A New Option Without Traditional Chemotherapy for Ph+ ALL

A new study suggests that a treatment combination without traditional chemotherapy should become the new standard for adult patients newly diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL).

Results from the phase 3 GIMEMA ALL2820 trial (NCT04722848), presented in a press briefing at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, showed that the combination of Iclusig (ponatinib) and Blincyto (blinatumomab) led to better outcomes compared with the standard approach of Gleevec (imatinib) plus chemotherapy.

Specifically, findings, which were found to be statistically significant, showed that a complete hematologic response (CHR) was observed in 94.3% of patients in the Iclusig plus Blincyto arm compared with 79.4% of those treated with Gleevec plus chemotherapy; 2.5% vs. 10.2% of patients died, 0% vs. 1.3% had refractory disease, and 2.8% vs. 8.9% of patients were off treatment (P = .004).

In the Iclusig plus Blincyto group of patients, no molecular responses were reported in 53.2% at the end of their induction treatment vs. 29.1% after 2 cycles of Blincyto, a complete molecular response (CMR) in 30.4% vs. 51.9%, and positive non-quantifiable (PNQ) in 16.5% vs. 19.0%. The overall molecular response was 46.8% vs. 70.9%.

In the Gleevec-plus-chemotherapy group, there was no molecular response in 56.4% of patients at the end of induction vs. 51.3% after 4 to 6 cycles of chemotherapy, depending on age; 35.9% vs. 37.2% had a CMR, 7.7% vs. 11.5% had a PNQ, and 43.6% vs. 48.7% had overall molecular responses.

Results were compared with previous findings from the D-ALBA trial (NCT02744768; n = 63) and showed that in the experimental arm, the overall molecular response was 26.9% at the end of induction vs. 52.4% after 2 cycles of Blincyto therapy.

At a median follow-up of 23.4 months, the event-free survival (EFS) rate in the Iclusig plus Blincyto arm was 90% (range, 86%-95%) compared with 74% (range, 65%-85%) in the control arm (P = .0015). The overall survival (OS) was 94% (range, 91%-98%) in the Iclusig plus Blincyto arm vs. 77% (range, 66%-91%) in the control arm, and 97% (range, 90%-100%) crossed over.

“A chemotherapy-free approach should be the new standard for Ph ALL,” Dr. Sabina Chiaretti from the Sapienza University of Rome in Italy, said during the presentation. “The first results of the phase 3 GIMEMA ALL2820 trial show for the first time, in head-to-head comparison, a significant advantage of a chemotherapy-free, targeted immunotherapeutic-based approach over a tyrosine kinase inhibitor and chemotherapy strategy, with a higher CHR and minimal residual disease response, fewer deaths, and improved EFS and OS.”

Patients were randomly assigned 2:1 to either the experimental arm (n = 158) or the control arm (n = 78). In the experimental arm, if patients were between 18 and 65 years old they were given Iclusig at 45 mg/day for the first 22 days, followed by 30 mg per day until day 70, and followed by 2 cycles of Blincyto plus Iclusig; if patients were 65 years or older, they were given 30 mg of Iclusig per day until day 70 followed by 2 cycles of Blincyto and Iclusig therapy.

In the control arm, if patients were between 18 and 65 years old they were given chemotherapy plus Gleevec for 3 cycles until day 70, followed by cycles 4 to 6 of Gleevec; if patients were 65 years old or older they were given mild chemotherapy plus Gleevec for 3 cycles until day 7, followed by cycle 4 of Gleevec if there was no CHR or MRD response patients could cross over to the experimental arm.

Dr. Chiaretti noted that ongoing studies will further examine this treatment, focusing on detailed molecular monitoring and patient quality of life.

Reference

Chiaretti S, Di Trani M, Skert C, et al. First results of the Phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult Ph+ acute lymphoblastic leukemia patients. Blood. 2025;146(suppl 1):439. doi.10.1182/blood-2025-439