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

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

Dr. Sabina Chiaretti
Sapienza University,
Rome, Italy