Adding high-dose cytarabine to high-dose methotrexate (MTX) may improve outcomes in patients with primary CNS lymphomas, according to a small controlled trial, albeit at the price of increased toxicity.

Primary CNS lymphoma is uncommon, and there are few controlled trials of therapy. Current first-line therapy is high-dose MTX, however evidence suggests that high-dose cytarabine may be beneficial. This open-label study compared high-dose cytarabine plus MTX with high-dose MTX alone. Participants were adult patients aged up to 75 with newly-diagnosed non-Hodgkin lymphoma exclusively localised to the CNS, eyes, or cranial nerves. They were randomised to treatment with four courses of MTX on day 1, or four courses of MTX on day 1 combined with cytarabine, twice a day (every 12 h), on days 2 and 3; both groups repeated treatment every 3 weeks. Primary endpoint was complete remission rate after primary chemotherapy.

There were 86 patients assessed for inclusion, of whom 79 were enrolled and randomised (6 didn’t meet inclusion criteria, 1 did not wish to participate); 40 received MTX alone, 39 the combination. Overall, there were more complete responses to combination treatment compared to MTX alone: 18 vs. 7 (46% vs. 18%; p=0.006). There were also more partial responses in the combination group for overall response rates of 69% vs. 40% (p=0.009). Haematological toxicity was more frequent in the combination group, with grade 3 to 4 haematological toxicity in 92% vs. 15%; there were also more deaths due to toxicity in the combination group (3 vs. 1).

The authors conclude that in patients aged up to 75 with primary CNS lymphoma, adding cytarabine to MTX improves outcome with acceptable toxicity. They comment, nevertheless, that outcomes in this condition are unsatisfactory and work is needed to identify other drugs with activity.

An accompanying Comment discusses the study: the authors commend the trial team for their work, and suggest further areas for research in this condition.