Background. BCR/ABL1-like acute lymphoblastic leukemia (Phlike ALL) is a heterogeneous entity with a transcriptional profile similar to that of true Ph-positive ALL. Ph-like ALL is associated with a poor outcome and new approaches are needed. Methods. Based on in vitro (1) and in vivo data (2), the BALLik trial is an interventional, phase II study for newly diagnosed Ph-like ALL patients (pts) - identified on the basis of the BCR/ABL1-like predictor (1) -, aged 18-65 years, which contemplates the combination of the 3rd generation tyrosine kinases inhibitor (TKI) ponatinib to an intensive pediatric- inspired chemotherapy regimen, without asparaginase to avoid excessive organ toxicity. For safety reasons, the trial foresaw a run-in phase with ponatinib at the starting dose of 15 mg daily for the first 5 pts and 30 mg daily for the other pts. Allogeneic transplant after cycle 3 was mandatory. The trial is ending enrollment (samples size, 32 pts). Results. The data hereby presented relate to 24 evaluable pts: 50% were male, median age was 39 yrs, median white blood cells count at diagnosis was 3x109/L (0.7-82x109/L), and CRLF2 expression, usually predictive of an underlying gene rearrangement, was high in 11/27cases (CRLF2HIGH 40.7%). Of the 19 evaluable pts, 8 (32%) held an IKZF1plus profile defined by multiplex ligation-probe dependent amplification. Targeted RNA sequencing identified in 7/19 cases a fusion transcript (4 ABL class, 1 JAK2 and 2 ZCCHC7 rearrangements). Cytogenetics/ FISH analysis is ongoing. All pts were NGS-screened for a IG/TR gene marker and minimal residual disease (MRD) monitoring. Currently, 22 pts have completed the induction phase (cycles 1 and 2). Complete remission (CR) was achieved by 18/22 pts (81.8%), while 4 proved refractory: 2 of the latter were CRLF2HIGH (1 with a concomitant IKZF1plus profile), 1 was JAK2- and 1 ZCCHC7-rearranged. There were no deaths in induction. After cycle 3 (TP2, primary endpoint), an IG/TR MRD negativity was found in 11/16 pts (69%), a value a little higher than in historical controls. So far, 8 pts have been allografted. Preliminary overall, disease-free- and event-free survival rates are promising. One pt died due to infection and another pt relapsed within the first 12 months. Conclusions. The preliminary results of this frontline trial for Phlike ALL show that a combined approach incorporating ponatinib is feasible with improved MRD negativity. Updated findings will be presented at the congress.
Ponatinib Plus Chemotherapy as Frontline Treatment for BCR/ABL1-Like Acute Lymphoblastic Leukemia Patients. Preliminary Results of the GIMEMA ALL2922-BALLIK Trial / Chiaretti, S., Kaiser, F., Ansuinelli, M., Cardinali, D., Bellomarino, V., Mulè, A., Fucci, L., Leoncin, M., Annunziata, M., Cerrano, M., Della Starza, I., Di Trani, M., La Starza, R., De Propris, M.S., Piciocchi, A., Messina, M., Arena, V., Foà, R.. - (2025). (SIE 2025 Congress Milano ).
Ponatinib Plus Chemotherapy as Frontline Treatment for BCR/ABL1-Like Acute Lymphoblastic Leukemia Patients. Preliminary Results of the GIMEMA ALL2922-BALLIK Trial
Chiaretti S;Kaiser F;Ansuinelli M;Cardinali D;Bellomarino V;Fucci L;Della Starza I;Di Trani M;La Starza R;De Propris MS;Piciocchi A;Messina M;Foà R
2025
Abstract
Background. BCR/ABL1-like acute lymphoblastic leukemia (Phlike ALL) is a heterogeneous entity with a transcriptional profile similar to that of true Ph-positive ALL. Ph-like ALL is associated with a poor outcome and new approaches are needed. Methods. Based on in vitro (1) and in vivo data (2), the BALLik trial is an interventional, phase II study for newly diagnosed Ph-like ALL patients (pts) - identified on the basis of the BCR/ABL1-like predictor (1) -, aged 18-65 years, which contemplates the combination of the 3rd generation tyrosine kinases inhibitor (TKI) ponatinib to an intensive pediatric- inspired chemotherapy regimen, without asparaginase to avoid excessive organ toxicity. For safety reasons, the trial foresaw a run-in phase with ponatinib at the starting dose of 15 mg daily for the first 5 pts and 30 mg daily for the other pts. Allogeneic transplant after cycle 3 was mandatory. The trial is ending enrollment (samples size, 32 pts). Results. The data hereby presented relate to 24 evaluable pts: 50% were male, median age was 39 yrs, median white blood cells count at diagnosis was 3x109/L (0.7-82x109/L), and CRLF2 expression, usually predictive of an underlying gene rearrangement, was high in 11/27cases (CRLF2HIGH 40.7%). Of the 19 evaluable pts, 8 (32%) held an IKZF1plus profile defined by multiplex ligation-probe dependent amplification. Targeted RNA sequencing identified in 7/19 cases a fusion transcript (4 ABL class, 1 JAK2 and 2 ZCCHC7 rearrangements). Cytogenetics/ FISH analysis is ongoing. All pts were NGS-screened for a IG/TR gene marker and minimal residual disease (MRD) monitoring. Currently, 22 pts have completed the induction phase (cycles 1 and 2). Complete remission (CR) was achieved by 18/22 pts (81.8%), while 4 proved refractory: 2 of the latter were CRLF2HIGH (1 with a concomitant IKZF1plus profile), 1 was JAK2- and 1 ZCCHC7-rearranged. There were no deaths in induction. After cycle 3 (TP2, primary endpoint), an IG/TR MRD negativity was found in 11/16 pts (69%), a value a little higher than in historical controls. So far, 8 pts have been allografted. Preliminary overall, disease-free- and event-free survival rates are promising. One pt died due to infection and another pt relapsed within the first 12 months. Conclusions. The preliminary results of this frontline trial for Phlike ALL show that a combined approach incorporating ponatinib is feasible with improved MRD negativity. Updated findings will be presented at the congress.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
