New Treatment Regimens Boost Survival Rates in Children with T-ALL or T-LL

The American Cancer Society estimates that about 5,960 individuals will develop acute lymphocytic leukemia (ALL) in the United States in 2018. T-cell ALL (T-ALL) is a specific type of leukemia that is rare and particularly aggressive, progressing quickly when left untreated.

At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, Illinois, researchers from the Children’s Oncology Group report that 90% of children and young adults with T-ALL or T-cell lymphoblastic lymphoma (T-LL) were alive 4 years after starting treatment in a phase 3 clinical trial. Not only were they alive, but 84% were cancer-free at that time.

Furthermore, the researchers found that patients with moderate to high risk of experiencing T-ALL recurrence stand to benefit by adding nelarabine (Arranon) to standard chemotherapy; in fact, 89% of those who received nelarabine were found to be free of leukemia at four years post-treatment compared with the 83% of those who did not.

“T-cell ALL is a disease that requires the use of a very intense and complex chemotherapy regimen. Historically, 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, professor, Virginia Tech Carilion School of Medicine, said in a recent statement. “Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”

These survival rates are the highest ever reported for these T-cell malignancies.

A total of 1,895 patients with T-ALL (94%) or T-LL (6%) had been enrolled in the trial, which authors are referring to as the largest randomized clinical trial ever performed in these diseases; participants ranged in age from 1 to 30 years.

For the trial, which began in 2007, all patients received COG augmented Berlin-Frankfurt-Munster (aBFM) chemotherapy. In addition to receiving a standard chemotherapy regimen, patients were randomly assigned into one of 2 groups: those who would be given high-dose methotrexate in a hospital, or those who would be given escalating dose methotrexate in an outpatient setting.

Those thought to be at moderate to high risk for cancer recurrence were also randomly assigned into 2 groups: those who would receive nelarabine in addition to standard chemotherapy and cranial radiation, and those who would not.

Overall, the researchers found that a whopping 90.2% of patients who were treated in the trial went on to live at least 4 years; 84.3% did not have cancer at this time. Furthermore, 88.9% of those at increased risk of cancer recurrence who received nelarabine were leukemia-free at 4 years compared with those who did not receive it (83.3%). Patients with T-LL were not found to benefit from nelarabine, however, over 85% went on to live 4 years without disease.

Furthermore, investigators report that T-ALL patients who received escalating doses of methotrexate fared better than those who had received high-dose methotrexate; of these patients randomly assigned to get nelarabine and escalating doses of methotrexate, at 4 years, 92.2% were leukemia-free.

After the first phase of chemotherapy, those who did not experience remission were assigned to be given high-dose methotrexate and nelarabine, and a little over half of these individuals (54.8%) did not exhibit any signs of disease in 4 years’ time.

“This is a significant improvement, as historically only about 20% of people with T-ALL who did not experience cancer remission lived another 3 years,” study authors write.

As for next steps? Health providers are striving to reduce the use of cranial radiation to treat T-cell leukemia due to harmful late-stage side effects. As such, further research is being done to assess potential benefits of using nelarabine in chemotherapy protocols sans cranial radiation.

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