ATLANTA—Ponatinib has substantial activity and is generally well tolerated in heavily pretreated patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) resistant or intolerant to dasatinib or nilotinib, or with the T315I BCR-ABL mutation, according to a 12-month follow-up analysis reported during the 54th American Society of Hematology Annual Meeting and Exposition.

The efficacy and safety of oral ponatinib 45mg/day is being evaluated in the pivotal phase 2, global, open-label PACE trial of 449 patients with CML accelerated phase (AP), blast phase (BP), and chronic phase (CP) or Ph+ ALL. Median age is 60 years (range, 18-94 years). The primary endpoint is major cytogenic response (MCyR) at any time within 12 months for CML-CP and major hematologic response (MaHR) at any time within 6 months for advanced Ph+ ALL.

Ponatinib, a potent pan-BCR-ABL inhibitor, is active against native and mutated forms of BCR-ABL, including the tyrosine kinase inhibitor (TKI)-resistant T315I mutant.

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”Ponatinib may be an important new treatment for CML and Ph+ ALL resistant or intolerant to prior TKIs,” reported Jorge E. Cortes, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, and colleagues.

The best prior response to most recent dasatinib or nilotinib was 26% MCyR or better in CML-CP, and 24% MaHR or better in advanced Ph+ ALL.

Median time from diagnosis to ponatinib was 7 years (range, 0.3 to 28 years). Responses were durable; estimated probability of responders maintaining the primary endpoint at 1 year was 91% in CML-CP, 42% in CML-AP, and 35% in CML-BP/Ph+ ALL. In CP-CML, 46% had complete cytogenetic response; molecular responses were “early and deep,” with rates of 34% MMR and 15% MR4.5, with “91% estimated to remain in MCyR at 1 year,” Dr. Cortes said.

CMS-CP progression-free survival (PFS) and overall survival (OS) at 1 year were 80% and 94%, respectively; the median has not been reached in either case, Dr. Cortes noted.

“Response rates were higher in patients exposed to fewer prior TKIs and those with shorter disease duration,” Dr. Cortes reported, and similar response rates were observed in patients with and without BCR-ABL mutations.