Real-World Data Suggest Systemic High-Dose and Intrathecal MTX Lower CNS Relapse Incidence for DLBCL

The 3-year follow-up analysis of 4 treatment groups who received CNS prophylaxis found a decreased incidence of CNS relapse for patients with high-risk diffuse large B-cell lymphoma, although the data were not statistically significant.

The addition of systemic high-dose methotrexate (MTX) to intrathecal (IT) MTX treatment led to a lower incidence of central nervous system (CNS) relapse for patients with high-risk diffuse large B-cell lymphoma (DLBCL), although these data were not statistically significant, according to research published in JCO Global Oncology.

“Our study on the [real world data] add to the growing body of nonrandomized data favoring the combination strategy of systemic high-dose MTX and IT MTX for the prophylaxis of CNS relapse in DLBCL,” wrote the investigators.

A total of 110 of the 145 identified patients with DLBCL who received CNS prophylaxis were included in the study’s final analysis. These patients received standard systemic therapy and were divided into 4 separate groups based on CNS prophylaxis strategy and risk categories via the CNS International Prognostic Index (IPI).

Group 1 included 46 patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy with or without rituximab (Rituxan) plus IT MTX alone. Group 2 had 12 patients receiving CHOP therapy with or without rituximab plus high-dose MTX alone. Group 3 included 41 patients who received CHOP therapy with or without rituximab plus IT and high-dose MTX. Eleven patients in group 4 received Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) chemotherapy plus IT MTX and/or high-dose MTX.

The CNS relapse rate at a 3-year follow-up was 8.6% in group 1, 8.3% in group 2, 4.8% in group 3, and 18% in group 4 (P = .64). Using CNS IPI risk categories to evaluate high-, intermediate-, and low-risk groups, the CNS relapse rates were 16.6%, 10.1%, and 0%, respectively.

More, the 3-year overall survival rate was recorded at 69% for group 1, 75% for group 2, 80% for group 3, and 45% for group 4 (P = .71).

“In this study, we have presented real-world data on 110 patients with DLBCL who received three different strategies of CNS prophylactic therapy and compared their outcomes within the limitations of a retrospective review,” wrote the investigators.

The research team acknowledges the potential for bias in this retrospective analysis but explained that the implementation of the CNS IPI to categorize risk helped to mitigate “heterogeneity in the baseline risk assessment.”

The investigators recognize that a prospective study focusing on CNS prophylactic strategy could provide valuable data, but the implementation of such research is difficult due to the rarity of CNS relapses in DLBCL.

“Our study adds to the earlier observations made in a similar retrospective study indicating a lower incidence of CNS relapse with the addition of systemic high-dose MTX to IT MTX alone,” wrote the investigators.


Faqah A, Asif S, Goksu SY, Sheikh HS. Real-World Data (RWD) on the 3-Year Follow-Up Outcomes of Different CNS Prophylaxis Strategies Across CNS-IPI Risk Groups in Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma. JCO Global Oncol. 2021;7:486-494. doi:10.1200/GO.20.00422