(ChemotherapyAdvisor) –Nelarabine added to an intensive modified Berlin-Frankfurt-Münster (BFM) 86-based chemotherapy regimen produced “encouraging results” and was well tolerated in children newly diagnosed with high-risk T-cell acute lymphoblastic leukemia (T-ALL), according to results of a study published online June 25 in the Journal of Clinical Oncology.

These results were demonstrated particularly in patients with a slow early response, “who have historically fared poorly,” noted Kimberly Dunsmore, MD, of the Children’s Oncology Group and University of Virginia Health Sciences Center, Charlottesville, VA; and colleagues.

“Overall, 75% to 80% of children with T-ALL are cured with contemporary chemotherapy regimens,” they write. “However, the salvage rate is extremely poor for patients who relapse. Thus, to improve survival for children with T-ALL, it is essential to identify effective agents that can be incorporated into first-line chemotherapy regimens. The most powerful predictor of poor outcome in T-ALL is a poor early chemotherapy response….”

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The Children’s Oncology Group pilot study was conducted in two stages. In stage one, 8 patients with a slow early response by prednisone poor response (PPR; ≥1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus 6 courses of nelarabine 400 mg/m2 once per day; 4 patients with slow early response by high minimal residual disease (MRD; ≥1% at day 36 of induction) received chemotherapy plus 5 courses of nelarabine and 16 patients with a rapid early response received chemotherapy without nelarabine.

In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m2 once per day (10 patients with slow early response [1 by MRD, 9 by PPR]) or 400 mg/m2 once per day (38 patients with rapid early response and 12 with slow early response [3 by MRD, 9 by PPR]).

Five-year event-free survival rates were 73% for 11 stage one slow early response patients and 67% for 22 stage two slow early response patients treated with nelarabine vs 69% for 16 stage one rapid early response patients treated without nelarabine and 74% for 38 stage two rapid early response patients treated with nelarabine.

For all patients receiving nelarabine (n=70), 5-year event-free survival was 73% vs 69% for those treated without nelarabine (n=16). The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine, 42%, vs 81% in those who did not receive nelarabine.

Based on these results, the Children’s Oncology Group is currently conducting a randomized phase 3 trial of chemotherapy with and without nelarabine 650 mg/m2 in children, adolescents, and young adults with T-ALL. Given “significant concerns about the potential for neurotoxicity,” each is being carefully monitored for this adverse effect, they reported.