PCNSL

ASCO® 2016: Lenalidomide as Maintenance for Recurrent/Refractory CNS Lymphoma Yields Promising Results in Phase I study

This ASCO 2016 oral abstract presentation took place on Sunday June 5, 9:45am–12:45pm, during the ‘Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia’ session. This session was chaired by Pr Gilles Salles, Head of the Hematology Department in South Lyon hospitals, Lyon, France.

The presentation of this abstract (#7502was given by Dr James L Rubenstein, Professor of Medicine at the University of California, San Francisco.

Currently, for relapsed CNS lymphoma, there is a lack of effective biological agents. Lenalidomide (CC-5013) has been shown to have activity in Activated B-Cell Like-DLBCL and so a phase I study (NCT01542918) investigating lenalidomide plus rituximab for the treatment of R/R CNS and Intraocular Lymphoma was initiated.

The primary outcome measure was to establish the maximal tolerated dose of lenalidomide (10, 20, or 30mg) in patients, who were followed for the duration of the treatment (an expected average of 4 months). Secondary endpoints were to determine: Cerebrospinal Fluid (CSF) penetration of lenalidomide; feasibility of intraventricular plus intravenous rituximab; and Time to Progression (TTP) of maintenance lenalidomide in an independent cohort of relapsed CNS NHL patients.

Inclusion criteria included age ≥18 years, CD20+ lymphoma on previous analysis, and an absolute neutrophil count of >1,500 (growth factors permitted).

  • Treated on the phase I protocol = 13 subjects with refractory CNS DLBCL (8 PCNSL, 5 SCNSL)
  • Median age = 63 years (range, 46-78)
  • With lenalidomide monotherapy: 3 CRs, 1 PR in brain parenchymal NHL; 2 CR of CSF NHL; 1 CR, 2 PR’s of intraocular NHL
  • Four maintained CR to lenalidomide >9 months and 2 >1.8 years
  • Independent cohort = 12 pts with recurrent CNS DLBCL (10 PCNSL, 2 SCNSL; median age = 70 years; range, 59–81) received lenalidomide monotherapy (5–10mg) as maintenance after salvage
  • Median follow-up of >18 months
  • TTP: 5 pts maintained remissions for >2 years
  • Among 10 CNS DLBCL pts with multiple CNS relapses that received focal XRT or HD-MTX-rituximab salvage, followed by lenalidomide maintenance, TTP at CR 2-4 was >5 times longer than TTP in these pts after standard induction and consolidation chemotherapy, without lenalidomide (< 0.013; HR, 3.75)
  • Trough lenalidomide concentration in ventricular CSF was highest at 20mg dose
  • Elevated CSF lactate predicted short PFS (< 0.01)
  • Responses observed at each dose level tested and in 9/13 evaluable pts
  • Recommended lenalidomide starting dose = 15mg/d on 21 day cycle

It was found that maintenance with lenalidomide at modest doses was feasible and resulted in improved PFS in patients with R/R CNS lymphoma; it may delay or even completely remove the need for whole brain radiotherapy. Moreover, lenalidomide demonstrated the potential to be combined with focal irradiation, either radiosurgery or involved field radiation. This study presents some of the first emerging evidence in support of using lenalidomide as maintenance therapy; it significantly improved TTP after salvage in relapsed CNS DLBCL and delayed whole brain radiotherapy. Additionally, minimal sife effects were observed with lenalidomide (one non-invasive Basal Cell Carcinoma reported). However, further prospective clinical trials are required to confirm the efficacy and safety of immunomodulatory imide drugs for this patient population.

Reference

1. Rubenstein JL, et al. Phase I investigation of lenalidomide plus rituximab and outcomes of lenalidomide maintenance in recurrent CNS Lymphoma. J Clin Oncol 34, 2016 (suppl; abstr 7502).