Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations

Authors

Daniel A Pollyea
Courtney D DiNardo
Martha L Arellano
Arnaud Pigneux
Walter Fiedler
Marina Konopleva
David A Rizzieri
B Douglas Smith
Atsushi Shinagawa
Roberto M Lemoli
Monique Dail
Yinghui Duan
Brenda Chyla
Jalaja Potluri
Catherine L Miller
Hagop M Kantarjian

Publication Date

7-1-2022

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-21-3467

PMID

35046058

PMCID

PMC9365354

PubMedCentral® Posted Date

1-18-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).

Patients and methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle).

Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group.

Conclusions: Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut. See related commentary by Perl and Vyas, p. 2719.

Keywords

Aged, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Bridged Bicyclo Compounds, Heterocyclic, Dancing, Humans, Isocitrate Dehydrogenase, Leukemia, Myeloid, Acute, Mutation, Sulfonamides

Published Open-Access

yes

Recommended Citation

Pollyea, Daniel A; DiNardo, Courtney D; Arellano, Martha L; et al., "Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations" (2022). Faculty, Staff and Student Publications. 2971.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/2971