title: A phase II, single-arm, multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma.
abstract: In this phase II, multicentre, single-arm study, 52 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) received the anti-CD19 antibody-drug conjugate coltuximab ravtansine (55 mg/m(2) ) and rituximab (375 mg/m(2) ) weekly for 4 weeks, then every 2 weeks for 8 weeks. The primary endpoint was objective response rate (ORR) by International Working Group Criteria. The primary objective was to reject the null hypothesis of an ORR of ≤40%. Among 45 evaluable patients, the ORR was 31·1% (80% confidence interval [CI]: 22·0-41·6%) and the primary objective was not met. The ORR appeared higher in patients with relapsed disease (58·3% [80% CI: 36·2-78·1%]) versus those refractory to their last (42·9% [80% CI: 17·0-72·1%]) or first-line therapy (15·4% [80% CI: 6·9-28·4%]). Median progression-free survival, overall survival and duration of response were 3·9 [80% CI: 3·22-3·98], 9·0 [80% CI: 6·47-13·67] and 8·6 (range: 0-18) months, respectively. The pharmacokinetics of both drugs were unaffected by co-administration. Common adverse events included gastrointestinal disorders (52%) and asthenia (25%). No patients discontinued due to adverse events. In conclusion, coltuximab ravtansine with rituximab was well tolerated and yielded clinical responses in a subset of patients with relapsed/refractory DLBCL.
authors.affiliation: Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.affiliation: Department of Hemato-oncology - Paris Diderot 7 University, APHP - Hôpital Saint-Louis, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.affiliation: CHU de Rennes, Rennes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: de Guibert
authors.affiliation: Hopital Henri Mondor, Créteil, France.
authors.forename: Jehan
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.affiliation: Institut Paoli Calmettes, Marseille, France.
authors.forename: Réda
authors.initials: R
authors.lastname: Bouabdallah
authors.affiliation: CHRU - Hôpital Claude Huriez, Lille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
authors.affiliation: CHU Saint Eloi, Montpellier, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Navarro
authors.affiliation: CHU Hôtel Dieu, Nantes, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.affiliation: Hopital Henri Mondor, Créteil, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.affiliation: CHU de Rennes, Rennes, France.
authors.forename: Roch
authors.initials: R
authors.lastname: Houot
authors.affiliation: CHU Le Bocage, Dijon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Casasnovas
authors.affiliation: Oslo University Hospital, Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.affiliation: CHU de Rennes, Rennes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.affiliation: Institut Paoli Calmettes, Marseille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Broussais
authors.affiliation: Sanofi, Vitry-sur-Seine, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Payrard
authors.affiliation: Sanofi, Vitry-sur-Seine, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Hatteville
authors.affiliation: Centre Henri Becquerel, UMR918, Université de Rouen, Rouen, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008453:Maytansine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D008875:Middle Aged; D012008:Recurrence; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D008453:Maytansine; D000069283:Rituximab; C569646:coltuximab ravtansine
keywords: CD19; antibody-drug conjugate; lymphoma; maytansinoid; resistance