Addition of Nelarabine Improves Outcomes in Pediatric/Young Adult Patients With T-ALL

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When treated with nelarabine, intensive L-asparaginase, and protracted intrathecal therapy, patients aged 25 years and younger with T-cell acute lymphoblastic leukemia (T-ALL) had encouraging outcomes with acceptable toxicities.¹

Despite limited cranial radiotherapy and hematopoietic stem-cell transplantation (HSCT) use, the median follow-up in the study was 5.2 years (IQR, 3.6-6.7) and the 3-year event-free survival (EFS) improved with a rate of 86.4% (95% CI, 82.3-89·7%).

These data come from a nationwide, multicenter, phase 2 trial, which enrolled pediatric and young adult patients with newly diagnosed T-ALL. The trial stratified patients into standard-risk, high-risk, and very-high-risk groups according to prednisolone response, central nervous system (CNS) status, and end-of-consolidation minimal residual disease.1

In the study, patients deemed high-risk or very-high risk received nelarabine at a dose of 650 mg/m2 per day for 5 days. All patients were given an identical therapy schedule, which included the pre-phase prednisolone monotherapy with dexamethasone at 10 mg/m2 per day, for 3 weeks for patients 10 years of age or younger, or for 2 weeks including a 7-day off interval for patients 10 years and older. This continued until the measurement of end-of-consolidation minimal residual disease (MRD).

The study assessed the primary end points of 3-year event-free survival (FES) for the entire cohort and the proportion of patients with disappearance of MRD between randomly assigned groups A and B in the very high-risk group. Secondary end points evaluated were overall survival (OS), remission induction rate, and occurrence of adverse events (AEs).

A total of 349 patients were enrolled between December 1, 2011, and November 30, 2017, with a median age of 9 years (interquartile range [IQR], 6-13), 238 (68%) were male, and 28 (8%) patients had CNS3 status. There were 168 (48%) patients stratified as standard-risk, 103 (30%) as high-risk, 39 (11%) as very high-risk, and 39 (11%) as no risk.

Findings revealed that the composite complete remission rate, which was complete remission plus complete remission in suppression, after remission induction therapy was 89% among patients. Thirty-five (10%) patients underwent HSCT. The 3-year OS rate was 91.3% (87.7-93.8%).

In group A, the proportion of MRD disappearance was 0.86 (95% CI, 0.57-0.98) and in group B, it was 0.50. Peripheral motor neuropathy that was grade 3 was reported in 11 (3%) patients and sensory neuropathy was observed in 6 (2%) patients.

Safety findings also showed that the most common grade 3 or worse AE was febrile neutropenia, which was seen in 84% of patients. Three patients died due to treatment-related toxicity, including sepsis, gastric perforation, or intracranial hemorrhage during remission induction.

Nelarabine was only used in the high-risk and very high-risk groups. Experts believe that adding nelarabine to the standard risk protocol might further improve the results in the standard risk group moving forward. Additionally, as this study focused on patients aged 25 years and younger, future trials may evaluate the combination while raising the upper age limit of those enrolled.

REFERENCE:

Sato A, Hatta Y, Imai C, et al. Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group [published correction appears in Lancet Haematol. 2023 Jun;10(6):e399]. Lancet Haematol. 2023;10(6):e419-e432. doi:10.1016/S2352-3026(23)00072-8