Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma

Stephen M. Ansell, Sara A. Hurvitz, Patricia A. Koenig, Betsy R. LaPlant, Brian F. Kabat, Donna Fernando, Thomas M. Habermann, David J. Inwards, Meena Verma, Reiko Yamada, Charles Erlichman, Israel Lowy, John M. Timmerman

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

Purpose: The growth of non-Hodgkin lymphomas can be influenced by tumor-immune system interactions. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative regulator of T-cell activation that serves to dampen antitumor immune responses. Blocking anti-CTLA-4 monoclonal antibodies improves host resistance to immunogenic tumors, and the anti-CTLA-4 antibody ipilimumab (MDX-010) has clinical activity against melanoma, prostate, and ovarian cancers. Experimental Design: We did a phase I trial of ipilimumabi n patients with relapsed/refractory B-cell lymphoma to evaluate safety, immunologic activity, and potential clinical efficacy. Treatment consisted of ipilimumabat 3 mg/kg and then monthly at 1 mg/kg x 3 months (dose level 1), with subsequent escalation to 3 mg/kg monthly x 4 months (dose level 2). Results: Eighteen patients were treated, 12 at the lower dose level and 6 at the higher dose level. Ipilimumabwas generally well tolerated, with common adverse events attributed to it, including diarrhea, headache, abdominal pain, anorexia, fatigue, neutropenia, and thrombocytopenia. Two patients had clinical responses; one patient with diffuse large B-cell lymphoma had an ongoing complete response (>31 months), and one with follicular lymphoma had a partial response lasting 19 months. In 5 of 16 cases tested (31%), T-cell proliferation to recall antigens was significantly increased (>2-fold) after ipilimumab therapy. Conclusions: Blockade of CTLA-4 signaling with the use of ipilimumabis well tolerated at the doses used and has antitumor activity in patients with B-cell lymphoma. Further evaluation of ipilimumab alone or in combination with other agents in B-cell lymphoma patients is therefore warranted.

Original languageEnglish (US)
Pages (from-to)6446-6453
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number20
DOIs
StatePublished - Oct 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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