Anderson Cancer Center), Lucia Masárová(The University of Texas MD Anderson Cancer Center), Musa Yılmaz(The University of Texas MD Anderson Cancer Center), Nitin Jain(The University of Texas MD Anderson Cancer Center), Michael Andreeff(The University of Texas MD Anderson Cancer Center), Elias Jabbour(The University of Texas MD Anderson Cancer Center), Guillermo Garcia‐Manero(The University of Texas MD Anderson Cancer Center), Steven M. Kornblau(The University of Texas MD Anderson Cancer Center), Farhad Ravandi(The University of Texas MD Anderson Cancer Center), Marina Konopleva(The University of Texas MD Anderson Cancer Center), Hagop M. Kantarjian(The University of Texas MD Anderson Cancer Center)

Journal of Clinical Oncology

May 27, 2021

10.1200/jco.20.03736

Cited by 329Open Access

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Abstract

PURPOSE: Sixty percent of newly diagnosed patients with acute myeloid leukemia (ND-AML) receiving frontline therapy attain a complete response (CR), yet 30%-40% of patients relapse. Relapsed or refractory AML (R/R-AML) remains a particularly adverse population necessitating improved therapeutic options. This phase Ib/II study evaluated the safety and efficacy of fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin combined with the B-cell lymphoma-2 inhibitor venetoclax in ND-AML and R/R-AML. MATERIALS AND METHODS: The phase IB portion (PIB) enrolled patients with R/R-AML using a 3 + 3 dose escalation and de-escalation algorithm for identification of maximum tolerated dose and dose-limiting toxicities. The phase II portion enrolled patients into two arms to evaluate response and time-to-event end points: phase IIA (PIIA): ND-AML and phase IIB (PIIB): R/R-AML. RESULTS: Sixty-eight patients have enrolled to date (PIB, 16; PIIA, 29; PIIB, 23). Median age was 46 years (range, 20-73). Grade 3 and 4 adverse events occurring in ≥ 10% of patients included febrile neutropenia (50%), bacteremia (35%), pneumonia (28%), and sepsis (12%). The overall response rate for PIB, PIIA, and PIIB was 75%, 97%, and 70% with 75%, 90%, and 61%, respectively, achieving a composite CR. Measurable residual disease-negative composite CR was attained in 96% of ND-AML and 69% of R/R-AML patients. After a median follow-up of 12 months, median overall survival (OS) for both PII cohorts was not reached. Fifty-six percent of patients proceeded to allogeneic hematopoietic stem-cell transplantation (ND-AML, 69%; R/R-AML, 46%). In R/R-AML, allogeneic hematopoietic stem-cell transplantation resulted in a significant improvement in OS (median OS, NR; 1-year OS, 87%). One-year survival post-HSCT was 94% in ND-AML and 78% in R/R-AML. CONCLUSION: Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin + venetoclax represents an effective intensive treatment regimen in ND-AML and R/R-AML patients, associated with deep remissions and a high rate of transition to successful transplantation.

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