Venetoclax Abrogates the Prognostic Impact of Splicing Factor Gene Mutations in Newly Diagnosed Acute Myeloid Leukemia

Authors

Jayastu Senapati
Samuel Urrutia
Sanam Loghavi
Nicholas J Short
Ghayas C Issa
Abhishek Maiti
Hussein A Abbas
Naval G Daver
Naveen Pemmaraju
Sherry Pierce
Kelly S Chien
Koji Sasaki
Tapan M Kadia
Danielle E Hammond
Gautam Borthakur
Keyur Patel
Farhad Ravandi
Hagop M Kantarjian
Guillermo Garcia-Manero
Courtney D DiNardo

Publication Date

11-9-2023

Journal

Blood

DOI

10.1182/blood.2023020649

PMID

37441846

Abstract

Mutations in splicing factor (SF) genes SRSF2, U2AF1, SF3B1, and ZRSR2 are now considered adverse risk in the European LeukemiaNet 2022 acute myeloid leukemia (AML) risk stratification. The prognostic impact of SF mutations in AML has been predominantly derived from younger patients treated with intensive (INT) therapy. We evaluated 994 patients with newly diagnosed AML, including 266 (27%) with a SFmut. Median age was 67 years overall, with patients with SFmut being older at 72 years. SRSF2 (n = 140, 53%) was the most common SFmut. In patients treated with INT, median relapse-free survival (RFS) (9.6 vs 21.4 months, P = .04) and overall survival (OS) (15.9 vs 26.7 months, P = .06) were shorter for patients with SFmut than without SFwt, however this significance abrogated when evaluating patients who received venetoclax with INT therapy (RFS 15.4 vs 20.3 months, P = .36; OS 19.6 vs 30.7 months, P = .98). In patients treated with LI, median RFS (9.3 vs 7.7 months, P = .35) and OS (12.3 vs 8.5 months, P = .14) were similar for patients with and without SFmut , and outcomes improved in all groups with venetoclax. On multivariate analysis, SFmut did not affect hazards of relapse and death for INT arm but reduced both these hazards in LI arm. In a large AML data set with >60% of patients receiving venetoclax with LI/INT therapy, SFmut had no independent negative prognostic impact. Newer prognostic models that consider LI therapy and use of venetoclax among other factors are warranted.

Keywords

Humans, Aged, RNA Splicing Factors, Prognosis, Serine-Arginine Splicing Factors, Splicing Factor U2AF, Leukemia, Myeloid, Acute, Mutation

Published Open-Access

yes

Recommended Citation

Senapati, Jayastu; Urrutia, Samuel; Loghavi, Sanam; et al., "Venetoclax Abrogates the Prognostic Impact of Splicing Factor Gene Mutations in Newly Diagnosed Acute Myeloid Leukemia" (2023). Faculty, Staff and Student Publications. 4196.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4196