TY - JOUR
T1 - Ponatinib after failure of second-generation tyrosine kinase inhibitor in resistant chronic-phase chronic myeloid leukemia
AU - Kantarjian, Hagop M.
AU - Jabbour, Elias
AU - Deininger, Michael
AU - Abruzzese, Elisabetta
AU - Apperley, Jane
AU - Cortes, Jorge
AU - Chuah, Charles
AU - DeAngelo, Daniel J.
AU - DiPersio, John
AU - Hochhaus, Andreas
AU - Lipton, Jeffrey
AU - Nicolini, Franck E.
AU - Pinilla-Ibarz, Javier
AU - Rea, Delphine
AU - Rosti, Gianantonio
AU - Rousselot, Philippe
AU - Shah, Neil P.
AU - Talpaz, Moshe
AU - Srivastava, Shouryadeep
AU - Ren, Xiaowei
AU - Mauro, Michael
N1 - Publisher Copyright:
© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2022/11
Y1 - 2022/11
N2 - Ponatinib, the only third-generation pan-BCR::ABL1 inhibitor with activity against all known BCR::ABL1 mutations including T315I, has demonstrated deep and durable responses in patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to prior second-generation (2G) TKI treatment. We present efficacy and safety outcomes from the Ponatinib Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and CML Evaluation (PACE) and Optimizing Ponatinib Treatment in CP-CML (OPTIC) trials for this patient population. PACE (NCT01207440) evaluated ponatinib 45 mg/day in CML patients with resistance to prior TKI or T315I. In OPTIC (NCT02467270), patients with CP-CML and resistance to ≥2 prior TKIs or T315I receiving 45 or 30 mg/day reduced their doses to 15 mg/day upon achieving ≤1% BCR::ABL1IS or received 15 mg/day continuously. Efficacy and safety outcomes from patients with CP-CML treated with ≥1 2G TKI (PACE, n = 257) and OPTIC (n = 93), 45-mg starting dose cohort, were analyzed for BCR::ABL1IS response rates, overall survival (OS), progression-free survival (PFS), and safety. By 24 months, the percentages of patients with ≤1% BCR::ABL1IS response, PFS, and OS were 46%, 68%, and 85%, respectively, in PACE and 57%, 80%, and 91%, respectively, in OPTIC. Serious treatment-emergent adverse events and serious treatment-emergent arterial occlusive event rates were 63% and 18% in PACE and 34% and 4% in OPTIC. Ponatinib shows high response rates and robust survival outcomes in patients whose disease failed prior to 2G TKIs, including patients with T315I mutation. The response-based dosing in OPTIC led to improved safety and similar efficacy outcomes compared with PACE.
AB - Ponatinib, the only third-generation pan-BCR::ABL1 inhibitor with activity against all known BCR::ABL1 mutations including T315I, has demonstrated deep and durable responses in patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to prior second-generation (2G) TKI treatment. We present efficacy and safety outcomes from the Ponatinib Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and CML Evaluation (PACE) and Optimizing Ponatinib Treatment in CP-CML (OPTIC) trials for this patient population. PACE (NCT01207440) evaluated ponatinib 45 mg/day in CML patients with resistance to prior TKI or T315I. In OPTIC (NCT02467270), patients with CP-CML and resistance to ≥2 prior TKIs or T315I receiving 45 or 30 mg/day reduced their doses to 15 mg/day upon achieving ≤1% BCR::ABL1IS or received 15 mg/day continuously. Efficacy and safety outcomes from patients with CP-CML treated with ≥1 2G TKI (PACE, n = 257) and OPTIC (n = 93), 45-mg starting dose cohort, were analyzed for BCR::ABL1IS response rates, overall survival (OS), progression-free survival (PFS), and safety. By 24 months, the percentages of patients with ≤1% BCR::ABL1IS response, PFS, and OS were 46%, 68%, and 85%, respectively, in PACE and 57%, 80%, and 91%, respectively, in OPTIC. Serious treatment-emergent adverse events and serious treatment-emergent arterial occlusive event rates were 63% and 18% in PACE and 34% and 4% in OPTIC. Ponatinib shows high response rates and robust survival outcomes in patients whose disease failed prior to 2G TKIs, including patients with T315I mutation. The response-based dosing in OPTIC led to improved safety and similar efficacy outcomes compared with PACE.
UR - http://www.scopus.com/inward/record.url?scp=85137258507&partnerID=8YFLogxK
U2 - 10.1002/ajh.26686
DO - 10.1002/ajh.26686
M3 - Article
C2 - 36054756
AN - SCOPUS:85137258507
SN - 0361-8609
VL - 97
SP - 1419
EP - 1426
JO - American journal of hematology
JF - American journal of hematology
IS - 11
ER -