High-Dose Methotrexate of No CNS Benefit in High-Risk DLBCL
Patients with high-risk diffuse large B-cell lymphoma (DLBCL) have a greater than 10% risk of central nervous system (CNS) relapse, and the use of prophylactic high-dose methotrexate (HD-MTX) has been proposed as a preventative measure.
However, the use of prophylactic HD-MTX did not improve CNS or survival outcomes of patients with high-risk DLBCL, but instead was associated with increased toxicities, according to the results of a retrospective study by Hyehyun Jeong, MD, of University of Ulsan College of Medicine, Seoul, Republic of Korea, and colleagues.
The researchers evaluated the effects of prophylactic HD-MTX on CNS relapse and survival outcomes in newly diagnosed R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)–treated patients with high-risk DLBCL. The assessment was based on the initial treatment intent (ITT) of the physician on the use of prophylactic HD-MTX.
A total of 5,130 patients were classified into an ITT HD-MTX group and an equal number into a non-ITT HD-MTX group, according to the report, published online in Blood Advances.
The study showed that the CNS relapse rate was not significantly different between the two groups, with 2-year CNS relapse rates of 12.4% and 13.9%, respectively (P = .96). Three-year progression-free survival and overall survival rates in the ITT HD-MTX and non-ITT HD-MTX groups were 62.4% vs. 64.5% (P = .94) and 71.7% vs. 71.4% (P = .7), respectively. In addition, the propensity score–matched analyses showed no significant differences in the time-to-CNS relapse, progression-free survival, or overall survival, according to the researchers.
One key concern, however, was the increase in toxicity seen in the HD-MTX group. In this study, the ITT HD-MTX group had a statistically higher incidence of grade 3/4 oral mucositis and elevated alanine aminotransferase (ALT) levels, a marker for liver damage. In addition, the ITT HD-MTX group tended to have a higher incidence of elevated creatinine levels during treatment compared with the non-ITT HD-MTX group.
The HD-MTX group also showed a more common treatment delay or a dose reduction in R-CHOP, which might be attributable to toxicities related to intercalated HD-MTX treatments between R-CHOP cycles, the researchers suggested, potentially resulting in a reduced dose intensity of R-CHOP that could play a role in the lack of an observed survival benefit with additional HD-MTX.
“Another vital issue to consider is that HD-MTX treatment requires hospitalization because intensive hydration and leucovorin rescue is needed, which increases the medical costs,” the authors added.
“This real-world experience, which is unique in its scope and analytical methods, should provide insightful information on the role of HD-MTX prophylaxis to help guide current practice, given the lack of prospective clinical evidence in this patient population,” the researchers concluded.
The authors reported that they had no competing financial interests.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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