In an analysis reported in the Journal of Clinical Oncology, Wilson et al found that prophylactic high-dose methotrexate does not provide significant benefit in reducing central nervous system (CNS) relapse in patients with ultra–high-risk large B-cell lymphoma (LBCL).
Study Details
The analysis used data from two prior retrospective analyses to identify a cohort of patients with ultra–high-risk large B-cell lymphoma, defined as those with at least one of the following characteristics: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; and/or three or more extranodal sites. Patients were treated with or without HD-MTX. The primary outcome measure was CNS relapse rate (isolated or with concurrent systemic relapse).
Key Findings
The analysis included 1,923 ultra–high-risk patients; of these, 1,051 had not received HD-MTX and 872 had received HD-MTX prophylaxis.
The 3-year overall CNS relapse rates were 9.3% in the no–HD-MTX group vs 8.1% in the HD-MTX group (adjusted hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 0.82–1.57). The 3-year isolated CNS relapse rates were 5.9% vs 5.7% (adjusted HR = 1.03, 95% CI = 0.69–1.53).
In a landmark analysis of all responding patients with no progression at 6 months, 3-year CNS relapse rates were 6.7% among 782 patients in the no–HD-MTX group vs 6.6% among 773 patients in the HD-MTX group (adjusted HR = 0.95, 95% CI = 0.62–1.44).
The investigators concluded: “To our knowledge, this is the largest international comparative data set of patients with LBCL with [ultra–high-risk] features showing no significant reduction in CNS relapse with HD-MTX in all [ultra–high-risk] or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.”
Matthew R. Wilson, MBChB, MD, of Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Ministry of Health of the Czech Republic and NIHR Leicester Biomedical Research Center. For full disclosures of the study authors, visit ascopubs.org.
