The Children’s Oncology Group AALL0434 protocol (ClinicalTrials.gov Identifier: NCT00408005), which consists of Capizzi-based methotrexate/pegaspargase (C-MTX), appears to be safe and effective for newly diagnosed patients with T-cell lymphoblastic lymphoma (T-LL), according to research published in the Journal of Clinical Oncology.
It was previously unestablished whether MTX with leucovorin rescue (HD-MTX) or C-MTX is superior for T-LL treatment, both of which are often used in this setting. For this phase 3 trial, researchers evaluated whether C-MTX yields superior efficacy and safety outcomes in pediatric patients with T-LL, and whether adding nelarabine, a prodrug of ara-G, is superior among high-risk patients.
A total of 299 patients aged 1 to 31 years were enrolled; 282 were evaluable for induction and 205 were evaluable for post-induction therapy. Participants were either assigned to received C-MTX treatment alone (arm A) or C-MTX with nelarabine (arm B). Of the 84 standard-risk patients, 82 participants were assigned to arm A; 64 completed therapy. The 2 patients who failed induction therapy were assigned to arm B — both of whom completed treatment. Of the 121 high-risk patients, 61 were assigned to arm A (51 completed therapy) and 60 were assigned to arm B (46 completed therapy).
Among the 282 patients evaluable for induction, the mean age was 11.2 years, 69.2% of patients were male, and 55% of patients had Murphy stage 2 or 3 disease. Nearly half (47.5%) of patients had pretreatment minimal detectable disease (MDD) of less than 0.1%.
The 4-year event-free survival and overall survival rates of the group were 84.7% and 89.0%, respectively. From induction termination, the 4-year disease-free survival (DFS) rate was 85.9%. Risk-group assignment and treatment regimen did not predict DFS, and adding nelabarine did not improve outcomes among high-risk patients.
Among 61 patients in arm A, the most common adverse event (AE) was grade 3 to 4 infection (25 patients), although the infection rate between groups was not significant (P =.857). Toxicities including peripheral motor neuropathy and peripheral sensory neuropathy (both grade 1-2) were significantly more common among patients in arm B (P =.033 and P =.005, respectively).
“[T]he observed toxicities of this treatment regimen were relatively low, with 1 benign tumor to date and a nonrelapse mortality rate of only 1.8%. The outstanding outcomes achieved from this trial provide the basis on which future therapies can be built,” the authors concluded.
Hayashi RJ, Winter SS, Dunsmore KP, et al. Successful outcomes of newly diagnosed T lymphoblastic lymphoma: results from Children’s Oncology Group AALL0434 [published online June 17, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.00531