CNS Prophylaxis in Diffuse Large B-Cell Lymphoma & Its Outcomes- an Institutional Review

Background: Diffuse large B-cell lymphoma (DLBCL) has an approximately 5% risk of recurrence in the central nervous system, and carries a very poor prognosis. Prophylactic intrathecal chemotherapy (ITC) with agents such as Methotrexate (MTX) can mitigate the risk of recurrence and improve survival. We report a single-institution, retrospective analysis of the effect of ITC administration on outcomes in patients with DLBCL, based on CNS-IPI risk stratification.

Methods: We screened 325 DLBCL patients from our tumor registry- of these only 292 had clinical information to risk-stratify per IPI scoring- low-risk, n = 54, intermediate-risk, n = 198, and high-risk n = 40. These patients then further categorized based on the NCCN prognostic model to assess the risk of CNS disease (CNS-IPI) which includes age >60, LDH >normal, ECOG >1, Stage III or IV, Extranodal involvement >1 site, kidney or adrenal gland involvement with scores 0-1 low-risk, 2-3 intermediate-risk, and 4-6 or kidney or adrenal involvement as high-risk. The effect of ITC administration on outcomes such as overall survival (OS) at 1-year (yr) and 5-yr were calculated using univariate two-group comparisons.

Results: Demographic and clinical variables include- Age >60- 61% (n=201); mostly Caucasians- 71%(n=199); Germinal Center(GC) 25%(n=73), non-GC 74%(n=212); mean IPI score-2.8(n=196), R-CHOP-87%(n=233); and, ITC in 15%(n=45). Seven patients in low-risk patients received ITC for unclear reasons. Intermediate risk patients treated with ITC showed a trend towards 90% (n=26) 1yr OS, and 67%(n=8) 5-yr survival compared to who did not receive ITC (non-ITC) who had 84%(n=127) 1-yr, and 55%(n=52) 5-yr OS (p-value 0.57 and 0.43 respectively). High-risk patients treated with ITC showed a trend towards 100%(n=3) 1-yr, and 0% 5-yr OS compared to non-ITC who had 85%(n=23) 1-yr , and 29%(n=5) 5-yr OS (p-value 1.0 and 1.0 respectively).

Conclusions: Our results suggest that in DLBCL patients with the intermediate-risk group may benefit from intrathecal chemotherapy. Our study is limited owing to small sample size in each subset of CNS risk stratification- this limits the interpretation of the results, and should be interpreted cautiously given nonsignificant P-values. However, we believe these results can encourage further research to evaluate the effect of CNS prophylaxis in the intermediate-risk group of DLBCL patients.