A Phase 1b 2 trial of mapatumumab in patients with relapsed refractory non-Hodgkin's lymphoma

• Published in: British journal of cancer 2010-12, Vol.103 (12), p.1783-1787
• Main Authors: Younes, A, Vose, J M, Zelenetz, A D, Smith, M R, Burris, H A, Ansell, S M, Klein, J, Halpern, W, Miceli, R, Kumm, E, Fox, N L, Czuczman, M S
• Format: Article
• Language: English
• Subjects: 631/92/436/108; 692/699/67/1990/291/1621; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical Study; Drug Resistance; Epidemiology; Female; Humans; Lymphoma, Non-Hodgkin - drug therapy; Male; Middle Aged; Molecular Medicine; Oncology; Receptors, TNF-Related Apoptosis-Inducing Ligand - analysis; Receptors, TNF-Related Apoptosis-Inducing Ligand - antagonists & inhibitors; Recurrence
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605987

Background: We conducted a multicentre Phase 1b/2 trial to evaluate the safety and efficacy of mapatumumab, a fully human agonistic monoclonal antibody to the tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) in patients with relapsed non-Hodgkin's lymphoma (NHL). Methods: Forty patients with relapsed or refractory NHL were treated with either 3 or 10 mg kg −1 mapatumumab every 21 days. In the absence of disease progression or prohibitive toxicity, patients received a maximum of six doses. Results: Mapatumumab was well tolerated, with no patients experiencing drug-related hepatic or other dose-limiting toxicity. Three patients with follicular lymphoma (FL) experienced clinical responses, including two with a complete response and one with a partial response. Immunohistochemistry staining of the TRAIL-R1 suggested that strong staining in tumour specimens did not appear to be a requirement for mapatumumab activity in FL. Conclusions: Mapatumumab is safe and has promising clinical activity in patients with FL.