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

Neurology. 2021 Sep 28;97(13):628-631. doi: 10.1212/WNL.0000000000012515.

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.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Female
  • Humans
  • Lenalidomide / administration & dosage*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Piperidines / administration & dosage*
  • Retrospective Studies
  • Rituximab / administration & dosage*

Substances

  • Piperidines
  • ibrutinib
  • Rituximab
  • Lenalidomide
  • Adenine