Kimberly P. Dunsmore
The addition of nelarabine to standard chemotherapy prolonged DFS among children and young adults newly diagnosed with T-cell acute lymphoblastic leukemia and should become a standard of care for this population, according to results of a phase 3 trial scheduled for presentation at the ASCO Annual Meeting.
Nelarabine (Arranon, Novartis) is a T-cell specific agent approved for patients who have failed at least two prior chemotherapy regimens.
“This is the largest clinical trial for children and young adults with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma,” Kimberly P. Dunsmore, MD, chair of pediatrics and professor at Virginia Tech Carilion School of Medicine and Research Institute, said during a press conference. “This is the best ever survival data with T-cell acute lymphoblastic leukemia.”
Approximately 80% of patients with T-cell ALL live at least 4 years after treatment, according to Dunsmore, who added in a press release that “we felt we could and must do better.”
The study included 1,895 patients aged 1 to 30 years newly diagnosed with T-cell ALL (94%) or T-cell lymphoblastic lymphoma (6%), all of whom received the Children’s Oncology Group augmented Berlin-Frankfurt-Munster chemotherapy regimen.
Researchers randomly assigned patients based on a 2 x 2 pseudo-factorial to receive escalating-dose methotrexate without leucovorin rescue plus pegaspargase (CMTX) or high-dose methotrexate plus leucovorin rescue. Patients with an intermediate or high risk for recurrence underwent second randomization to 650 mg/m2 nelarabine daily or no nelarabine for six 5-day courses.
Patients with intermediate- or high-risk T-cell ALL also received 1,200 cGy prophylactic or 1,800 cGy therapeutic cranial irradiation.
At 4 years, OS was 90.2% and DFS was 84.1% among all patients.
Among patients with T-cell ALL with increased risk for recurrence, 88.9% who received nelarabine (n = 323) remained disease free at 4 years compared with 83.3% of patients not treated with nelarabine (n = 336; P = .0332).
Among patients with T-cell ALL who received CMTX, 4-year DFS was 92.2% for those who receive nelarabine (n = 147) compared with 89.8% for those who did not receive nelarabine (n = 151). Among those who received high-dose methotrexate, 4-year DFS rates were 86.2% with nelarabine (n = 176) compared with 78% without nelarabine (n = 185; P = .024).
Thus, unlike previous trials, those who received escalating methotrexate achieved longer DFS than those who receiving high-dose methotrexate (89.8% vs. 78%).
Forty-three patients with T-cell ALL with induction failure were nonrandomly assigned to high-dose methotrexate plus nelarabine. For this group, 4-year DFS reached 54.8%, which represented an improvement from historical data that indicate only about 20% of patients with T-cell ALL who do not achieve remission survive another 3 years, according to the researchers.
Nelarabine did not appear to improve outcomes for patients with T-cell lymphoblastic lymphoma, for whom 4-year DFS was 85% among patients who receive nelarabine (n = 60) and 89% among those who did not (n = 58).
Overall toxicity and neurotoxicity did not significantly differ among the four arms.
“The next steps are to examine what implications and benefits may accrue when using nelarabine in protocols without cranial irradiation to decrease long-term neurologic side effects,” Dunsmore said. – by Melinda Stevens
Dunsmore KP, et al. Abstract 10500. Scheduled for presentation at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Dunsmore reports leadership roles with, as well as family members employed by, TypeZero, and travel accommodations and expenses for family members from Novo Nordisk and Tandem Diabetes Care. Please see the abstract for all other authors’ relevant financial disclosures.