Ofatumumab capacity to deplete B cells from chronic lymphocytic leukaemia is affected by C4 complement exhaustion.
The management of patients with chronic lymphocytic leukaemia (CLL) has improved with the utilisation of ofatumumab as a novel anti-CD20 monoclonal antibody. However, as half of the patients fail to respond to the treatment, the aim of this study was to evaluate circulating CLL cell depletion and clinical response according to the context of complement activation and FcγRIIIA polymorphism in ten CLL patients with relapsed/refractory disease. At the end of the treatment, results indicated that circulating CD5(+) CD19(+) CLL cell depletion was major (<0.01 × 10(9) /L) in 4 of 10 patients, partial (>50% decrease) in 4 of 10 patients and ineffective for the two other patients. No clinical modifications were observed following ofatumumab introduction. Ofatumumab administration leads to a rapid and important exhaustion of complement C4 levels in patients with initial lymphocytosis. C4 exhaustion was accelerated in a non-responder patient, and incomplete in two patients with partial circulating depletion. Moreover, delaying weekly to monthly ofatumumab injections improved CLL cell depletion in two patients. FcγRIIIA 158 polymorphism (FF n = 6 and VF n = 4) was not associated with major and/or partial circulating CLL cell depletion. In conclusion, ofatumumab induces an important C4 exhaustion that needs to be taken into account when treating CLL patients with ofatumumab.
Department of Clinical Haematology, Institute of Oncology and Haematology, CHRU morvan, Brest, France.|INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.
Adrian
A
Tempescul
INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.
Cristina
C
Bagacean
Department of Clinical Haematology, Institute of Oncology and Haematology, CHRU morvan, Brest, France.|INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.
Catherine
C
Riou
INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.|Laboratory of Immunology and Immunotherapy, CHRU Morvan, Brest, France.
Boutahar
B
Bendaoud
INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.|Laboratory of Immunology and Immunotherapy, CHRU Morvan, Brest, France.
Sophie
S
Hillion
INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.
Marjolaine
M
Debant
Laboratory of Hematology, CHRU Cavale Blanche, Brest, France.
Caroline
C
Buors
Department of Clinical Haematology, Institute of Oncology and Haematology, CHRU morvan, Brest, France.|INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.
Christian
C
Berthou
INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases, Reseau Epigenetique et Reseau Canaux Ioniques du Cancéropole Grand Ouest, Brest, France.|Laboratory of Immunology and Immunotherapy, CHRU Morvan, Brest, France.
Yves
Y
Renaudineau
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; C496124:FCGR3A protein, human; D017452:Receptors, IgG; C527517:ofatumumab
FcγRIII polymorphism; chronic lymphocytic leukaemia; complement; ofatumumab