Details

Autor(en) / Beteiligte

• Othman, Tamer
• Koller, Paul
• Tsai, Ni-Chun
• Yang, Dongyun
• Pourhassan, Hoda
• Agrawal, Vaibhav
• Ngo, Dat
• Chen, Jason
• Farol, Leonardo
• Spielberger, Ricardo
• Sahebi, Firoozeh
• Al Malki, Monzr M
• Cai, Ji-Lian
• Sandhu, Karamjeet S
• Mansour, Joshua
• Salhotra, Amandeep
• Ali, Haris
• Aribi, Ahmed
• Arslan, Shukaib
• Marcucci, Guido
• Forman, Stephen J
• Stein, Anthony S
• Nakamura, Ryotaro
• Pullarkat, Vinod
• Aldoss, Ibrahim
• Mei, Matthew

Titel

Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia

Ist Teil von

• American journal of hematology, 2024-05

Ort / Verlag

United States

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but published clinical experience is primarily with the first-generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope. Initially, 50 (27.0%) received imatinib, 118 (63.8%) received a second-generation TKI (2G-TKI), and 17 (9.2%) received ponatinib. A total of 77 patients (41.6%) required a dose reduction of their initial TKI due to toxicity. Sixty-six patients (35.7%) did not complete maintenance due to toxicity; 69 patients (37.3%) discontinued 1 TKI, and 11 (5.9%) discontinued 2 TKIs due to toxicity. Initial imatinib versus 2G-TKI versus ponatinib maintenance was discontinued in 19 (38.0%) versus 68 (57.6%) versus 3 (17.6%) patients due to toxicity (p = .003), respectively. Patients on ponatinib as their initial TKI had a longer duration of TKI maintenance versus 2G-TKI: 576.0 days (range, 72-921) versus 254.5 days (range, 3-2740; p = .02). The most common reasons for initial TKI discontinuation include gastrointestinal (GI) intolerance (15.1%), cytopenia (8.6%), and fluid retention (3.8%). The 5-year overall survival and progression-free survival for the total population were 78% and 71%, respectively. Our findings demonstrate the challenges of delivering post-HCT TKI maintenance in a large real-world cohort as toxicities leading to TKI interruptions, discontinuation, and dose reduction were common.