Blood Journal
Leading the way in experimental and clinical research in hematology

Multicenter phase I trial of intraventricular immuno-chemotherapy in recurrent CNS lymphoma

  1. James L. Rubenstein1,*,
  2. Jing Li2,
  3. Lingjing Chen1,
  4. Ranjana Advani3,
  5. Jan Drappatz4,
  6. Elizabeth Gerstner5,
  7. Tracy Batchelor5,
  8. Hendrikus Krouwer6,
  9. James Hwang7,
  10. Glenna Auerback8,
  11. Cigall Kadoch1,
  12. Clifford Lowell9,
  13. Pamela Munster8,
  14. Soonmee Cha10,
  15. Marc A. Shuman1, and
  16. Lloyd E. Damon1
  1. 1 Division of Hematology/Oncology, University of California, San Francisco, CA, United States;
  2. 2 Genentech, South San Francisco, CA, United States;
  3. 3 Medical Oncology, Stanford University, Stanford, CA, United States;
  4. 4 Neuro-oncology, Dana Farber Cancer Center, Boston, MA, United States;
  5. 5 Neuro-oncology, Massachusetts General Hospital, Boston, MA, United States;
  6. 6 Neuro-oncology, Medical College of Wisconsin, Waukesha, WI, United States;
  7. 7 Biostatistics and Computational Biology Core, University of California, San Francisco, CA, United States;
  8. 8 Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, United States;
  9. 9 Laboratory Medicine, University of California, San Francisco, CA, United States;
  10. 10 Department of Radiology, University of California, San Francisco, CA, United States
  1. * Corresponding author; email: jamesr{at}medicine.ucsf.edu

Abstract

Recurrent CNS lymphoma continues to be associated with poor outcomes in the rituximab era. Although intravenous administration of rituximab mediates superior disease control of systemic non-Hodgkin's lymphoma (NHL), it fails to completely eliminate the risk of meningeal recurrence, likely because of minimal CNS penetration. Given that rituximab acts synergistically with chemotherapy in systemic lymphoma, we conducted the first phase I study of intraventricular immuno-chemotherapy in patients with recurrent CNS NHL. Fourteen patients received 10 mg (N=3) or 25 mg (N=11) intraventricular rituximab twice-weekly over four weeks, with rituximab administered as monotherapy during the first treatment each week and rituximab administered in combination with methotrexate (12 mg) during the second treatment each week. Greater than 150 doses were administered without serious toxicity. In a population with NHL refractory to a median of five prior therapies, 75% of patients achieved complete cytologic cerebrospinal fluid (CSF) responses and 43% of patients achieved an overall complete response (CR) in CSF and/or brain parenchyma. Two patients achieved a first CR of CNS NHL with intraventricular rituximab/methotrexate, including one with CNS lymphoma refractory to high-dose systemic and intrathecal methotrexate plus intravenous rituximab. Intraventricular rituximab in combination with methotrexate is feasible and highly active in the treatment of drug-resistant CNS NHL, refractory or non-responsive to intravenous rituximab. Registered at clinicaltrials.gov: NCT00221325.

  • Submitted July 5, 2012.
  • Accepted November 4, 2012.