title: Comparison of subcutaneous versus intravenous administration of rituximab as maintenance treatment for follicular lymphoma: results from a two-stage, phase IB study.
abstract: OBJECTIVE
  This two-stage phase IB study investigated the pharmacokinetics and safety of subcutaneous (SC) versus intravenous (IV) administration of rituximab as maintenance therapy in follicular lymphoma.
  
  
  METHODS
  In stage 1 (dose finding), 124 patients who responded to rituximab induction were randomly assigned to SC rituximab (375 mg/m2, 625 mg/m2, or an additional group at 800 mg/m2) or IV rituximab (375 mg/m2). The objective was to determine an SC dose that would yield a rituximab serum trough concentration (Ctrough) in the same range as that of IV rituximab. In stage 2, 154 additional patients were randomly assigned (1:1) to SC rituximab (1,400 mg) or IV rituximab (375 mg/m2) given at 2- or 3-month intervals. The objective was to demonstrate noninferior rituximab Ctrough of SC rituximab relative to IV rituximab 375 mg/m2.
  
  
  RESULTS
  Stage 1 data predicted that a fixed dose of 1,400 mg SC rituximab would result in a serum Ctrough in the range of that of IV rituximab. Noninferiority (ie, meeting the prespecified 90% CI lower limit of 0.8) was then confirmed in stage 2, with geometric mean Ctrough SC:Ctrough IV ratios for the 2- and 3-month regimens of 1.24 (90% CI, 1.02 to 1.51) and 1.12 (90% CI, 0.86 to 1.45), respectively. Overall safety profiles were similar between formulations (in stage 2, 79% of patients experienced one or more adverse events in each group). Local administration-related reactions (mainly mild to moderate) occurred more frequently after SC administration.
  
  
  CONCLUSIONS
  The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior Ctrough levels relative to IV rituximab 375 mg/m2 dosing during maintenance, with a comparable safety profile. Additional investigation will be required to determine whether the SC route of administration for rituximab provides equivalent efficacy compared with that of IV administration.
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia. 94131@parcdesalutmar.cat.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Beate
authors.initials: B
authors.lastname: Bittner
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Mike
authors.initials: M
authors.lastname: Brewster
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Catalani
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: George
authors.initials: G
authors.lastname: Follows
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Haynes
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Florence
authors.initials: F
authors.lastname: Hourcade-Potelleret
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Janikova
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Larouche
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Christine
authors.initials: C
authors.lastname: McIntyre
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Juliana
authors.initials: J
authors.lastname: Pereira
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Pakeeza
authors.initials: P
authors.lastname: Sayyed
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.affiliation: Antonio Salar, Hospital del Mar, Barcelona, Spain; Irit Avivi, Rambam Medical Center, Haifa; Ofer Shpilberg, Tel Aviv University, Tel Aviv, Israel; Beate Bittner, Olivier Catalani, Florence Hourcade-Potelleret, and Pakeeza Sayyed, F. Hoffmann-La Roche, Basel, Switzerland; Reda Bouabdallah, Institut Paoli-Calmettes, Marseille, France; Mike Brewster and Christine McIntyre, Roche Products, Welwyn Garden City; George Follows, Addenbrooke's Hospital, University of Cambridge, Cambridge; Andrew Haynes, Nottingham City Hospital, Nottingham, United Kingdom; Andrea Janikova, University Hospital Brno, Brno, Czech Republic; Jean-François Larouche, Hôpital de l'Enfant-Jésus, Centre Hospitalier Universitaire de Québec, Québec, Canada; Michael Pedersen, Herlev Hospital, Herlev, Denmark; Juliana Pereira, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; and Gayane Tumyan, Russian Cancer Research Center, Moscow, Russia.
authors.forename: Gayane
authors.initials: G
authors.lastname: Tumyan
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab