TY - JOUR
T1 - 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
AU - Sasaki, Koji
AU - Kantarjian, Hagop M.
AU - Short, Nicholas J.
AU - Samra, Bachar
AU - Khoury, Joseph D.
AU - Kanagal Shamanna, Rashmi
AU - Konopleva, Marina
AU - Jain, Nitin
AU - DiNardo, Courtney D.
AU - Khouri, Rita
AU - Garcia-Manero, Guillermo
AU - Kadia, Tapan M.
AU - Wierda, William G.
AU - Khouri, Issa F.
AU - Kebriaei, Partow
AU - Mehta, Rohtesh S.
AU - Champlin, Richard E.
AU - Garris, Rebecca
AU - Cheung, Cora Marie
AU - Daver, Naval
AU - Thompson, Philip A.
AU - Yilmaz, Musa
AU - Ravandi, Farhad
AU - Jabbour, Elias
N1 - Publisher Copyright:
© 2021 American Cancer Society
PY - 2021/8/1
Y1 - 2021/8/1
N2 - 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.
AB - 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.
KW - Philadelphia chromosome-positive
KW - acute lymphoblastic leukemia
KW - allogeneic stem cell transplant
KW - complete molecular response
KW - tyrosine kinase inhibitors
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U2 - 10.1002/cncr.33529
DO - 10.1002/cncr.33529
M3 - Article
C2 - 33793964
AN - SCOPUS:85103390194
SN - 0008-543X
VL - 127
SP - 2648
EP - 2656
JO - Cancer
JF - Cancer
IS - 15
ER -