Reference: January 2026 | Issue 1 | Vol 12 | Page 44
First results from the phase 3 GIMEMA ALL2820 trial suggest chemotherapy-free combination treatment outperforms a combination of targeted therapy and chemotherapy in patients with Ph+ acute lymphoblastic leukaemia (ALL).
The trial, which compared ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adults with ph+ ALL, is the first formal comparison of the efficacy and safety of these two approaches in newly diagnosed ph+ ALL.
Researchers say the findings offer reassurance that chemotherapy can be omitted without detrimental effects and suggest that a chemo-free targeted agent and immunotherapy combination could become the new standard of care
for this patient group.
The trial enrolled 236 adult with ph+ ALL, ranging in age from 19 to 84 years. Two-thirds of participants were randomly assigned to receive a TKI plus immunotherapy (experimental arm), and one-third were assigned to receive a TKI plus chemotherapy (control arm).
Patients in the experimental group received an initial course of steroids, 70-day induction with the TKI ponatinib, and two to five cycles of the immunotherapy blinatumomab. Patients in the control group received the TKI imatinib along with either four or six cycles of chemotherapy.
Patients in the experimental arm had a significantly higher rate of event-free survival (EFS) and a better response to treatment. At median follow-up of 23 months, EFS was 87 per cent in the experimental arm and 71 per cent in the control arm, while mortality was 3.5 per cent in the experimental arm and 10 per cent in the control arm.
The relapse rates were 6 per cent and 8 per cent, respectively, although about half of relapses in the experimental group occurred in patients who had discontinued treatment.
Complete remission was achieved in 94 per cent of those in the experimental arm and 79 per cent of those in the control group. The chemo-free treatment regimen also resulted in a higher rate of negative measurable residual disease (MRD) status.
While only 49 per cent of those in the control group achieved MRD-negative status, 71 per cent of those in the experimental group achieved MRD-negative status after two cycles of blinatumomab, and 80 per cent reached this status after five cycles.
“The chemo-free approach significantly reduced the rate of death in addition to increasing the rate of complete remission,” said lead study author, Prof Sabina Chiaretti, Sapienza University, Rome, Italy.
“The significance was very impressive, a more than 20 per cent difference in terms of molecular response achievement, so this approach truly is better.”
“The more cycles with blinatumomab, the more the molecular remission rate increased,” said Prof Chiaretti.
“This suggests that patients really should receive the planned five cycles. This is important because we have been working with blinatumomab for years, but we did not yet know how many cycles should be recommended.”
