Nelarabine-combined chemotherapy improves outcome of T-cell acute lymphoblastic leukemia but shows more severe neurotoxicity: JALSG T-ALL213-O

Abstract

We investigated the effectiveness and safety of nelarabine (NEL)-combined chemotherapy for newly diagnosed adult T-cell acute lymphoblastic leukemia (T-ALL) patients. We conducted a phase II trial, T-ALL213-O, where adult T-ALL patients aged 25 to 64 were treated by a regimen based on that used in our previous study, ALL202-O. The main modifications from ALL202-O to T-ALL213-O were as follows: (1) NEL-combined chemotherapy, instead of consolidation (C)1, was used for non-complete remission (CR) patients after induction therapy (IND)1 as IND2; (2) NEL treatments were inserted into C3 and C5 on day 29. Twenty-four patients were analyzed. Ten patients did not receive NEL treatment due to therapy termination prior to C3. Three-year event-free survival (EFS) was 70%, with 52% as the lower limit of its 90% confidence interval, which exceeded the threshold of 25%; thus, the study treatment was considered effective. The CR rates by IND1, IND2, and both were 75%, 100%, and 88%, respectively. The 5-year EFS and 5-year overall survival rates were 66% and 70%, respectively, with median follow-ups of 7.7 and 7.8 years. The addition of NEL improved the CR rate but not survival, compared with T-ALL patients in ALL202-O. Severe neuropathy after NEL administration was observed at a high frequency. Seven (50%) of 14 patients treated with NEL showed grade 3 peripheral neuropathy and/or gait disturbance. The neurotoxicity was considered stronger than that previously reported. Combination therapy of NEL at this dose and intensive multidrug chemotherapy is associated with a high risk of severe neurotoxicity (JALSG T-ALL213-O, UMIN000010642).

Keywords: T‐ALL; acute lymphoblastic leukemia; clinical trial; nelarabine; neuropathy.

FIGURE 1

Consolidated Standards of Reporting Trials (CONSORT) diagram for the flow of patients through the study.

FIGURE 2

Survival analysis of T‐ALL213‐O. (A) Event‐free survival (EFS) curve of T‐ALL213‐O. Stem cell transplantation (SCT) cases were not treated as censored cases. The 90% CI is demonstrated as a gray area. The dashed line indicates threshold EFS. (B) OS curve of T‐ALL213‐O. SCT cases were not treated as censored cases.

FIGURE 3

Comparison of survival between T‐ALL213‐O and T‐ALL202‐O. Event‐free survival (EFS) (A) and OS (B) were compared between T‐ALL213‐O (red line) and T‐ALL202‐O (blue line). Stem cell transplantation (SCT) cases were not treated as censored cases.