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.

Abstract

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.

• Authors: Koji Sasaki, Hagop M Kantarjian, Nicholas J Short, Bachar Samra, Joseph D Khoury, Rashmi Kanagal Shamanna, Marina Konopleva, Nitin Jain, Courtney D DiNardo, Rita Khouri, Guillermo Garcia-Manero, Tapan M Kadia, William G Wierda, Issa F Khouri, Partow Kebriaei, Rohtesh S Mehta, Richard E Champlin, Rebecca Garris, Cora Marie Cheung, Naval Daver, Philip A Thompson, Musa Yilmaz, Farhad Ravandi, Elias Jabbour
• Journal: Cancer (Cancer) Vol. 127 Issue 15 Pg. 2648-2656 (08 01 2021) ISSN: 1097-0142 [Electronic] United States
• PMID: 33793964 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 American Cancer Society.

Chemical References

• Protein Kinase Inhibitors

Topics

• Disease-Free Survival
• Hematopoietic Stem Cell Transplantation
• Humans
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Prognosis
• Protein Kinase Inhibitors (therapeutic use)