Omalizumab and the risk of malignancy: Results from a pooled analysis

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 4; pp. 983 - 989.e6
• Main Authors: Busse, William, Buhl, Roland, Fernandez Vidaurre, Carlos, Blogg, Martin, Zhu, Jin, Eisner, Mark D., Canvin, Janice
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2012; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allergies; allergy; Allergy and Immunology; Anti-Asthmatic Agents - adverse effects; anti-IgE; Antibodies, Anti-Idiotypic - adverse effects; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized - adverse effects; Asthma; Biological and medical sciences; Child; Child, Preschool; Chronic obstructive pulmonary disease, asthma; Clinical trials; Data processing; Drug therapy; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histology; Humans; IgE; Immunoglobulin E; Immunology; Immunopathology; Incidence; Male; Malignancy; Medical sciences; Middle Aged; Monoclonal antibodies; Neoplasms - epidemiology; Neoplasms - etiology; Omalizumab; Organs; patients; Pharmaceutical industry; Pneumology; pooled analysis; Risk; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Studies; therapeutics; Young Adult; RDBPC; anti-IgE; pooled analysis; malignancy; AE; IgE; allergy; omalizumab; NMSC; Asthma; Nonmelanoma skin cancer; Adverse event; Randomized, double-blind, placebo-controlled; Lung disease; Allergy; Immunopathology; Respiratory disease; Omalizumab; Risk; Malignancy; Monoclonal antibody; Malignant tumor; Immunology; Risk factor; Bronchus disease; Obstructive pulmonary disease; Cancer
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.01.033

Since initial registration, the omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%). The previous analysis was based on limited available data, warranting further investigation. We sought to examine the incidence of malignancy using comprehensive pooled data from clinical trials of omalizumab-treated patients. This pooled analysis included data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, double-blind, placebo-controlled (RDBPC) trials. There were 11,459 unique patients in all clinical trials (7,789 received omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for omalizumab- and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. In this pooled analysis no association was observed between omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between omalizumab therapy and malignancy is unlikely.