One cycle of nelarabine given after induction is well tolerated but does not improve outcome in adults with T‐cell precursor acute lymphoblastic leukemia: Outcome data from the UKALL14 randomized‐controlled trial

Abstract UKALL14 (NCT01085617) T‐cell arm was a phase 3, randomized‐controlled trial. Adults aged 25–65 years were randomized 1:1 at entry to receive standard of care (SOC) or SOC + nelarabine 1.5 g/m 2 (Days 1, 3, and 5) to be administered following second induction. The primary end‐point was event‐free survival (EFS). From 2011 to 2018, 143 patients were randomly assigned to SOC ( N  = 75) or SOC + nelarabine ( N  = 68). There was no significant difference in EFS between the treatment groups; HR 0.86 (95% CI 0.52–1.43) P = 0.57, EFS: 58.2% SOC versus 62.7% SOC + nelarabine. The severe adverse events and nonrelapse mortality rates did not differ between the arms; in particular, there was no difference in grade 3–4 neurotoxicity. The 3‐year cumulative incidence of relapse was 31% in the SOC arm versus 28.9% in the SOC+ nelarabine arm. Forty of 44 relapses (90.9%) occurred within 2 years of randomization; the median survival postrelapse was 5.7 months, with no difference by arm. Diagnostic samples were analyzed for level of differentiation arrest by analysis of the TCRg locus to detect the most immature cases through absence of biallelic TCRg deletion (ABD). There was a trend toward more relapses with ABD (37.3%) versus no ABD (19.5%), P = 0.066. Diagnostic samples ( N  = 133) were analyzed for mutations in NOTCH1, FBXW7, NRAS, KRAS, and PTEN , with no significant differences in CR rates or survival in patients with wild‐type (WT) NOTCH1 or FBXW7 . The 12 patients with NRAS mutations had significantly inferior CR and EFS compared to patients with wild‐type NRAS .