Gimema All2820 phase 3: ponatinib plus blinatumomab without chemotherapy gave 86% two-year event-free survival

The Gimema All2820 phase 3 trial compared a chemotherapy-free regimen with standard treatment in adults with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). The results were published in the New England Journal of Medicine, according to a statement reported by adnkronos.com adnkronos.comadnkronos.comadnkronos.comOpen source ↗. The trial was coordinated by Sabina Chiaretti and Robin Foà of Sapienza University of Rome and sponsored by Fondazione Gimema – Franco Mandelli Ets.

Trial design

From September 2021 to January 2025, the trial enrolled 236 adults aged 24 to 82. A total of 158 patients received the experimental regimen and 78 received standard treatment. The experimental arm received the third-generation tyrosine kinase inhibitor ponatinib, followed by 2 to 5 intravenous cycles of the bispecific antibody blinatumomab. The standard arm received the inhibitor imatinib with chemotherapy.

The primary endpoint was event-free survival. It accounts for survival, hematologic response, persistence of disease at the molecular level and events such as relapse. Molecular response, which detects very small amounts of residual disease, received particular attention.

Reported results

At two years, 86% of patients on ponatinib and blinatumomab had had no adverse event, compared with 67% on standard treatment adnkronos.comadnkronos.comadnkronos.comOpen source ↗. After induction, 94% of the experimental group had reached complete hematologic remission, versus 79% in the standard group. After consolidation with blinatumomab, molecular response was reached by 71% of patients treated without chemotherapy and 49% of those on the standard regimen.

Two-year overall survival was 90% in the experimental group and 85% in the standard group. The cumulative probability of relapse was 5% and 13%, respectively. The statement also says the regimen reduced side effects.

Background

Ph+ ALL is caused by a chromosomal translocation that fuses the BCR and ABL1 genes. The resulting fusion protein promotes uncontrolled cell proliferation. For a long time, chemotherapy and allogeneic hematopoietic stem cell transplantation were the mainstays of treatment, and tyrosine kinase inhibitors have been used since the early 2000s. In 2000 the Gimema group started the Lal0201 study, one of the first protocols using imatinib without chemotherapy during induction. Later Gimema studies explored first-, second- and third-generation inhibitors.

Foà said the study provides solid evidence for a possible change of paradigm in treating adult Ph+ ALL adnkronos.comadnkronos.comadnkronos.comOpen source ↗.