Survival outcomes in patients with chronic phase chronic myeloid leukemia (CP-CML) receiving third- or subsequent line (3L) treatment prior to the availability of ponatinib.

Abstract

e18553 Background: PACE was a phase 2 single-arm trial of ponatinib, a 3rd-generation tyrosine kinase inhibitor (TKI), in 449 highly-refractory patients with CML or Philadelphia-chromosome positive (Ph+) acute lymphocytic leukemia (ALL) or who had the BCR-ABL T315I mutation. Overall survival (OS) for 3L CP-CML patients in PACE at 1, 2, 3 and 4 years was estimated to be 91%, 83%, 80%, and 79%, respectively. Expected survival for 3L CP-CML patients prior to the availability of ponatinib has not been documented. Methods: A systematic literature review was conducted to estimate OS in patients with CP-CML receiving 3L treatment prior to ponatinib. Studies were identified from a review by Lipton et al. (2015), updated with studies identified from searches of electronic databases (MEDLINE, EMBASE, Cochrane Libraries) and abstract databases of key conferences. Landmark and median survival were extracted from study reports. Pseudo-individual patient data (IPD) for survival outcomes were derived from digitized Kaplan-Meier (KM) survival curves then pooled and analyzed using KM methods. Results: Fifteen studies (717 patients) were identified that reported median, landmark, or KM curves for survival outcomes for CP-CML patients receiving 3L treatment without ponatinib. KM curves for OS were obtained for 6 arms (3 nilotinib and/or dasatinib; 3 other TKIs). OS at 1, 2 and 3 years based on the pooled IPD is reported in the Table. To avoid confounding of OS from post-progression treatment with ponatinib, 1 study was excluded that included follow-up after the date of ponatinib’s approval. Conclusions: EstimatedOS in patients with CP-CML receiving 3L treatment prior to ponatinib appears to be shorter than that observed among ponatinib-treated patients in PACE: 4-year survival probability in PACE is higher than estimated 2-year survival probability prior to ponatinib. Further analyses are needed to identify and adjust for potentially confounding factors. [Table: see text]