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

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 DaverPhilip A. Thompson, Musa Yilmaz, Farhad Ravandi, Elias Jabbour

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2648-2656
Number of pages9
JournalCancer
Volume127
Issue number15
DOIs
StatePublished - Aug 1 2021
Externally publishedYes

Keywords

  • Philadelphia chromosome-positive
  • acute lymphoblastic leukemia
  • allogeneic stem cell transplant
  • complete molecular response
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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