Ponatinib appears more effective than imatinib for patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), according to research presented at the EHA 2023 Hybrid Congress.

In the phase 3 PHALLCON trial, patients who received ponatinib in combination with chemotherapy had a higher rate of minimal residual disease (MRD)-negative complete response (CR) than patients who received imatinib in combination with chemotherapy. Progression-free survival (PFS) was also superior in the ponatinib arm.

“Ponatinib plus reduced-intensity chemotherapy has the potential to be standard of care in patients with newly diagnosed, Philadelphia chromosome–positive ALL,” said study presenter Elias Jabbour, MD, of MD Anderson Cancer Center in Houston.

The PHALLCON trial (ClinicalTrials.gov Identifier: NCT03589326) included 245 patients with newly diagnosed Ph+ ALL. The patients were randomly assigned 2:1 to receive ponatinib (n=164) or imatinib (n=81), each in combination with reduced-intensity chemotherapy.

Baseline characteristics were similar between the arms. The median age was 54 years in the ponatinib arm and 52 years in the imatinib arm (overall range, 19-82 years). Slightly more than half of patients were women (55% and 53%, respectively), and most had an ECOG performance status of 0 or 1 (96% and 94%, respectively).

In both arms, induction consisted of the assigned tyrosine kinase inhibitor (TKI) plus vincristine and dexamethasone for 3 cycles. Consolidation consisted of 6 cycles of the assigned TKI plus methotrexate and cytarabine. Maintenance consisted of 11 cycles of the assigned TKI plus vincristine and prednisone. This was followed by the TKI alone until the end of the study.

The median follow-up was 20.4 months in the ponatinib arm and 18.1 months in the imatinib arm. At the data cutoff, 41% of patients in the ponatinib arm and 12% in the imatinib arm were still on treatment.

The primary endpoint was MRD-negative CR. The rate of MRD-negative CR was 34.4% in the ponatinib arm and 16.7% in the imatinib arm (relative risk, 2.06; 95% CI, 1.19-3.56; P =.0021). The rate of MRD negativity regardless of CR status was 41.6% and 20.5%, respectively (P =.0017).

The median duration of MRD negativity was not reached in the ponatinib arm and was 20.9 months in the imatinib arm. The median time to treatment failure was not reached and 21.9 months, respectively.

The proportion of patients who received subsequent therapy was 35% in the ponatinib arm and 57% in the imatinib arm. Sixteen percent of patients in the imatinib arm went on to receive ponatinib.

The median event-free survival was not reached with ponatinib and was 29.0 months with imatinib, though this difference did not reach statistical significance (hazard ratio [HR], 0.65; 95% CI, 0.39-1.10).

On the other hand, PFS was significantly improved in the ponatinib arm. The median PFS was 20.0 months in the ponatinib arm and 7.9 months in the imatinib arm (HR, 0.58; 95% CI. 0.41-0.83).

The median overall survival was not reached in either arm (HR, 0.76; 95% CI, 0.38-1.52).

The most common hematologic treatment-emergent adverse events (in the ponatinib and imatinib arms, respectively) were platelet count decrease (63% vs 58%), white blood cell count decrease (53% vs 49%), neutrophil count decrease (49% vs 46%), and lymphocyte count decrease (38% vs 47%).

The most common non-hematologic treatment-emergent adverse events in the entire cohort were headache (43%), nausea (40%), alanine transaminase increase (39%), pyrexia (34%), and constipation (32%).

Disclosures: This research was supported by Takeda. No other disclosures were provided.

Reference

Jabbour E, Kantarjian H, Aldoss I, et al. PHALLCON: A phase 3 study comparing ponatinib versus imatinib in newly diagnosed PH+ ALL. EHA 2023. June 8-11, 2023. Abstract SS10.

Ponatinib Plus Chemo May Be New Standard Care in Newly Diagnosed Ph+ ALL

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