Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma

Am J Hematol. 2018 Jan;93(1):91-99. doi: 10.1002/ajh.24947. Epub 2017 Nov 3.

Abstract

Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arabinonucleosides / administration & dosage
  • Arabinonucleosides / pharmacology
  • Arabinonucleosides / therapeutic use*
  • Female
  • Humans
  • Immunophenotyping / methods*
  • Male
  • Middle Aged
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Survival Analysis
  • Young Adult

Substances

  • Arabinonucleosides
  • nelarabine