CNS Prophylaxis Shows Limited Effectiveness in Preventing CNS Relapse in DLBCL

Intrathecal methotrexate did not prevent central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) but was associated with financial toxicity and a high rate of side effects, according to results from a retrospective, single-institution study published in Clinical Lymphoma Myeloma and Leukemia.

“CNS relapse is an infrequent but serious and challenging complication in DLBCL that carries a dismal prognosis,” wrote corresponding author Mojtaba Akhtari, MD, of Loma Linda University, Loma Linda, California, and study coauthors. “While several risk factors have been identified to stratify the risk for CNS relapse including the 2015 CNS Internal Prognostic Index (CNS-IPI), controversy still remains regarding the indication, timing, and method of CNS prophylaxis.”

The retrospective study investigated whether intrathecal methotrexate reduced CNS relapse in 194 patients with DLBCL who received treatment at Loma Linda University Cancer Center between January 2010 and August 2022. Researchers also looked at the side effect profile and cost. 

In patients with CNS-IPI-determined intermediate to high CNS relapse risk, intrathecal methotrexate did not reduce the 1-year risk for CNS relapse, according to the study. However, the median time to CNS relapse was longer in patients who received intrathecal methotrexate: 13.5 months, compared with 7 months in patients who did not receive prophylaxis.

Adverse side effects of any kind resulting from intrathecal methotrexate were reported by 52.8% of patients. Grade 2 and 3 adverse events affected nearly a quarter of patients, the study found.

The cost of CNS prophylaxis over a patient’s treatment course was as high as $20,140. Estimates put the average cost at about $8059.

“These findings suggest that intrathecal methotrexate has limited and potential transient effectiveness in preventing CNS relapse,” researchers wrote. “Given the high rate of side effects and significant cost of intrathecal methotrexate, we recommend that clinicians carefully consider the risks and benefits of prophylaxis before prescribing intrathecal methotrexate for CNS prophylaxis.”

Reference:
Hino C, Lacy C, Brothers J, et al. Factors influencing physician discretion to administer CNS prophylaxis in diffuse large B cell lymphoma: a single institution retrospective study. Clinical Lymphoma Myeloma and Leukemia. Published online July 6, 2023. https://doi.org/10.1016/j.clml.2023.06.009