Impact of baseline mutations on response to ponatinib and end of treatment mutation analysis in patients with chronic myeloid leukemia.

7001 Background: BCR-ABL kinase domain mutations frequently cause tyrosine kinase inhibitor (TKI) failure in chronic myeloid leukemia (CML). Ponatinib, a potent oral pan-BCR-ABL TKI, has shown preclinical activity against all single mutants tested, including T315I. The impact of baseline (BL) mutations on response to ponatinib (45 mg once daily) and end of treatment (EOT) mutations in pts discontinuing treatment were evaluated in the phase II PACE trial. Methods: Heavily pretreated chronic phase (CP) CML pts (93% received ≥2 prior TKIs, 60% ≥3) resistant or intolerant to dasatinib or nilotinib (N=203) or with T315I confirmed at BL (N=64) were enrolled. The primary endpt was major cytogenetic response (MCyR). Min follow up at analysis (9 Nov 2012) was 12 mos (median 15 [0.1-25]). Sanger sequencing was done at one central laboratory. Results: At BL, no mutations were detected in 51% of pts, 1 mutation in 39%, and ≥2 mutations in 10%; 26 unique mutations were observed. Responses were observed regardless of B...