Response-based Therapy Intensification Improves Survival in Adult ALL
Early response–based treatment intensification with allo-SCT improved OS among adult patients with early thymic precursor T cell ALL.
Early response–based treatment intensification with allogeneic stem cell transplant (allo-SCT) improved overall survival (OS) among adult patients with early thymic precursor (ETP) T cell acute lymphoblastic leukemia (ALL), according to a study published in the Journal of Clinical Oncology.1
Chemotherapy resistance is a negative prognostic indicator among children with ETP-ALL, but can be abrogated by using early response–based treatment intensification strategies. This study aimed to determine if the same strategy could improve outcomes among adults with this disease.
This retrospective analysis evaluated clinicobiologic, genetic, and survival data from a cohort of 213 adult patients with T-ALL treated in the phase 2 and 3 GRAALL-2003 and -2005 studies (ClinicalTrials.gov Identifiers: NCT00222027, NCT00327678). In these studies, patients underwent therapy intensification with allo-SCT if early treatment resistance occurred.
Immunophenotypic analysis identified that 22.1% of patients had ETP-ALL, which showed a distinct gene expression signature compared with non-ETP T-ALL. Patients with ETP were more likely to be female and of older age and to have lower white blood cell counts at diagnosis.
ETP was also associated with higher rates of MLLT10 translocation and lower rates of TLX1 rearrangement. The mutational frequency was also higher among patient with ETP (89.2% of patients) compared with non-ETP T-ALL (63.7% of patients).
Early bone marrow chemotherapy resistance occurred in 87% of patients with ETP, but those treated by the GRAALL protocol of early treatment intensification with allo-SCT had a similar OS as patients with non-ETP T-ALL.
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The GRAALL protocol resulted in 5-year OS rates of 59.6% (95% CI, 44.2-72.0%) in ETP compared with 66.5% (95% CI, 58.7-73.2%; P = .33) in non-ETP T-ALL. This was in part driven by allo-SCT, which trended toward improved survival among patients with ETP (hazard ratio [HR], 0.36; P = .07) but not non-ETP T-ALL (HR, 0.70; P = .30).
According to the authors, these data suggest “that transplantation conferred survival benefit in high-risk patients with ETP-ALL who had already received augmented induction regimens suggests that allo-SCT is a key component of therapy escalation.”
- Bond J, Graux C, Lhermitte L, et al. Early response-based therapy stratification improves survival in adult early thymic precursor acute lymphoblastic leukemia: a Group for Research on Adult Acute Lymphoblastic Leukemia Study. J Clin Oncol. 2017 Jun 12. doi: 10.1200/JCO.2016.71.8595 [Epub ahead of print]