Dr Aldoss on MRD Negativity Outcomes With Ponatinib vs Imatinib in Newly Diagnosed Ph+ ALL

“For patients who didn’t achieve MRD negativity at the end of induction, they remain on [their respective] treatment. We observed that by the end of the treatment more patients who received ponatinib achieved MRD negativity compared with patients who received imatinib, and this also includes achieving deep molecular response.”

Ibrahim T. Aldoss, MD, an associate professor in the Division of Leukemia in the Department of Hematology & Hematopoietic Cell Transplantation at the City of Hope, discussed minimal residual disease (MRD) negativity outcomes following treatment with ponatinib (Iclusig) or imatinib (Gleevec) in patients with newly diagnosed Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).

The phase 3 PhALLCON trial (NCT03589326) evaluated the efficacy and safety of ponatinib vs imatinib plus reduced-intensity chemotherapy as first-line therapy for the treatment of patients with newly diagnosed Ph-positive ALL. Of note, patients who did not achieve MRD negativity at the end of induction (EOI) on the study remained on their respective treatments, Aldoss began. By the end of treatment, more patients who were treated with ponatinib achieved MRD negativity compared with those treated with imatinib, which also reflected achieving deep molecular response, he explained. Additionally, the MR4.5 MRD negativity was higher in the ponatinib arm vs the imatinib arm, he stated. By the end of treatment, the MR4.5 rates were 37% in the ponatinib arm vs 10% in the imatinib arm, according to Aldoss. He also noted that patients who did not achieve MRD negativity at the EOI, who remained on treatment, demonstrated superior event-free survival (EFS) and overall survival in the ponatinib arm compared with the imatinib arm. Specifically, the 2-year EFS rates were 87% (95% CI, 72%-94%) and 62% (95% CI, 36%-80%) in the ponatinib vs imatinib arms, respectively, he highlighted.

Furthermore, Aldoss explained that the safety profiles of the respective treatments were comparable, with similar rates of treatment-emergent adverse effects (TEAEs) among patients treated with ponatinib and imatinib. Moreover, TEAEs leading to dose modification in patients who did not achieve MRD negativity by EOI were observed in 71% and 54% of patients in the ponatinib (n = 61 of 86) and imatinib (n = 29 of 54) arms, respectively.