An imatinib-only window followed by imatinib and chemotherapy for Philadelphia chromosome-positive acute leukemia: Long-term results of the CMLALL1 trial

Jason D. Lickliter, Kerry Taylor, Jeff Szer, Andrew Grigg, Christopher Arthur, Timothy P. Hughes, Simon Durrant, Robin Filshie, Ian Irving, Michael Seldon, Jennifer Ellacott, Andrew W. Boyd, James D'Rozario, Kim Rooney, Kevin Lynch, Ken Bradstock, Australasian Leukaemia and Lymphoma Group

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph+) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCRABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph+ acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens. Cohort 2 had a complete response (CR) rate of 93% and 5-year survival of 69%. For newly diagnosed Ph+ ALL, survival was superior in cohort 2 compared with cohort 1. Toxicity was similar to that expected for chemotherapy alone. Among 10 evaluable patients, rapid loss of phospho-CRKL occurred during the imatinib window in seven patients (all achieved CR) and incomplete inhibition in three patients (none with CR). In summary, a pharmacodynamic window design permitted biomarker assessment of BCRABL targeting without compromising clinical outcomes.

Original languageEnglish
Pages (from-to)630-638
Number of pages9
JournalLeukemia and Lymphoma
Volume56
Issue number3
DOIs
Publication statusPublished or Issued - 1 Mar 2015

Keywords

  • Chemotherapeutic approaches
  • lymphoid leukemia
  • pharmacotherapeutics
  • signaling therapies

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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