Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in patients with relapsed/refractory follicular lymphoma.
BACKGROUND
Ocrelizumab is a humanized anti-CD20 antibody with increased antibody-dependent cellular cytotoxicity compared with rituximab. This phase I/II study evaluated its safety and efficacy in patients with relapsed/refractory follicular lymphoma (FL) after prior rituximab therapy.


METHODS
Forty-seven patients were treated in three dose cohorts and received eight infusions every 3 weeks: cohort A, 200 mg/m(2) (n = 15); cohort B, 375 mg/m(2) (n = 16); cohort C, first dose 375 mg/m(2), seven subsequent doses of 750 mg/m(2) (n = 16). Patients were assessed for safety, efficacy, pharmacodynamics and pharmacokinetics.


RESULTS
The median patient age was 58 years, the majority had Ann Arbor stage III/IV disease and had received a median of 2 (range 1-6) prior regimens. Ocrelizumab was well tolerated with grade 3/4 toxicity occurring in 9% of patients. The most common toxicity was infusion-related reactions (74% patients), all grade 1/2 except one grade 3 event. The objective response rate was 38% and was similar in patients with low-affinity and high-affinity variants of the Fcgamma receptor IIIa (FcgammaRIIIa). With follow-up of approximately 28 months, the median progression-free survival was 11.4 months.


CONCLUSIONS
Ocrelizumab demonstrated activity in patients with relapsed/refractory FL following prior rituximab treatment, with safety similar to rituximab although adverse events appeared milder.
Department of Hematology, Claude Huriez Hospital, Lille, France. Electronic address: franck.morschhauser@chru-lille.fr.
F
F
Morschhauser
Department of Clinical Hematology and Medical Oncology, Princess Alexandra Hospital, Brisbane, Australia.
P
P
Marlton
Department of Hematology, San Giovanni Battista Hospital, Turin, Italy.
U
U
Vitolo
Department of Oncology, Lund University Hospital, Lund, Sweden.
O
O
Lindén
Department of Hematology and Medical Oncology, Peter MacCallum Cancer Institute and University of Melbourne, Victoria, Australia.
J F
JF
Seymour
Department of Medical Oncology, Princess Margaret Hospital, Toronto, Canada.
M
M
Crump
Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre Bénite, France.
B
B
Coiffier
Department of Cellular Biotechnologies and Hematology, 'Sapienza University', Rome, Italy.
R
R
Foà
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
E
E
Wassner
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
H-U
HU
Burger
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
B
B
Brennan
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
M
M
Mendila
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; C533411:ocrelizumab