Hispanic pediatric patients undergoing treatment for acute lymphoblastic leukemia (ALL) had a risk of methotrexate toxicity that was more than twice that of non-Hispanic whites, according to results of a prospective multicenter study.
Dr. Michael E. Scheurer
Methotrexate toxicity often led to treatment modification or delays, which may have increased relapse risk in the Hispanic patients, according to investigator Michael E. Scheurer, PhD, MPH, of Baylor College of Medicine, Houston, and his colleagues.
“We had observed that our Hispanic patients tended to experience neurotoxicity more often than other groups, but we were surprised to see the magnitude of the difference,” Dr. Scheurer said in statement.
The study, described in Clinical Cancer Research, involved 280 patients with newly diagnosed ALL enrolled at one of three major U.S. pediatric cancer treatment centers. Nearly half of the patients (48.2%) were Hispanic, and approximately 86% had a diagnosis of pre B-cell leukemia.
The patients, who had a mean age of 8.4 years at diagnosis, were treated with modern ALL protocols and were followed from diagnosis to the start of maintenance/continuation therapy.
Methotrexate toxicity was seen in 39 patients at the time of the analysis. Of those patients, 29 (74.4%) were Hispanic, Dr. Scheurer and his coauthors reported.
Compared with non-Hispanic whites, Hispanics had a high risk of methotrexate neurotoxicity, even after the researchers accounted for age, sex, ALL risk stratification, and other factors (adjusted hazard ratio, 2.43; 95% confidence interval, 1.06-5.58).
Among nine patients who experienced a second neurotoxic event, all were Hispanic.
Patients who had neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate, and slightly lower intravenous methotrexate doses. About three-quarters of the patients experiencing methotrexate toxicity received leucovorin after intrathecal methotrexate, according to the investigators, who noted that leucovorin may interact with methotrexate and reduce efficacy.
“These findings may help us better understand what factors contribute to poorer survival among Hispanic patients with ALL,” wrote Dr. Scheurer and his coauthors.
Relapse occurred in 15.4% of patients with neurotoxicity (6 of 39 patients), and in 2.1% of patients with no neurotoxicity (13 of 241 patients).
Taken together, the findings add to the growing body of evidence that Hispanics and other minority pediatric patients with ALL experience “significant disparities” in treatment outcomes, according to the investigators.
That body of evidence includes several recent cases series that suggest Hispanic patients with ALL have a high prevalence of methotrexate neurotoxicity.
It remains unclear why Hispanic patients would have a higher risk of methotrexate toxicity, and that must be explored in future studies, the investigators said.
The research team is currently investigating biomarkers that may help identify patients at risk of methotrexate toxicity up front. “If we can identify these at-risk patients, we can potentially employ strategies to either fully prevent or mitigate these toxicities,” Dr. Scheurer said in a statement.
The research was supported by the National Institutes of Health and Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, a St. Baldrick’s Foundation Consortium Research Grant. The researchers reported having no potential conflicts of interest.
SOURCE: Taylor OA et al. Clin Cancer Res. 2018 Sep 11. doi: 10.1158/1078-0432.CCR-18-0939.