A phase II, single-arm, multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma.
British journal of haematology
Membres identifiés du Cancéropôle Est :
Dr CASASNOVAS Olivier
Tous les auteurs :
Coiffier B, Thieblemont C, de Guibert S, Dupuis J, Ribrag V, Bouabdallah R, Morschhauser F, Navarro R, Le Gouill S, Haioun C, Houot R, Casasnovas O, Holte H, Lamy T, Broussais F, Payrard S, Hatteville L, Tilly H
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.
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, administration & dosage, Antineoplastic Combined Chemotherapy Protocols, therapeutic use, Asthenia, chemically induced, Drug Administration Schedule, Female, Gastrointestinal Diseases, chemically induced, Humans, Lymphoma, Large B-Cell, Diffuse, complications, Male, Maytansine, administration & dosage, Middle Aged, Recurrence, Rituximab, administration & dosage, Salvage Therapy, methods, Survival Analysis, Treatment Outcome
Br. J. Haematol.. 2016 06;173(5):722-30