Phase I clinical study of atacicept in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma

Stephen M. Ansell, Thomas E. Witzig, David J. Inwards, Luis F. Porrata, Arnaud Ythier, Lee Ferrande, Ivan Nestorov, Todd DeVries, Stacey R. Dillon, Diana Hausman, Anne J. Novak

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Purpose: B-lymphocyte stimulator and a proliferation-inducing ligand regulate B-cell homeostasis and immunoglobulin production and are overexpressed in B-cell malignancies. Atacicept (TACI-Ig), a recombinant fusion protein that inhibits both B-lymphocyte stimulator and a proliferation-inducing ligand, may be a novel treatment for B-cell malignancies. Experimental Design: A phase 1, open-label, dose-escalation study of atacicept in patients with relapsed or refractory B-cell lymphoma was done. Atacicept was given s.c. weekly for 5 weeks to sequential patient cohorts at doses of 2, 4,7, or10 mg/kg. Patients responding or with stable disease were eligible for treatment on an extension study for up to 24 weeks or until disease progression. Results: All patients were heavily pretreated (median number of previous treatments, 5; range, 1-10), and four patients had previously received a stem cell transplant. Four patients were treated at the 2, 4, or 7 mg/kg dose levels, and three patients received 10 mg/kg of atacicept. Atacicept was well tolerated at all doses. Three adverse events with grade 3 severity were reported for one patient, including jaw pain, gastrointestinal hemorrhage, and sepsis; all were considered unrelated to atacicept. Pharmacokinetic results were nonlinear, and treatment with atacicept resulted in dose-dependent decreases in immunoglobulin concentrations. Two patients had stable disease at 8 weeks, entered the extension study, and received additional doses of atacicept with no safety or tolerability concerns. Conclusion: Atacicept at doses of up to 10 mg/kg was well tolerated and showed biological activity by decreasing immunoglobulin concentrations, although tumor responses were not observed.

Original languageEnglish (US)
Pages (from-to)1105-1110
Number of pages6
JournalClinical Cancer Research
Volume14
Issue number4
DOIs
StatePublished - Feb 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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