Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics.
The anti-CD20 antibody rituximab (RTX; Rituxan®, MabThera®) was the first anti-cancer antibody approved by the US Food and Drug Administration in 1997 and it is now the most-studied unconjugated therapeutic antibody. The knowledge gained over the past 15 y on the pharmacodynamics (PD) of this antibody has led to the development of a new generation of anti-CD20 antibodies with enhanced efficacy in vitro. Studies on the pharmacokinetics (PK) properties and the effect of factors such as tumor load and localization, antibody concentration in the circulation and gender on both PK and clinical response has allowed the design of optimized schedules and novel routes of RTX administration. Although clinical results using newer anti-CD20 antibodies, such as ofatumumab and obinutuzumab, and novel administration schedules for RTX are still being evaluated, the knowledge gained so far on RTX PK and PD should also be relevant for other unconjugated monoclonal antibody therapeutics, and will be critically reviewed here.
Division of Hematology; Ospedale Papa Giovanni XXIII; Bergamo, Italy.
Josée
J
Golay
Padua University School of Medicine; Hematology Branch; Department of Medicine; Padua, Italy.
Gianpietro
G
Semenzato
Division of Hematology; Ospedale Papa Giovanni XXIII; Bergamo, Italy.
Alessandro
A
Rambaldi
Division of Hematology; Department of Cellular Biotechnologies and Hematology; University "Sapienza"; Rome, Italy.
Robin
R
Foà
Division of Hematology; Department of Translational Medicine; Amedeo Avogadro University of Eastern Piedmont; Novara, Italy.
Gianluca
G
Gaidano
Roche Italia SpA; Monza, Italy.
Enrica
E
Gamba
Dipartimento di Medicina Clinica e Chirurgia; Università di Napoli Federico II and Ceinge-Biotecnologie Avanzate; Naples, Italy.
Fabrizio
F
Pane
Hematology-Oncology and Stem Cell Transplantation Unit; Istituto Nazionale Tumori; Fondazione 'G.Pascale'; IRCCS; Naples, Italy.
Antonello
A
Pinto
Hematology Section, University of Bari, Italy.
Giorgina
G
Specchia
Clinica Ematologica; DISM, AOUD S.M. Misericordia; Udine, Italy.
Francesco
F
Zaja
IRCCS Policlinico San Matteo; Pavia, Italy.
Mario
M
Regazzi
D058846:Antibodies, Monoclonal, Murine-Derived / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy; D011485:Protein Binding; D000069283:Rituximab; D012737:Sex Factors
D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab
B-NHL; CLL; FcRn; FcγRs; pharmacodynamics; pharmacokinetics; rituximab