CNS prophylaxis is (mostly) futile in DLBCL.

Area of Science:

• Oncology
• Hematology
• Clinical Medicine

Background:

• Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) significantly worsens patient prognosis.
• CNS relapse risk is approximately 5% overall but higher in specific high-risk patient groups.
• CNS prophylaxis, including high-dose methotrexate (HD-MTX) and intrathecal (IT) chemotherapy, is often used for high-risk DLBCL patients.

Purpose of the Study:

• To review existing literature on the efficacy of CNS prophylaxis with HD-MTX or IT chemotherapy in DLBCL.
• To exclude specific lymphoma subtypes (Burkitt, lymphoblastic leukemia/lymphoma, double/triple hit lymphoma) from the analysis.
• To provide guidance on the use of CNS prophylaxis in DLBCL based on current evidence.

Main Methods:

• Systematic literature review of studies evaluating CNS prophylaxis in DLBCL.
• Analysis focused on high-dose methotrexate (HD-MTX) and intrathecal (IT) chemotherapy regimens.
• Exclusion of specific lymphoma subtypes with established CNS prophylaxis protocols.

Main Results:

• Recent retrospective analyses question the overall efficacy of current CNS prophylaxis strategies.
• Intrathecal (IT) chemotherapy may offer better tolerability compared to high-dose methotrexate (HD-MTX).
• If HD-MTX is administered, it should follow completion of systemic therapy to prevent treatment delays.

Conclusions:

• Current evidence suggests that CNS prophylaxis, whether via HD-MTX or IT chemotherapy, may not provide a clear survival benefit for DLBCL patients.
• Intrathecal chemotherapy is recommended over HD-MTX for better tolerability if prophylaxis is pursued.
• An algorithm is proposed to aid clinical decision-making regarding CNS prophylaxis in DLBCL.