Nelarabine With Chemotherapy Boosted Outcomes in Pediatric and YA Patients With T-Cell Cancers

Surabhi Dangi-Garimella, PhD

A phase 3 study, conducted by the Children’s Oncology Group (COG) in 2007, among children and young adults between ages 1 and 30 diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic leukemia (T-LL) has found a 90% survival rate at 4 years posttreatment initiation—84% of these patients were declared cancer free at that point in their treatment trajectory. Results from this study will be presented at the 2018 American Society of Clinical Oncology Annual Meeting, June 1-5, in Chicago, Illinois.

The COG AALL0434 study enrolled 1895 patients during an 8-year period (January 2007- July 2014) to test nelarabine, an antineoplastic agent directed against T cells, in combination with chemotherapy. The trial had 4 arms; all patients received COG augmented Berlin-Frankfurt-Munster or aBFM chemotherapy. Additionally, they were randomized to receive escalating dose methotrexate without leucovorin rescue + pegaspargase (CMTX) or high-dose methotrexate (HDMTX) + leucovorin rescue. Patients with moderate and high risk were randomized to receive, or not receive, six 5-day courses of nelarabine 650 mg/m2/day, complemented with chemotherapy and cranial radiation.

“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 four years after being treated for their disease, but we felt we could and must do better,” lead author Kimberly Dunsmore, MD, professor, Virginia Tech Carilion School of Medicine in Roanoke, said in a press release. “Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”

For all patients, the overall disease-free survival (DFS) rate was 84.3 +/- 1.1% at 4 years, and overall survival (OS) rate was 90.2 +/- 0.9%. The 4-year DFS rate for T-ALL patients randomized to nelarabine (n = 323) versus no nelarabine (n = 336) was 88.9 +/- 2.2% vs 83.3 +/- 2.5%, (P = .0332).

Among T-ALL patients randomized to CMTX, the 4-year DFS for nelarabine (n = 147) versus no nelarabine (n = 151) was 92.2 +/- 2.8% vs 89.8 +/- 3.0% (P = .3825). For patients randomized to HDMTX, the 4-year DFS was 86.2 +/- 3.2% with nelarabine (n = 176) vs 78.0 +/- 3.7% without nelarabine (n = 185; P = 0.024).

Importantly, there was no advantage of nelarabine treatment for high risk T-LL patients; 4-year DFS was 85.0 +/- 5.6% for nelarabine (n = 60) and it was 89.0 +/- 4.7% for patients who did not receive nelarabine (n = 58; P = .2788).

Overall toxicity and neurotoxicity were acceptable and not significantly different between all 4 arms, the authors concluded.

Future studies are directed to evaluate using nelarabine along with chemotherapy without cranial radiation, to avoid the late side effects associated with radiating the brain, including cognitive changes, learning disabilities, neuroendocrine changes and the development of secondary cancers.

Dunsmore KP, Winter S, Devidas M, et al. COG AALL0434: A randomized trial testing nelarabine in newly diagnosed t-cell malignancy. J Clin Oncol. 2018;36,(suppl; abstr 10500).
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