Share this article on:

First-Line Nelarabine Improves Survival in T-Cell Cancers

Fuerst, Mark L.

doi: 10.1097/01.COT.0000542459.92428.9f
News

CHICAGO—First-line therapy with nelarabine plus chemotherapy improves disease-free survival (DFS) for children and young adults with newly diagnosed T-cell cancers.

A randomized phase III trial performed by the Children's Oncology Group (COG) found 90 percent of children and young adults with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL) were alive 4 years after starting treatment regimens on this trial, and 84 percent were cancer-free.

“This is the best ever survival data with T-ALL. Patients who received nelarabine had better survival and fewer CNS relapses,” said lead author Kimberly Dunsmore, MD, Professor, Virginia Tech Carilion School of Medicine in Roanoke, at a press briefing before the 2018 ASCO Annual Meeting (Abstract 10500).

The addition of nelarabine to standard chemotherapy provided further benefit for the group of patients who were at moderate or high risk of T-ALL recurrence: at 4 years, 89 percent of those who received nelarabine were leukemia-free versus 83 percent of those who did not.

T-ALL/T-LL affects one out of every six children and young adults who are diagnosed with ALL. “Despite very intense and complex chemotherapy, 20 percent of children and adolescents enrolled in COG T-ALL trials in 2000-2005 did not survive. New drugs were needed to improve survival rates for T-ALL/LL,” said Dunsmore, adding that nelarabine was known to be a T-cell specific drug with success in relapsed patients.

“Historically, about 80 percent of people live at least 4 years after being treated for their disease, but we felt we could and must do better. Our trial shows that we could further increase survival rates by about 10 percent, which is very encouraging.”

The COG trial enrolled 1,895 patients, ages 1-30 years, from 2007 to 2014 with either T-ALL (94% of trial participants) or T-LL (6% of participants), making it the largest randomized clinical trial ever performed in these diseases.

Patients were randomized to either escalating doses of methotrexate with or without six courses of nelarabine, 5-day courses at 650 mg/m2 per day, or high-dose methotrexate with or without six courses of nelarabine.

All patients receiving the standard, complex, multi-drug augmented Berlin-Frankfurt-Munster chemotherapy. Those patients with T-cell ALL also received either prophylactic or therapeutic cranial irradiation to prevent or treat brain metastases.

Nelarabine was approved in 2005 by the FDA for the treatment of people with T-ALL and T-LL that had progressed after at least two chemotherapy regimens.

Back to Top | Article Outline

Key Findings

Overall, 90.2 percent of patients treated lived at least 4 years, and 84.3 percent had no sign of cancer at 4 years. In the group of patients with T-ALL who had increased risk of recurrence, 88.9 percent of those who received nelarabine were leukemia-free at 4 years compared to 83.3 percent of those not treated with nelarabine. While patients with T-LL did not benefit from the addition of nelarabine, more than 85 percent lived for 4 years without signs of disease.

Contrary to results from previous, smaller trials, patients with T-ALL who received escalating doses of methotrexate did better than those who received high-dose methotrexate (4-year disease-free survival with escalating dose was 89.8% vs. 78% with high-dose methotrexate). Among T-ALL patients randomly assigned to receive both nelarabine and escalating doses of methotrexate, 4-year DFS was 92.2 percent.

Patients who did not achieve remission following the initial induction phase of chemotherapy were assigned to receive high-dose methotrexate and nelarabine; 54.8 percent survived 4 years without signs of the disease. This is a significant improvement, as historically only about 20 percent of patients with T-ALL who do not achieve remission live another 3 years, Dunsmore said.

Overall, toxicity and neurotoxicity were acceptable and not significantly different between all four arms. There was no difference in peripheral neurotoxicities between the arms, according to Dunsmore. “There was only 8 percent grade 3/4 peripheral motor or sensory neuropathy.” Patients receiving nelarabine had fewer CNS relapses.

“Nelarabine improved outcome for randomized T-ALL patients. The best treatment arm was escalating doses of methotrexate plus nelarabine, with a 4-year DFS of 91 percent,” said Dunsmore. “Patients who didn't achieve induction remission had a 54 percent survival at 4 years, more than double past survival rates. T-LL didn't receive a benefit from nelarabine, but still had very good survival of 85 percent at 4 years.”

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.

“As oncologists, we are constantly striving for better care and outcomes for our patients, even in cancers where survival rates are relatively high compared with others,” commented ASCO President Bruce E. Johnson, MD, Professor of Medicine at Harvard Medical School, Boston. “We now know it's possible to significantly boost survival in children and young adults with rare forms of leukemia and lymphoma, without introducing additional harsh side effects that can impair their quality of life.

“Nelarabine increased DFS by about 10 percent with no particular increase in side effects,” he added. “This drug has been approved for relapsed/refractory disease. Now it may move to the upfront setting and improve outcomes.”

Mark L. Fuerst is a contributing writer.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Home  Clinical Resource Center
Current Issue       Search OT
Archives Get OT Enews
Blogs Email us!