Key Points
• In the current study, researchers compared the efficacy of different prophylactic regimens in 585 newly diagnosed DLBCL patients at high-risk for CNS relapse. These participants were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens, with 295 (50%) receiving prophylaxis.
• They found that data supporting the benefit of methotrexate for CNS prophylaxis is transient, and that better prophylaxis regimens are needed. Moreover, no benefit for high-dose methotrexate was observed.
• “Although in our series the risk of CNS relapse was similar regardless the use of prophylaxis, we found that within the first year from diagnosis the risk was higher in patients who did not receive prophylaxis compared to patients who received IT or HD-MTX with a risk of 7.1% vs. 2% vs. 2.4%, respectively. However, over time, the risk became similar between groups, raising up to 5.6% and 5.2% at 5 years in the HD-MTX and IT groups, respectively. These findings were not observed in previous studies analyzing the role of CNS prophylaxis. However, the median follow-up in these studies was around 2.5 years, so late relapses might have been underestimated,” the authors wrote.
• “Our evidence suggests CNS prophylaxis might help to partially control undetected CNS disease present at diagnosis delaying the occurrence of CNS relapse, rather than preventing it. Furthermore, the use of CNS prophylaxis might not prevent from late CNS relapse in the HR-CNS [high-risk CNS] population,” they added.
• In accordance with other recent data, the investigators observed that the presence of non-GCB phenotype determined by immunohistochemistry heightened the risk of CNS relapse in the high-risk CNS population.

Key Points
• Methotrexate (MTX) is the most popular means of CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), however the best regimen for its administration remain to be elucidated. In the current trial, researchers assessed the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL at high risk of CNS relapse. These patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens, with 50% receiving CNS prophylaxis. Of note, 14% were given intrathecal (IT) MTX and 86% were given high-dose MTX (14%)
• CNS relapse at 1 year was 2% in patients who received prophylaxis versus 7.1% in those who did not. Nevertheless, this difference in risk became less marked over time, or 5.6% vs. 7.5%, at 5 years, respectively. According to the authors, prophylaxis “tended to delay CNS relapse rather than prevent it.”
• CNS relapse risk at 5 years was similar in both IT MTX and HD-MTC groups, or 5.6% vs. 5.2%, respectively. The authors suggested that in addition to demonstrating no advantage in the use of HD-MTX compared with IT MTX, more generally, the benefit of MTX for CNS prophylaxis is transient, which means that more effective prophylactic regimens are necessary.
• “In recent years, the use of HD-MTX administrated mid chemotherapy cycles or after completing systemic chemotherapy was proposed as an alternative strategy to prevent CNS recurrence. The rational is based on the observation that CNS relapses frequently involve the brain parenchyma,” the authors wrote.
• “Our evidence suggests CNS prophylaxis might help to partially control undetected CNS disease present at diagnosis delaying the occurrence of CNS relapse, rather than preventing it. Furthermore, the use of CNS prophylaxis might not prevent from late CNS relapse in the HR-CNS population,” they added.
• In accordance with other recently published data, the authors found that the presence of non-GCB phenotype determined by immunohistochemistry heightens the risk of CNS relapse in those at high risk for CNS relapse.