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Journal Article Epublish 5 citations

PubMed: 37567878 DOI: 10.1038/s41408-023-00891-x

Real-world experience with ponatinib therapy in chronic phase chronic myeloid leukemia: impact of depth of response on survival and prior exposure to nilotinib on arterial occlusive events.

Blood Cancer J 13(1):122

Authors: Maymona G Abdelmagid, Aref Al-Kali, Mark R Litzow, Kebede H Begna, William J Hogan, Mirinal S Patnaik, Shahrukh K Hashmi, Michelle A Elliott, Hassan Alkhateeb, Omer S Karrar, Farah Fleti, Mohammed H Elnayir, Candido E Rivera, Hemant S Murthy, James M Foran, Mohamed A Kharfan-Dabaja, Talha Badar, David S Viswanatha, Kaaren K Reichard, Naseema Gangat, Ayalew Tefferi

Affiliations

  • Division of Hematology, Mayo Clinic, Rochester, MN, USA.
  • Division of Hematology, Mayo Clinic, Jacksonville, FL, USA.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Abstract

We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1T315I. At start of ponatinib (median dose 30 mg/day), 40 patients were already in complete hematologic (CHR), 4 in complete cytogenetic (CCyR), 3 in major molecular (MMR) remission, while 8 had not achieved CHR (NR). Ponatinib improved the depth of response in 13 (33%), 3 (75%), 2 (66%), and 4 (50%) patients with CHR, CCyR, MMR, and NR, respectively (p = 0.02). At a median follow-up of 42 months, 13 (23%) deaths, 5 (9%) blast transformations, and 25 (45%) allogeneic transplants were recorded. Five/10-year post-ponatinib survival was 77%/58% with no significant difference when patients were stratified by allogeneic transplant (p = 0.94), ponatinib-induced deeper response (p = 0.28), or a post-ponatinib ≥CCyR vs CHR remission state (p = 0.25). ABL1T315I was detrimental to survival (p = 0.04) but did not appear to affect response. Prior exposure to nilotinib was associated with higher risk of arterial occlusive events (AOEs; 11% vs 0%; age-adjusted p = 0.04). Ponatinib starting/maintenance dose (45 vs 15 mg/day) did not influence either treatment response or AOEs. Our observations support the use of a lower starting/maintenance dose for ponatinib in relapsed/refractory CML-CP but a survival advantage for deeper responses was not apparent and treatment might not overcome the detrimental impact of ABL1T315I on survival. The association between prior exposure to nilotinib and a higher risk of post-ponatinib AOEs requires further validation.

MeSH

Risk, Leukemia, Myelogenous, Chronic, Bcr-Abl Positive, Therapeutics, Maintenance, Transplants, Allografts, Leukemia, Myeloid, Chronic-Phase

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