CML-426: Outcomes of Patients with Blast Phase Chronic Myeloid Leukemia Following Ponatinib-Based Therapy

Consensus guidelines for the treatment of chronic myeloid leukemia in myeloid blast phase (CML-MBP) recommend acute myeloid leukemia-like chemotherapy in combination with a potent TKI such as ponatinib. However, the outcomes with this approach are not well established. Determine response rates and survival outcomes with ponatinib-based therapy (either monotherapy or in combination with chemotherapy) for CML-MBP, as well as the outcomes after ponatinib failure. Results: We identified 76 patients (pts) with CML-MBP who received a ponatinib-based regimen for CML-MBP between January 2008 and August 2023. The median age was 50 years. Fifty pts (66%) received ponatinib as first therapy for CML-MBP, and 26 pts (34%) as salvage therapy. Seventeen pts (22%) received ponatinib monotherapy, and the other 59 pts (78%) received it in combination with chemotherapy. For the entire cohort, the ORR (ie, CR/Cri/MLFS) was 49%. Twenty-eight percent of pts achieved complete cytogenetic response, and 20% achieved major molecular response or better. ORR was higher with ponatinib as first therapy for CML-MBP versus as salvage therapy (60% vs 27%, respectively; P = 0.003). ORR was also higher with combination therapy than with monotherapy (54% vs 29%, respectively; P = 0.06). Fifteen pts (20% overall) were bridged to allogeneic stem cell transplant (ASCT). For the entire cohort, the median RFS was 12 months, and the 2-year RFS was 33%; the median OS was 8.5 months, and the 2-year OS was 27%. Outcomes were better in patients who received ponatinib as first therapy for CML-MBP versus salvage (2-year OS: 33% vs 14%, respectively; P = 0.005). Among pts who achieved CR/CRi, the 2-year OS was 55%. In a landmark analysis, responding pts who underwent ASCT had superior outcomes compared with those who did not (2-year OS: 71% vs 38%, respectively; P = 0.06). Overall, 49 pts (64%) experienced failure of the ponatinib-based regimen (refractory, n = 31; relapse, n = 18). Outcomes were very poor following ponatinib failure, with a median OS of 3.9 months. Ponatinib-based therapies are effective in CML-MBP, especially when used as the first therapy for CML-MBP and when given in combination with chemotherapy. Pts should be bridged to ASCT to have the best outcomes. Outcomes after ponatinib failure are dismal, and new therapies are needed for these pts.