Total Therapy GIMEMA LAL 1509 Protocol for De Novo Adult Ph+ ALL Patients: Updated Results and Genetic-Based Prognostic Stratification

Conference Correspondent - ASH 2015 - Leukemia


Preliminary findings of the GIMEMA LAL 1509 total therapy protocol, which evaluated the tyrosine kinase inhibitor dasatinib plus steroids as induction therapy in adult patients with de novo Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) were presented previously.1 At ASH 2015, Chiaretti and colleagues presented the updated results of this trial on overall survival (OS), disease-free survival (DFS), and the impact of genetic-based prognostic stratification.2 In this trial, patients received total therapy with induction therapy of dasatinib (140 mg/day, days 1 and 84) and steroids (administered from day 6 to day 31); patients who achieved a complete molecular response (CMR) with induction therapy continued dasatinib until disease progression, and those in complete hematologic remission (CHR) but not in CMR underwent chemotherapy (clofarabine-cyclophosphamide) and/or an allogeneic transplant.

In the cohort of 60 eligible patients, the p190 fusion product was detected in 33 patients, p210 in 18 patients, and p190/p210 in 9 patients. At a median follow-up of 32.8 months, 38 (63%) patients achieved a blast reduction ?75% after the steroid pretreatment. After the end of induction therapy (day 85), 58 patients were in CHR (97%). A sustained CMR was achieved in 11 (19%) patients, the majority of whom had a p190 fusion transcript. Of the 47 patients who did not achieve a CMR, 16 relapses occurred, 9 of which were in patients with p210 abnormality. Overall, OS at 36 months was 58.3%, and DFS at 30 months was 49%. Moreover, patients who obtained a CMR at day 85 achieved a better DFS compared with those with minimal residual disease (79% vs 44%; P = .05), as did patients who were p190+ compared with p210+ (59% vs 40%; P = .19), indicating the importance of CMR achievement at day 85 and that patients with p210+ disease required a more intense treatment approach. Moreover, patients with IKZF1 plus CDKN2A/B and PAX5 deletions showed a significantly worse DFS (40% vs 65% at 18 months; P = .01) and increased cumulative incidence of relapse (40% vs 14% at 18 months; P = .020) compared with those with IKZF1 deletions alone, which was found to be of prognostic relevance in the p190+ but not the p210+ patient subgroup. Overall, 16 serious adverse events occurred in 10 patients, including infections and gastrointestinal disorders. The updated analysis of the GIMEMA 1509 trial confirmed the efficacy of a chemo-free induction regimen in the majority of adult Ph+ ALL patients.

  1. Chiaretti S, et al. ASH 2014. Abstract 797.
  2. Chiaretti S, et al. ASH 2015. Abstract 81.