Nelarabine Combination Therapy for Relapsed or Refractory T-cell Acute Lymphoblastic Lymphoma/Leukemia.

Nelarabine, an anti-metabolite prodrug, is approved as monotherapy for children and adults with relapsed and refractory T-cell acute lymphoblastic leukemia and lymphoma (R/R T-ALL/LBL), although it is often used in combination regimens. We sought to understand differences in efficacy and toxicity when nelarabine is administered alone or in combination. We retrospectively analyzed 44 consecutive patients with R/R T-ALL/LBL: 29 were treated with combination therapy, most with cyclophosphamide and etoposide (23, 79%) and 15 with monotherapy. The median age was 19 years (range, 2-69) with 18 children (< 18 years) included. After a median of 1 (range 1-3) cycle of treatment, 24 patients (55%) achieved CR: 62% with combination therapy and 40% with monotherapy (p 0.21). Most responders (21, 88%) pursued allogeneic stem cell transplant (alloSCT). Overall survival (OS) was 12.8 months (CI 95% 6.93-not reached) in the entire cohort and was higher in the combination therapy vs. monotherapy group (24-month OS 53% vs. 8%, p 0.003). The rate of neurotoxicity was similar between groups (27% vs. 17%, p 0.46) while grade III/IV anemia and thrombocytopenia were more frequent in the combination group (76 vs. 20%, p<0.001 and 66% vs. 27%, p 0.014, respectively). In a multivariable analysis, nelarabine combination therapy and alloSCT post nelarabine were associated with improved OS (HR 0.41, p 0.04 and HR 0.25, p 0.008). In conclusion, compared to monotherapy, nelarabine combination therapy was well tolerated and associated with improved survival in pediatric and adult patients with R/R T-ALL/LBL.