A brand new research suggests {that a} therapy mixture with out conventional chemotherapy ought to turn out to be the brand new commonplace for grownup sufferers newly recognized with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL).
Outcomes from the part 3 GIMEMA ALL2820 trial (NCT04722848), offered in a press briefing on the 2025 American Society of Hematology (ASH) Annual Assembly and Exposition, confirmed that the mix of Iclusig (ponatinib) and Blincyto (blinatumomab) led to higher outcomes in contrast with the usual method of Gleevec (imatinib) plus chemotherapy.
Particularly, findings, which have been discovered to be statistically vital, confirmed {that a} full hematologic response (CHR) was noticed in 94.3% of sufferers within the Iclusig plus Blincyto arm in contrast with 79.4% of these handled with Gleevec plus chemotherapy; 2.5% vs. 10.2% of sufferers died, 0% vs. 1.3% had refractory illness, and a pair of.8% vs. 8.9% of sufferers have been off therapy (P = .004).
Within the Iclusig plus Blincyto group of sufferers, no molecular responses have been reported in 53.2% on the finish of their induction therapy vs. 29.1% after 2 cycles of Blincyto, a whole molecular response (CMR) in 30.4% vs. 51.9%, and constructive non-quantifiable (PNQ) in 16.5% vs. 19.0%. The general molecular response was 46.8% vs. 70.9%.
Within the Gleevec-plus-chemotherapy group, there was no molecular response in 56.4% of sufferers on the finish of induction vs. 51.3% after 4 to six cycles of chemotherapy, relying 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 general molecular responses.
Outcomes have been in contrast with earlier findings from the D-ALBA trial (NCT02744768; n = 63) and confirmed that within the experimental arm, the general molecular response was 26.9% on the finish of induction vs. 52.4% after 2 cycles of Blincyto remedy.
At a median follow-up of 23.4 months, the event-free survival (EFS) fee within the Iclusig plus Blincyto arm was 90% (vary, 86%-95%) in contrast with 74% (vary, 65%-85%) within the management arm (P = .0015). The general survival (OS) was 94% (vary, 91%-98%) within the Iclusig plus Blincyto arm vs. 77% (vary, 66%-91%) within the management arm, and 97% (vary, 90%-100%) crossed over.
“A chemotherapy-free method needs to be the brand new commonplace for Ph ALL,” Dr. Sabina Chiaretti from the Sapienza College of Rome in Italy, stated through the presentation. “The primary outcomes of the part 3 GIMEMA ALL2820 trial present for the primary time, in head-to-head comparability, a big benefit of a chemotherapy-free, focused immunotherapeutic-based method over a tyrosine kinase inhibitor and chemotherapy technique, with a better CHR and minimal residual illness response, fewer deaths, and improved EFS and OS.”
Sufferers have been randomly assigned 2:1 to both the experimental arm (n = 158) or the management arm (n = 78). Within the experimental arm, if sufferers have been between 18 and 65 years previous they got Iclusig at 45 mg/day for the primary 22 days, adopted by 30 mg per day till day 70, and adopted by 2 cycles of Blincyto plus Iclusig; if sufferers have been 65 years or older, they got 30 mg of Iclusig per day till day 70 adopted by 2 cycles of Blincyto and Iclusig remedy.
Within the management arm, if sufferers have been between 18 and 65 years previous they got chemotherapy plus Gleevec for 3 cycles till day 70, adopted by cycles 4 to six of Gleevec; if sufferers have been 65 years previous or older they got delicate chemotherapy plus Gleevec for 3 cycles till day 7, adopted by cycle 4 of Gleevec if there was no CHR or MRD response sufferers may cross over to the experimental arm.
Dr. Chiaretti famous that ongoing research will additional study this therapy, specializing in detailed molecular monitoring and affected person high quality of life.
Reference
Chiaretti S, Di Trani M, Skert C, et al. First outcomes of the Part III GIMEMA ALL2820 trial evaluating ponatinib plus blinatumomab to imatinib and chemotherapy for newly recognized grownup Ph+ acute lymphoblastic leukemia sufferers. Blood. 2025;146(suppl 1):439. doi.10.1182/blood-2025-439
