Escalated vs High-Dose Methotrexate in T-Cell ALL

Patients with T-cell acute lymphoblastic leukemia (T-ALL) treated with an escalating methotrexate (MTX) regimen had survival outcomes superior to those of patients who received chemotherapy plus high-dose MTX, according to the results of a recent clinical trial (J Clin Oncol. 2018 Aug 23. Epub ahead of print).

Findings from the Children’s Oncology Group (COG) AALL0434 trial also demonstrated lower rates of relapse—including relapse with central nervous system (CNS) involvement—in patients who received the escalating MTX (ie, Capizzi-style MTX) versus high-dose MTX regimen.

The Children’s Oncology Group AALL0434 Clinical Trial

Citing a lack of clarity around the best timing and order in which to administer key therapies for patients with T-cell ALL (eg, asparaginase, MTX), lead investigator Stuart S. Winter, MD, Children’s Minnesota Cancer and Blood Disorders Program, Minneapolis, and colleagues compared the 2 MTX administration approaches in patients with T-cell ALL receiving an augmented Berlin-Frankfurt-Muenster (ABFM) chemotherapy regimen.

“Although MTX has long been recognized for its importance in the treatment of ALL, questions about its dose and integration into multiagent therapy have merited continued investigation, they said.

Out of a total of 1895 patients accrued for the trial from 2007 to 2014, 1031 patients with T-cell ALL and no CNS3 disease or testicular leukemia were randomized to a treatment regimen of ABFM chemotherapy plus C-MTX (n = 519) or high-dose MTX (n = 512). Aside from those with low-risk features, all patients also received prophylactic or therapeutic cranial irradiation.

Escalated Regimen Superior to High-Dose Approach

The 5-year disease-free and overall survival rates for the 1031 patients randomized to the MTX regimens were 88.4% (95% confidence interval [CI], 85.7%-91.1%) and 91.6% (95% CI, 89.2%-94.0%), respectively.

In April 2015, when interim monitoring occurred, a predetermined efficacy monitoring boundary was crossed, with estimated 4-year disease-free survival rates of 92.5% (95% CI, 89.0%-96.0%) and 86.1% (95% CI, 81.4%-90.8%) for patients who received escalated MTX and high-dose MTX, respectively (P = .017).

Patients in the escalated MTX arm had 32 relapses, including 6 with CNS involvement, whereas those in the high-dose TMX arm had 59 relapses, including 23 with CNS involvement.

Dr Winter and colleagues concluded that the results of the COG AALL0434 trial established the superiority of ABFM chemotherapy plus escalated MTX to ABFM plus high-dose MTX in patients with T-cell ALL.—Janelle Bradley