Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia

Andrew M. Stein, Giovanni Martinelli, Timothy P. Hughes, Martin C. Müller, Lan Beppu, Enrico Gottardi, Susan Branford, Simona Soverini, Richard C. Woodman, Andreas Hochhaus, Dong Wook Kim, Giuseppe Saglio, Jerald P. Radich

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be used to predict long-term responses.Methods: Patients from the nilotinib registration trial (CAMN107A2101; registered at http://www.clinicaltrials.gov as NCT00109707) who had imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase with BCR-ABL1 > 10% (on the international scale [IS]) at baseline and, in the first 6 months, had at least three BCR-ABL1 transcript measurements and an average daily dose of at least 720 mg were included in this analysis (N = 123).Results: More than half of patients (65/123; 53%) had a slow monophasic response and the remainder (58/123; 47%) had a biphasic response, in which patients had a rapid initial decrease in BCR-ABL1 transcripts followed by a more gradual response. The biphasic response type strongly correlated with improved event-free survival (EFS). Data in the first 6 months of follow-up were sufficient to predict EFS at 24 months.Conclusions: Unlike newly diagnosed patients with Ph+ CML-CP-in whom the majority had a biphasic response-approximately half of patients with imatinib-resistant or -intolerant CML had a slower, monophasic response. Second-line patients who did have a biphasic response had an EFS outlook similar to that of newly diagnosed patients treated with imatinib. Our model was comparable to using BCR-ABL1 (IS) ≤ 10% at 6 months as a threshold for predicting EFS.

Original languageEnglish
Article number173
JournalBMC cancer
Volume13
DOIs
Publication statusPublished - 2 Apr 2013

Keywords

  • BCR-ABL
  • Chronic myeloid leukemia
  • Mathematical modeling
  • Molecular response
  • Nilotinib

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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