A multicenter total therapy strategy for de novo adult Philadelphia chromosome positive acute lymphoblastic leukemia patients. Final results of the GIMEMA LAL1509 protocol

• Published in: Haematologica (Roma) 2021-07, Vol.106 (7), p.1828-1838
• Main Authors: Chiaretti, Sabina, Ansuinelli, Michela, Vitale, Antonella, Elia, Loredana, Matarazzo, Mabel, Piciocchi, Alfonso, Fazi, Paola, Di Raimondo, Francesco, Santoro, Lidia, Fabbiano, Francesco, Califano, Catello, Martinelli, Giovanni, Ronco, Francesca, Ferrara, Felicetto, Cascavilla, Nicola, Bigazzi, Catia, Tedeschi, Alessandra, Sica, Simona, Di Renzo, Nicola, Melpignano, Angela, Beltrami, Germana, Vignetti, Marco, Foa, Robin
• Format: Article
• Language: English
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2020.260935

The GIMEMA LAL1509 protocol, designed for adult (≥18-60 years) de novo Ph+ acute lymphoblastic leukemia patients, was based on a dasatinib plus steroids induction - with central nervous system prophylaxis - followed by dasatinib alone in patients in complete molecular response or chemotherapy and/or allogeneic transplantation in patients not reaching a complete molecular response. Sixty patients (median age 41.9 years) were enrolled: 33 were p190+, 18 p210+ and 9 p190/p210+. At the end of induction (day +85), 58 patients (97%) achieved a complete hematologic remission. No deaths in induction were recorded. Eleven patients (18.3%) obtained a complete molecular response. Among non-complete molecular responders (n=47), 22 underwent an allogeneic transplant. Seventeen hematologic relapses occurred (median 7 months, range 3-40.1), 13 during consolidation and 4 post-transplant. ABL1 mutations (5 T315I, 3 V299L, 1 E281K and 1 G254E) were found in 10/13 relapsed cases. With a median follow-up of 57.4 months (range: 4.2-75.6), overall survival and disease-free survival are 56.3% and 47.2%. A better diseasefree survival was observed in patients who obtained a molecular response at day +85 compared to cases who did not. The presence of additional copy number aberrations - IKZF1 plus CDKN2A/B and/or PAX5 deletions - was the most important unfavorable prognostic factor on overall and disease-free survival (p=0.005 and p=0.0008). This study shows that in adult Ph+ ALL long-term survivals can be achieved with a total-therapy strategy based on a chemo-free induction and, in complete molecular responders, also without further systemic chemotherapy. Finally, the screening of additional copy number aberrations should be included in the diagnostic work-up. EudraCT 2010-019119-39.