Patients with diffuse large B-cell lymphoma (DLBCL) can experience central nervous system (CNS) relapses, a rare but potentially fatal event. Authors of a research letter to Blood Advances evaluate the results of a post hoc analysis that found that lenalidomide after chemotherapy did not reduce the risk of CNS relapse.

Methotrexate is currently used as prophylactic treatment for CNS relapse, but high-dose intravenous methotrexate has significant toxicity, making it intolerable for some patients.

Lenalidomide is an immunomodulating agent that penetrates the blood-brain barrier that has had mixed results when used as maintenance therapy in DLBCL after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone).

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The multicenter, double-blinded, randomized, phase 3 REMARC trial ( Identifier: NCT01122472) included 650 previously untreated patients with DLBCL. Patients who had a partial response (PR) or complete response (CR) after first line R-CHOP were randomized to receive maintenance lenalidomide or placebo for 2 years.

A total of 164 patients received intrathecal methotrexate and lenalidomide; 4 patients received high-dose IV methotrexate and lenalidomide. After median of 81.1 months of follow-up, 34% (221) of patients relapsed, with 22 of those relapses being CNS-specific relapses.

Out of 22 patients, 6 with CNS-specific relapses were on lenalidomide maintenance therapy, while 2 were on placebo. Patients on lenalidomide had a median time to CNS relapse of 12.2 months, compared with 32 months for placebo.

Overall, patients who received any prophylaxis had an estimated 2-year CNS relapse rate of 2.5%, compared with 1.6% for patients who did not receive prophylaxis, but the difference was not significant (P =.9331).

 CNS relapse often occurs early in the disease course, and the CNS relapse rate of 3% in the REMARC trial is consistent with the expected rate in patients with DLBCL.

The authors conclude that in this trial, lenalidomide did not reduce the incidence of CNS relapse in older (age 60-80 years) patients with DLBCL.

Disclosure: The study authors have declared affiliations with pharmaceutical, biotech, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Bernard S, Ghesquieres H, Casasnovas RO, et al. Incidence of central nervous system relapses in patients with DLBCL treated with lenalidomide as maintenance after R-CHOP. Blood Adv. 2021;5(15):2965-2968. doi:10.1182/bloodadvances.2021004766