The Outcomes of Patients With Chronic Myeloid Leukemia Treated With Third-Line BCR::ABL1 Tyrosine Kinase Inhibitors

Authors

Elias J Jabbour
Koji Sasaki
Fadi G Haddad
Ghayas C Issa
Guillermo Garcia-Manero
Tapan M Kadia
Nitin Jain
Musa Yilmaz
Courtney D DiNardo
Keyur P Patel
Rashmi Kanagal-Shamanna
Richard Champlin
Issa F Khouri
Sara Dellasala
Sherry A Pierce
Hagop Kantarjian

Publication Date

4-1-2023

Journal

American Journal of Hematology

Abstract

The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with chronic myeloid leukemia (CML). After failing second-generation TKI (2G-TKI), the optimal third-line therapy in chronic phase CML (CML-CP) is not well established. We analyzed 354 patients with CML-CP treated with a third-line BCR::ABL1 TKI at our institution, and in the PACE and OPTIC trials, and evaluated the outcome after alternate 2G-TKIs or ponatinib. We performed a propensity score matching analysis to compare outcomes and multivariate analysis to identify variables associated with survival. One hundred seventy-three (49%) patients received 2G-TKIs and 181 (51%) ponatinib. Patients in the ponatinib group had more cardiovascular risk factors (34% versus 19%) and higher disease burden (BCR::ABL1 transcript levels >1%, 165/175 [94%] versus 75/135 [55%]; p < .001) compared with the 2G-TKI group. Among the 173 evaluable patients treated with ponatinib, 89 (52%) achieved 2 + -log reduction of baseline transcripts (20% 2-log reduction and 32% 3 + -log reduction). Among the 128 evaluable patients treated with 2G-TKIs, 44 (34%) achieved 2 + -log reduction of baseline transcripts (13% 2-log reduction and 21% 3 + -log reduction). With a median follow-up of 46 months, the 3-year progression-free survival was 59% (60% before matching) with 2G-TKI and 83% (81% before matching) with ponatinib (p < .001). The 3-year survival was 83% (81% before matching) with 2G-TKI and 87% (89% before matching) with ponatinib (p = .03). By multivariate analysis, third-line therapy with ponatinib was the only independent factor associated with better survival (p = .003). In conclusion, ponatinib is an optimal treatment for patients with CML-CP failing two prior TKIs.

Keywords

Humans, Tyrosine Kinase Inhibitors, Protein Kinase Inhibitors, Fusion Proteins, bcr-abl, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase, Drug Resistance, Neoplasm

DOI

10.1002/ajh.26852

PMID

36683287

PMCID

PMC11576052

PubMedCentral® Posted Date

11-19-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes