Efficacy of intravenous high-dose methotrexate in preventing relapse to the central nervous system in R-CHOP(-like)-treated, high-risk, diffuse large B-cell lymphoma patients and its effect on mortality: a systematic review and meta-analysis.

Abstract

To evaluate: 1) whether addition of prophylactic intravenous HD-MTX reduces the risk of CNS relapse in high-risk DLBCL patients treated with R-CHOP or similar and 2) whether HD-MTX prophylaxis confers an overall survival benefit, irrespective of CNS relapse. A systematic search of MEDLINE/PubMed and EMBASE on DLBCL patients at high risk of CNS relapse treated with R-CHOP or similar receiving HD-MTX as intervention and a comparator arm receiving no prophylaxis and/or IT prophylaxis. Risk of Bias was estimated using the ROBINS-I tool and the quality of the evidence by the GRADE approach. Finally, a meta-analysis based on the systematic review was conducted. A total of 1812 studies were screened. No RCT's were identified. Seven observational studies comprising 1661 patients met inclusion criteria. We found a statistically non-significant relative risk of 0.54 [0.27-1.07, 95% CI] of CNS relapse for patients receiving HD-MTX vs. controls. The meta-analysis investigating mortality demonstrated a relative risk of death of 0.70 [0.44-1.11, 95% CI] for HD-MTX treated vs. controls. The overall risk of bias was adjudged as "serious" and the quality of the evidence was rated as low. Our data indicate that HD-MTX does not prevent, or at best, only slightly reduces the risk of CNS relapse and confers no survival benefit.