A phase III randomized trial, with results being presented in June at the American Society of Clinical Oncology Annual Meeting, found the addition of nelarabine to standard chemotherapy regimen in patients with T-cell malignancies can improve disease-free survival rates.
Adding nelarabine to standard chemotherapy resulted in improved survival among children and young adults with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic leukemia (T-LL), according to research to be presented at the American Society of Clinical Oncology (ASCO) annual meeting, June 1-5, 2018, in Chicago, Illinois.
Nelarabine is already approved for treatment of people with T-ALL and T-LL after failure of 2 or more chemotherapy regimens. This new randomized phase III clinical trial from the Children’s Oncology Group tested the treatment in 1895 patients between the ages of 1 and 30 who were newly diagnosed.
The study found that 90% of the patients were alive 4 years after the start of treatment and 84% were cancer free. According to the authors, these are the highest survival rates reported for patients with T-ALL and T-LL.
“T-cell ALL is a disease that requires the use of a very intense and complex chemotherapy regimen. Historically, about 80% of people live at least 4 years after being treated for their disease, but we felt we could and must do better,” lead study author Kimberly Dunsmore, MD, Virginia Tech Carilion School of Medicine in Roanoke, said in a statement. “Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”
There were 4 arms in the trial. While all patients received the same chemotherapy regimen, known as COG augmented Berlin-Frankfurt-Munster, they were also randomized to receive either high-dose methotrexate in hospital or an escalating dose of methotrexate in an outpatient setting. In addition, patients with moderate or high risk of cancer recurrence were randomized to receive or not receive nelarabine in addition to chemotherapy and cranial radiation.
The researchers found that patients with T-ALL who had an increased risk of recurrence and received nelarabine had a higher 4-year disease-free survival (DFS) rate (88.9%) compared with patients with T-ALL who did not receive nelarabine (83.3%). The group also had higher 4-year DFS compared with patients with T-LL who had an increased risk of recurrence (85%). In general, patients with T-LL did not benefit from the addition of nelarabine, the study found.
Patients with T-ALL who received escalating doses of methotrexate had an 89.8% 4-year DFS compared with 78% for patients who received high-dose methotrexate. Patients with T-ALL who received both nelarabine and escalating doses of methotrexate had the best results with 92.2% disease free at 4 years.
“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,” ASCO President Bruce E. Johnson, MD, FASCO. “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.”
The researchers also found that overall toxicity and neurotoxicity were not significantly different between all 4 arms and were considered acceptable. Future studies, ASCO noted, should examine the use of nelarabine without cranial radiation as doctors move to decrease the use of cranial radiation in order to prevent late side effects, including changes in cognitive abilities, learning disabilities, neuroendocrine changes, and development of secondary malignancy.
Dunsmore KP, Winter S, Devidas M, et al. COG AALL0434: a randomized trial testing nelarabine in newly diagnosed t-cell malignancy. Presented at: American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract 10500. http://abstracts.asco.org/214/AbstView_214_218959.html.