ASCO 2018-BEST RESULTS FOR T-CELL LEUKEMIA

The largest trial that has been completed to date in children and young adults with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) has yielded the "best survival data ever" in this patient population, researchers said at a press briefing.

The results from the Childrens Oncology Group AALL0434 trial will be presented at the forthcoming American Society of Clinical Oncology (ASCO) 2018 annual meeting (abstract 10500). The society chose to highlight this study among others at a premeeting presscast.

ASCO President Bruce E. Johnson, MD, commented that it was "quite an achievement" to put together such a large study for this patient population.

"Before they embarked on this, about only 80% of the patients were surviving up until 4 to 5 years, and this improved by about 10%," said Johnson, who is also chief clinical research officer and institute physician at the Dana-Farber Cancer Institute in Boston, Massachusetts.

In the trial, nelarabine (Arranon, GlaxoSmithKline) was added to standard chemotherapy. Nelarabine is already approved for relapsed or recurrent disease, but "in this particular setting, moving it up front, closer to the initial treatment, improved the outcomes for those patients," he said.

Largest Trial to Date

The trial is the largest clinical trial for children and young adults with T-ALL and T-cell lymphoblastic lymphoma (T-LL), commented lead author Kimberly Dunsmore, MD, of the Virginia Tech Carilion School of Medicine in Roanoke, and it has shown the "best survival data ever" in this patient population.

Across all randomized groups, the 4-year overall survival rate was 90.2%, and disease-free survival (DSF) rate was 84.3%.

"Patients who didn't achieve induction remission had a 54% survival at 4 years, more than double past survival rates," Dunsmore said. "And even though T-LL patients didn't receive a benefit from nelarabine, they still had very good survival of 85% at 4 years."

Improved Outcomes Frontline

The study enrolled 1895 patients aged 1 to 30 years who had either T-ALL (94%) or T-LL (6%). The patients were randomly assigned to one of four regimens: escalating doses of methotrexate (CMTX) alone, CMTX with six courses of nelarabine (5-day courses at 650 mg/m²/day), high-dose methotrexate (HDMTX) alone, and HDMTX with six courses of nelarabine.

Across all groups, the 4-year overall survival rate was 90.2%.

In Children's Oncology Group T-ALL trials conducted from 2000 to 2005, for such patients, the overall survival rate at 4 years was around 80%.

The 4-year DFS rate for T-ALL patients who received nelarabine was 88.9%; for patients who did not receive nelarabine, the 4-year DFS was 83.3% (P = .0332).

For the patients who received CMTX, 4-year DFS also favored the nelarabine group (92.2% vs 89.8%; P = .3825).

In the HDMTX groups, the 4-year DFS was 86.2% vs 78.0%, also favoring nelarabine.

The authors note that in a four-arm comparison, differences in DFS were highly significant (P = .002), and there were no significant interactions between MTX and nelarabine (P = .41).

For patients with T-ALL in whom induction therapy failed and who were assigned to HDMTX plus nelabarine, the 4-year DFS was 54.8%. Adding nelarabine to the regimen failed to show a survival advantage for patients with high-risk T-LL (85% vs 89%; P = .2788).

Dunsmore noted that the next steps will be to examine the use of nelarabine in protocols that do not include cranial irradiation, with a view toward decreasing long-term neurologic side effects.

The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and support from the St. Baldrick's Foundation. Dr Dunsmore has relationships with TypeZero, Novo Nordisk, and Tandem Diabetes Care; several coauthors also have multiple relationships with industry.

American Society of Clinical Oncology (ASCO) 2018. Abstract 10500, to be presented June 2, 2018.