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

Abstract

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.

• Authors: Sabina Chiaretti, Michela Ansuinelli, Antonella Vitale, Loredana Elia, Mabel Matarazzo, Alfonso Piciocchi, Paola Fazi, Francesco Di Raimondo, Lidia Santoro, Francesco Fabbiano, Catello Califano, Giovanni Martinelli, Francesca Ronco, Felicetto Ferrara, Nicola Cascavilla, Catia Bigazzi, Alessandra Tedeschi, Simona Sica, Nicola Di Renzo, Angela Melpignano, Germana Beltrami, Marco Vignetti, Robin Foa
• Journal: Haematologica (Haematologica) Vol. 106 Issue 7 Pg. 1828-1838 (07 01 2021) ISSN: 1592-8721 [Electronic] Italy
• PMID: 33538150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fusion Proteins, bcr-abl
• Dasatinib

Topics

• Adult
• Dasatinib (therapeutic use)
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Multicenter Studies as Topic
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (diagnosis, genetics, therapy)
• Remission Induction