Brief Communication: Rituximab in HIV-Associated Multicentric Castleman Disease

  1. Mark Bower, PhD;
  2. Tom Powles, MD;
  3. Sarah Williams, MB;
  4. Tom Newsom Davis, PhD;
  5. Mark Atkins, PhD;
  6. Silvia Montoto, MD;
  7. Chloe Orkin, MD;
  8. Andy Webb, PhD;
  9. Martin Fisher, BSc;
  10. Mark Nelson, MA;
  11. Brian Gazzard, MD;
  12. Justin Stebbing, PhD; and
  13. Peter Kelleher, PhD
  1. From Imperial College, The Chelsea and Westminster Hospital, Barts and the London NHS Trust, and Queen Mary's University, London, and Royal Sussex Country Hospital, Brighton, United Kingdom.

    Abstract

    Background: HIV-associated multicentric Castleman disease is a rare lymphoproliferative disorder with marked systemic symptoms attributed to cytokine disarray. Many therapeutic approaches in small series of patients have proved largely unsuccessful to date.

    Objective: To investigate the efficacy and clinicopathologic variables associated with first-line treatment for HIV-associated multicentric Castleman disease with the anti-CD20 monoclonal antibody rituximab.

    Design: Single-group, open-label, phase II trial.

    Setting: 3 teaching hospitals in England.

    Patients: Previously untreated patients with histologically proven HIV-associated multicentric Castleman disease.

    Intervention: 4 infusions of rituximab, 375 mg per m2 of body surface area, at weekly intervals.

    Measurements: Response was evaluated clinically and radiologically and by measuring plasma Kaposi sarcoma–associated herpesvirus viral load.

    Results: 21 consecutive patients (18 men) with plasmablastic multicentric Castleman disease were recruited. The median follow-up was 12 months (range, 1 to 49 months). One patient died before completing therapy, 20 achieved remission of symptoms, and 14 (67%) achieved a radiologic response. The overall and disease-free survival rates at 2 years were 95% (95% CI, 86% to 100%) and 79% (CI, 49% to 100%), respectively. Plasma acute-phase proteins, immunoglobulins, and Kaposi sarcoma–associated herpesvirus viral load decreased after rituximab therapy. The main adverse effect was reactivation of Kaposi sarcoma.

    Limitation: The study had no comparison group.

    Conclusion: Rituximab may be clinically valuable as initial therapy for HIV-associated multicentric Castleman disease.

    Article and Author Information

    • Financial Support: Support for the cytokine assays was provided by St. Stephen's AIDS Trust, a national charity supporting clinical research in HIV/AIDS.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Mark Bower, PhD, Department of Oncology, The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom; e-mail, m.bower{at}imperial.ac.uk.

    • Current Author Addresses: Drs. Bower, Newsom Davis, Atkins, and Gazzard; Ms. Williams; and Mr. Nelson: The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom.

    • Drs. Powles, Montoto, and Orkin: St. Bartholomew's Hospital, Little Brittain, London EC1 7BE, United Kingdom.

    • Dr. Webb and Mr. Fisher: Royal Sussex County Hospital, Eastern Road, Brighton BN1 3RP, United Kingdom.

    • Drs. Stebbing and Kelleher: Imperial College School of Medicine, 369 Fulham Road, London SW10 9NH, United Kingdom.

    • Author Contributions: Conception and design: M. Bower, T. Powles, T. Newsom Davis, C. Orkin, M. Nelson, B. Gazzard, J. Stebbing, P. Kelleher.

    • Analysis and interpretation of the data: M. Bower, T. Powles, S. Williams, T. Newsom Davis, S. Montoto, J. Stebbing, P. Kelleher.

    • Drafting of the article: M. Bower, T. Powles, S. Montoto, J. Stebbing, P. Kelleher.

    • Critical revision of the article for important intellectual content: M. Bower, T. Powles, M. Atkins, S. Montoto, A. Webb, M. Fisher, M. Nelson, J. Stebbing, P. Kelleher.

    • Final approval of the article: M. Bower, T. Powles, S. Williams, T. Newsom Davis, S. Montoto, C. Orkin, A. Webb, M. Fisher, M. Nelson, B. Gazzard, J. Stebbing.

    • Provision of study materials or patients: M. Bower, M. Atkins, S. Montoto, C. Orkin, A. Webb, M. Fisher, M. Nelson, P. Kelleher.

    • Statistical expertise: M. Bower, J. Stebbing.

    • Obtaining of funding: M. Nelson, B. Gazzard, P. Kelleher.

    • Administrative, technical, or logistic support: M. Bower, B. Gazzard, P. Kelleher.

    • Collection and assembly of data: M. Bower, M. Atkins, A. Webb, M. Fisher, J. Stebbing, P. Kelleher.

    Responses to this article

    • Rituximab in HIV-Associated Multicentric Castleman Disease
      • Raphael Stricker
      Ann Intern Med published online October 26, 2009
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