Background: Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) results in dismal prognosis. There is controversy over the treatment method and efficacy of CNS prophylaxis in high risk DLBCL. Although methotrexate (MTX) is the most widely used therapy for CNS prophylaxis, results from previous studies investigating the optimal regimen for CNS prophylaxis remains unclear. Therefore, additional strategies for preventing CNS relapse in DLBCL patients are required. We evaluated the efficacy and safety of different prophylactic regimens (thiotepa plus high-dose methotrexate, high-dose methotrexate alone or intrathecal methotrexate and cytarabine) in newly diagnosed DLBCL patients with high-risk for CNS relapse.

Methods: We retrospectively analyzed records of all newly diagnosed DLBCL patients at high risk for CNS relapse treated at Hunan Cancer Hospital between November 2009 and January 2024. Patients received either thiotepa plus high-dose methotrexate (thiotepa 40mg/ m2, methotrexate 3.5g/m2, T-HD-MTX), high-dose methotrexate alone (methotrexate 3.5g/m2, HD-MTX), or intrathecal methotrexate and cytarabine (IT). The primary endpoint was the rate of CNS relapse, and the secondary endpoints included progression-free survival (PFS) and adverse events (AEs).

Results: 232 newly diagnosed DLBCL patients (128 males; median age 59 years, range, 19-76) with high-risk for CNS relapse was included in this study, of whom 170 patients were Ⅲ-Ⅳ stage, 136 patients were non-GCB and 46 patients were CD5 positive. Prophylactic regimens were as follows: IT MTX in 84 patients (36.2%), HD-MTX in 105 patients (45.3%), and T-HD-MTX in 43 patients (18.5%). With a median follow-up of 43 months, CNS relapse rate was 22.6% (19/84) in IT group, 8.6% (9/105) in HD-MTX group, 2.3% (1/43) in T-HD-MTX group (P＜0.001). The most common AEs were leukopenia (56.5%), thrombocytopenia (32.8%), and anemia (37.5%). Grade 3-4 AEs included leukopenia (10.8%), thrombocytopenia (2.2%), and pneumonia (3.4%), and no severe AEs reported.

Conclusion: Thiotepa plus high-dose methotrexate is an effective and well-tolerated CNS prophylactic regimen for high-risk newly diagnosed DLBCL patients.

Disclosures

No relevant conflicts of interest to declare.

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2024
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