Immunochemotherapy using rituximab (RTX) and high-dose methotrexate (HD-MTX): an evaluation of the addition of RTX to HD-MTX in recurrent primary central nervous system lymphoma (PCNSL)

There is increasing evidence that MTX-based chemotherapy is superior to HD-MTX alone. Rituximab (RTX) is effective in a variety of B-cell lymphomas and may enter the brain. The purpose of this study is to evaluate the addition of RTX to HD-MTX in recurrent primary central nervous system lymphoma (PCNSL). Patients diagnosed with recurrent PCNSL at our institution between 2004 and 2009 were treated with HD-MTX (3.5-5.5 g/m2) every 2 weeks. From 2010, RTX (375 mg/m2) was administered every 2 weeks along with HD-MTX. Fifteen recurrences in 10 patients were treated with HD-MTX alone (MTX group). Another 15 recurrences in 10 patients were treated with RTX and HD-MTX (RTX group). In 13 (86.6%) of the 15 recurrences in both groups the pre-planned chemotherapy cycles were completed. In the MTX group, 10/15 (66.6%) recurrences achieved a complete response (CR/CRu), 2/15 (13.3%) recurrences achieved a partial response (PR) and 3/15 (20%) recurrences had progressive disease (PD). In the RTX group, the CR/CRu, PR and PD rates were the same as that in the MTX group. The median time to tumor progression (mTTP) was 9.1 months (range, 1.4-120.9 months) in the MTX group and 7.8 months (range, 0.9-52.3 months) in the RTX group. We found no significant difference in mTTP (9.1 vs. 7.8 months, HR 1.02, 95% CI 0.48-2.18, P = 0.94) between the two groups. All treatment-related toxicities were manageable without any severe events. The addition of RTX to HD-MTX may not be a promising strategy for recurrent PCNSL. A future study with a larger sample size, longer follow-up, or different RTX dosing/schedule is warranted.