title: Pharmacokinetics and tolerability of human mouse chimeric anti-CD22 monoclonal antibody in Chinese patients with CD22-positive non-Hodgkin lymphoma.
abstract: The safety and pharmacokinetics assessment of antibodies targeting CD22 (e.g., epratuzumab) have been established in western Caucasian populations, but there are no reports of the effects in Chinese populations. This dose-escalation study examines the safety, pharmacokinetics and biologic effects of multiple doses of anti-CD22 human-murine chimeric monoclonal antibody SM03 in 21 Chinese patients with CD22-positive non-Hodgkin lymphoma. Most of drug-related adverse events (AEs) were mild and reversible. Two patients experienced serious AEs (hemorrhage); one patient had grade 4 neutropenia; one patient had asymptomatic grade III prolongation of activated partial thromboplastin time (APTT). Major AEs included fever (71%), prolongation of APTT (42.8%), leukocytopenia (44.4%), alanine transaminase elevation (28.6%), elevated serum creatinine (23.8%) and injection site skin redness (14.3%). Circulating B cells transiently decreased without significant effects on T cells or immunoglobulin levels. Pharmacokinetic data revealed that mean maximum observed SM03 concentration and mean AUC from time zero to infinity increased in a dose-dependent manner up to 360 mg/m (2) SM03. Mean clearance was similar at doses ≤ 360 mg/m (2) and decreased significantly at dose 480 mg/m (2), supporting saturation of B-cell binding at 360 mg/m (2). Across all dose levels and histologies, one patient achieved partial response at 480 mg/m (2) dose; 14 patients had stable disease as best response and four patients progressed. Overall, SM03 was tolerated at doses ranging from 60-480 mg/m (2) and had potential efficacy in Chinese patients with follicular lymphoma.
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Clinical Trial Center; Cancer Center; Sun Yat-sen University; Guangzhou, Guangdong, China.
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Medical Oncology; Cancer Center; Sun Yat-Sen University; Guangzhou, Guangdong, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Clinical Trial Center; Cancer Center; Sun Yat-sen University; Guangzhou, Guangdong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Medical Oncology; Cancer Center; Sun Yat-Sen University; Guangzhou, Guangdong, China.
authors.forename: Zhinming
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Clinical Trial Center; Cancer Center; Sun Yat-sen University; Guangzhou, Guangdong, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Medical Oncology; Cancer Center; Sun Yat-Sen University; Guangzhou, Guangdong, China.
authors.forename: Benyan
authors.initials: B
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Clinical Trial Center; Cancer Center; Sun Yat-sen University; Guangzhou, Guangdong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Oncology in Southern China; Sun Yat-Sen University; Guangzhou, Guangdong, China; Department of Medical Oncology; Cancer Center; Sun Yat-Sen University; Guangzhou, Guangdong, China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics*; D002681:China; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D051918:Sialic Acid Binding Ig-like Lectin 2
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D051918:Sialic Acid Binding Ig-like Lectin 2