High-dose methotrexate without CNS benefit in high-risk DLBCL


Patients at high diffuse risk B cell lymphoma (DLBCL) have a risk of more than 10% relapse of the central nervous system (CNS) and the use of high prophylactic doses methotrexate (HD-MTX) has been proposed as a preventive measure.

However, the use of prophylactic HD-MTX did not improve CNS outcomes or the survival of patients with high-risk DLBCL, but was associated with increased toxicity, according to the results of a retrospective study by Hyehyun Jeong, MD, of Ulsan University. 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, vincristina, and prednisone): patients treated with high-risk DLBCL. The evaluation was based on the physician’s initial treatment intention (ITT) on the use of prophylactic HD-MTX.

A total of 5,130 patients were classified in an ITT HD-MTX group and an equal number in a non-ITT HD-MTX group, according to the report, published online at Blood advance.

Equivalent results

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 (Pg = .96). Three-year progression-free survival and overall survival rates in the ITT HD-MTX and non-ITT HD-MTX groups were 62.4% versus 64.5% (Pg = 0.94) and 71.7% against 71.4% (Pg = .7), respectively. In addition, matching propensity score analyzes showed no significant differences in time to CNS relapse, progression-free survival, or overall survival, according to the researchers.

One of the main concerns, however, was the increase in toxicity observed 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 levels of alanine aminotransferase (ALT), a marker for liver damage. In addition, the ITT HD-MTX group tends to have a higher incidence of highs creatinine during treatment compared to the non-ITT HD-MTX group.

The researchers suggested that the HD-MTX group also showed a more common delay in treatment or a dose reduction in R-CHOP, which could be attributed to toxicities related to HD-MTX intercalated treatments between R cycles. -CHOP, which may result in a reduced dose. R-CHOP intensity that could play a role in the lack of a survival benefit observed with additional HD-MTX.

“Another vital issue to consider is that HD-MTX treatment requires hospitalization because hydration and intensity are leucovorin a bailout is needed, which increases medical costs, “the authors added.

“This real-world experience, unique in its scope and analytical methods, should provide comprehensive information on the role of HD-MTX prophylaxis to help guide current practice, given the lack of potential clinical evidence in this population of patients, ”the researchers said. he concluded.

The authors reported that they had no concurrent financial interests.

This article originally appeared on MDedge.com, which is part of the Medscape professional network.

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