Rituximab-Lenalidomide-Ibrutinib Combination for Relapsed/Refractory Primary CNS Lymphoma: A Case Series of the LOC Network

Abstract

Background and objectives: To evaluate the efficacy and tolerance of the association rituximab-lenalidomide-ibrutinib (R²I) in relapsed/refractory (R/R) primary CNS lymphoma (PCNSL).

Methods: R/R PCNSL patients treated with R²I were retrospectively selected and analyzed from the French LOC database.

Results: Fourteen patients (median age: 63 years, median Karnofsky Performance Status: 75%) received R²I, administered after a median of 2 previous lines of chemotherapy, including autologous stem cell transplantation (ASCT) in 5 cases. The best response was complete response in 4/14 patients and partial response in 4/14 patients, achieved in a median of 2.5 months. Three responder patients received consolidation treatment (WBRT: N = 2, ASCT: N = 1) after R²I, and R²I served as a bridge before CAR-T cell therapy for one patient. R²I was discontinued due to toxicity in 3/14 patients. There were no toxicity-related deaths.

Discussion: The R²I combination resulted in a high rate of response of rapid-onset in heavily pretreated patients with poor prognosis, with manageable toxicity, and allowed 3 patients to proceed to consolidation. Although preliminary, these results support the use of R²I for R/R PCNSL failing conventional chemotherapies.

Classification of evidence: This study provides Class IV evidence that combination of rituximab-lenalidomide-ibrutinib induces a high rate of response in heavily pretreated R/R PCNSL.