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Prognostic factors for progression in patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia in complete molecular response within 3 months of therapy with tyrosine kinase inhibitors
Author(s) -
Sasaki Koji,
Kantarjian Hagop M.,
Short Nicholas J.,
Samra Bachar,
Khoury Joseph D.,
Kanagal Shamanna Rashmi,
Konopleva Marina,
Jain Nitin,
DiNardo Courtney D.,
Khouri Rita,
GarciaManero Guillermo,
Kadia Tapan M.,
Wierda William G.,
Khouri Issa F.,
Kebriaei Partow,
Mehta Rohtesh S.,
Champlin Richard E.,
Garris Rebecca,
Cheung Cora Marie,
Daver Naval,
Thompson Philip A.,
Yilmaz Musa,
Ravandi Farhad,
Jabbour Elias
Publication year - 2021
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.33529
Subject(s) - medicine , ponatinib , dasatinib , imatinib , hazard ratio , oncology , vincristine , philadelphia chromosome , cyclophosphamide , chemotherapy , myeloid leukemia , chromosomal translocation , confidence interval , biochemistry , chemistry , gene
BACKGROUND The achievement of a 3‐month complete molecular response (CMR) is a major prognostic factor for survival in patients with Philadelphia chromosome (Ph)‐positive acute lymphoblastic leukemia (ALL). However, 25% of patients relapse during therapy with tyrosine kinase inhibitors (TKIs). METHODS The authors reviewed 204 patients with Ph‐positive ALL who were treated between January 2001 and December 2018 using the combination of hyper‐CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus a TKI (imatinib, 44 patients [22%]; dasatinib, 88 patients [43%]; or ponatinib, 72 patients [35%]). Progression‐free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or last follow‐up. Overall survival (OS) was defined as the time from the start date of therapy to the date of death or last follow‐up. RESULTS Overall, a 3‐month CMR was observed in 57% of patients, including 32% of those who received imatinib, 52% of those who received dasatinib, and 74% of those who received ponatinib. The median follow‐up was 74 months (imatinib, 180 months; dasatinib, 106 months; ponatinib, 43 months). Among 84 patients in 3‐month CMR, 17 (20%) proceeded to undergo allogeneic stem cell transplantation (ASCT). The 5‐year PFS and OS rates were 68% and 72%, respectively. By multivariate analysis, ponatinib therapy was the only significant favorable independent factor predicting for progression ( P = .028; hazard ratio, 0.388; 95% CI, 0.166‐0.904) and death ( P = .042; hazard ratio, 0.379; 95% CI, 0.149‐0.966). ASCT was not a prognostic factor for PFS and OS by univariate analysis. CONCLUSIONS In patients with Ph‐positive ALL, ponatinib is superior to other types of TKIs in inducing and maintaining a CMR, thus preventing disease progression. ASCT does not improve outcome once a 3‐month CMR is achieved.