A combination of Arranon (nelarabine) and standard chemotherapy led to the highest survival rates seen to date in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), a Phase 3 clinical trial shows.
Four years after starting their treatment, 90 percent of these patients were still alive, and 84 percent were cancer-free. However, the treatment did not improve the outcomes in T-cell lymphoblastic lymphoma (T-LL) patients.
These findings show that despite the high survival rates of this population, there’s still room for improvement in their long-term outcomes without raising safety concerns.
The data will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting, taking place June 1-5 in Chicago. The presentation is titled “COG AALL0434: A randomized trial testing nelarabine in newly diagnosed t-cell malignancy.”
Arranon, by Novartis, is marketed as Atriance in the European Union. It is approved for the treatment of T-ALL and T-LL patients who did not respond to at least two prior lines of therapy. Now researchers are examining Arranon’s effectiveness in patients who have not received any prior treatment.
The trial (NCT00408005) enrolled 1,895 patients, between 1 and 30 years old, with newly diagnosed T-cell cancers. Most (94%) had T-ALL, and the remaining had T-LL. This was the largest randomized clinical trial ever performed in newly diagnosed T-ALL and T-LL.
“T-ALL is a disease that requires the use of a very intense and complex chemotherapy regimen. Historically, about 80% of people live at least four years after being treated for their disease, but we felt we could and must do better,” Kimberly Dunsmore, MD, a professor at the Virginia Tech Carilion School of Medicine in Roanoke and lead study author, said in a press release. “Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”
Participants were treated with the standard chemotherapy regimen — called COG augmented Berlin-Frankfurt-Munster chemotherapy — with either high-dose methotrexate or gradually increasing doses of methotrexate.
Patients with a moderate or high risk for cancer recurrence were then randomly assigned to receive Arranon or not.
Of the T-ALL patients, 90.2% were still alive after four years, and 84.3% were cancer-free.
For those who received Arranon, 88.9% remained disease-free at least four years after starting treatment, compared with only 83.3 percent of the moderate- to high-risk patients who did not receive Arranon.
However, Arranon did not improve the outcomes of T-LL patients, 85% of whom were disease-free at four years, compared with 89% of the control patients.
Arranon was particularly beneficial for T-ALL patients who received escalating doses of methotrexate, 92.2% of whom were leukemia-free at four years, compared with 86.2% in the high-dose methotrexate group.
A total of 43 patients did not achieve cancer remission after the initial treatment phase and were given high-dose methotrexate plus Arranon. More than half (54.8%) of them survived four years without signs of the disease. This is a significant improvement, because historically only about 20 percent of T-ALL patients who do not achieve cancer remission live another three years.
The addition of Arranon did not raise any new safety concerns, compared with standard chemotherapy. All treatment regimens showed acceptable overall toxicity and neurotoxicity profiles.
The researchers believe that Arranon “should become a new standard of care” for children and young adults with T-ALL.
“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. 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,” said Bruce E. Johnson, MD, ASCO president.