TY - JOUR
T1 - Efficacy of Ponatinib Versus Earlier Generation Tyrosine Kinase Inhibitors for Front-line Treatment of Newly Diagnosed Philadelphia-positive Acute Lymphoblastic Leukemia
AU - Jabbour, Elias
AU - DerSarkissian, Maral
AU - Duh, Mei Sheng
AU - McCormick, Nora
AU - Cheng, Wendy Y.
AU - McGarry, Lisa J.
AU - Souroutzidis, Ariadne
AU - Huang, Hui
AU - O'Brien, Susan
AU - Ravandi, Farhad
AU - Kantarjian, Hagop M.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/4
Y1 - 2018/4
N2 - The complete molecular response (CMR) and overall survival (OS) in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia treated with front-line chemotherapy plus ponatinib versus earlier generation tyrosine kinase inhibitors were compared in a meta-analysis and meta-regression. The patients treated with front-line ponatinib versus earlier generation treatments were more likely to achieve a CMR and had greater rates of 3-year OS. Introduction: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib). Patients and Methods: We identified 26 Ph+ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib. The outcomes from studies of combination chemotherapy plus earlier generation TKIs were summarized using pooled estimates with 95% confidence intervals (CIs) from a random-effects meta-analysis. A binomial distribution was assumed to calculate the 95% CIs for the results from the single-arm combination chemotherapy plus ponatinib trial. Adjusted logistic meta-regression analyses were used to compare the outcomes between the TKI groups. Results: The percentage of patients achieving a CMR was greater with combination chemotherapy plus ponatinib (79%) than the pooled percentage of patients achieving a CMR with combination chemotherapy plus earlier generation TKIs (34%). Greater OS was observed with ponatinib compared with the pooled OS for earlier generation TKIs (2-year, 83% vs. 58%; 3-year, 79% vs. 50%). Odds ratios for ponatinib versus earlier generation TKIs were 6.09 (95% CI, 1.16-31.90; P =.034) for CMR, 3.70 (95% CI, 0.93-14.73; P =.062) for 2-year OS, and 4.49 (95% CI, 1.00-20.13; P =.050) for 3-year OS. Conclusion: Ponatinib plus chemotherapy might be associated with better outcomes than chemotherapy with earlier generation TKIs in patients with newly diagnosed Ph+ ALL.
AB - The complete molecular response (CMR) and overall survival (OS) in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia treated with front-line chemotherapy plus ponatinib versus earlier generation tyrosine kinase inhibitors were compared in a meta-analysis and meta-regression. The patients treated with front-line ponatinib versus earlier generation treatments were more likely to achieve a CMR and had greater rates of 3-year OS. Introduction: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib). Patients and Methods: We identified 26 Ph+ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib. The outcomes from studies of combination chemotherapy plus earlier generation TKIs were summarized using pooled estimates with 95% confidence intervals (CIs) from a random-effects meta-analysis. A binomial distribution was assumed to calculate the 95% CIs for the results from the single-arm combination chemotherapy plus ponatinib trial. Adjusted logistic meta-regression analyses were used to compare the outcomes between the TKI groups. Results: The percentage of patients achieving a CMR was greater with combination chemotherapy plus ponatinib (79%) than the pooled percentage of patients achieving a CMR with combination chemotherapy plus earlier generation TKIs (34%). Greater OS was observed with ponatinib compared with the pooled OS for earlier generation TKIs (2-year, 83% vs. 58%; 3-year, 79% vs. 50%). Odds ratios for ponatinib versus earlier generation TKIs were 6.09 (95% CI, 1.16-31.90; P =.034) for CMR, 3.70 (95% CI, 0.93-14.73; P =.062) for 2-year OS, and 4.49 (95% CI, 1.00-20.13; P =.050) for 3-year OS. Conclusion: Ponatinib plus chemotherapy might be associated with better outcomes than chemotherapy with earlier generation TKIs in patients with newly diagnosed Ph+ ALL.
KW - Combination therapy
KW - Complete molecular response
KW - Meta-analysis
KW - Meta-regression
KW - Overall survival
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U2 - 10.1016/j.clml.2018.02.010
DO - 10.1016/j.clml.2018.02.010
M3 - Article
C2 - 29519619
AN - SCOPUS:85042853582
SN - 2152-2650
VL - 18
SP - 257
EP - 265
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -