CONFERENCE UPDATE: ASH 2025

Ponatinib + blinatumomab vs. imatinib + chemotherapy in newly diagnosed adult Ph+ ALL: First results from the GIMEMA ALL2820 trial

HEMATOLOGY
30 Jan 2026

STUDY DESIGN

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) historically carried the worst outcomes among hematologic malignancies.1 The introduction of tyrosine kinase inhibitors (TKIs) in induction, followed by immunotherapy with blinatumomab in consolidation, has enabled chemotherapy-free treatment strategies.1 The GIMEMA phase 3 ALL2820 trial was designed to compare the efficacy and safety of a chemo-free approach with ponatinib + blinatumomab vs. a conventional TKI + chemotherapy regimen in adults with newly diagnosed Ph+ ALL (≥18 years with no upper age limit).1

This randomized 2:1 trial enrolled 236 patients, all of whom received a steroid pre-phase prior to randomization.1 Afterward, 158 patients were assigned to the experimental arm, which consisted of a 70-day induction with ponatinib at 45mg/day or 30mg/day according to age (<65 or ≥65 years), followed by at least two cycles (maximum five) of intravenous blinatumomab.1 The control arm included 78 patients who received imatinib at 800mg or 600mg daily, depending on age (<65 or ≥65 years), in combination with chemotherapy for six or four cycles, respectively.1 A crossover to the experimental arm was allowed in MRD+ patients after cycle 4/6, or earlier in case of refractoriness or mutation development.1

Key baseline characteristics were balanced across arms: median age 57 vs. 55 years, male gender 50% vs. 59%, IKZF1plus 34% vs. 26%, and CNS+ at diagnosis 9.9% vs. 15% in experimental and control arms, respectively.1

The first results presented assessed complete hematologic remission (CHR), measurable residual disease (MRD) response, safety and toxicity after induction (day +70) and after 2 blinatumomab/therapy cycles (day +133), and event-free survival (EFS).1

FINDINGS

Efficacy outcomes:
  • At the end of induction:
    • CHR was achieved in 149/158 patients (94.3%) in the experimental arm compared with 62/78 patients (79.4%) in the control arm1
    • Overall molecular responses at the end of induction were 46.8% in the experimental arm vs. 43.6% in the control arm, which was not statistically significant1
  • After two cycles of blinatumomab:
    • The overall molecular responses increased to 70.9% in the experimental arm compared with 48.7% in the control arm (p<0.001)1
  • 31 patients crossed over to blinatumomab + ponatinib, including one for refractoriness and three for early mutation development1
    • Of the crossover patients, 20 achieved MRD negativity, with 15 becoming negative after the first blinatumomab cycle and five after the second cycle1
    • 14 crossover patients subsequently underwent allogeneic stem cell transplantation1
  • The median time to relapse was 5.6 months in the experimental arm vs. 11.3 months in the control arm1
  • At a median follow-up of 23.4 months, EFS was 90% (95% CI: 86-95) in the experimental arm compared with 74% (95% CI:65-85) in the control arm (p=0.0015). Overall survival (OS) rate was 94% (95% CI: 91-98) in the experimental arm, 97% (95% CI: 90-100) among crossover patients, and 77% (95% CI: 66-91) in the control arm (p=0.00071)1

Safety:
  • In the experimental arm, 109 patients (68.9%) experienced adverse events (AEs), including 171 grade ≥3 events in 85 patients (53.8%) and 96 serious AEs in 49 patients (27.5%), with hematologic toxicity, hepatic toxicity, and infections being the most common
  • In the control arm, 53 patients (67.9%) experienced AEs, including 121 grade ≥3 events in 44 patients (56.4%) and 54 serious AEs in 34 patients (50%), most commonly hematologic and gastrointestinal toxicities1
  • Overall, seven deaths (4.7%) occurred in the experimental arm, including two due to pneumonia, one due to cardiac arrest, and four post-transplant. In the control arm, , while five deaths (8%) occurred in the control arm, including three due to septic shock, one due to pulmonary hemorrhage, and one due to multi-organ failure1

 

“A chemo-free approach should be the new standard for adult Ph+ ALL”

Dr. Sabina Chiaretti
Sapienza University,
Rome, Italy

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