A phase II,single‐arm,multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B‐cell lymphoma |
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| Authors: | Bertrand Coiffier Catherine Thieblemont Sophie de Guibert Jehan Dupuis Vincent Ribrag Réda Bouabdallah Franck Morschhauser Robert Navarro Steven Le Gouill Corinne Haioun Roch Houot Olivier Casasnovas Harald Holte Thierry Lamy Florence Broussais Sandrine Payrard Laurence Hatteville Hervé Tilly |
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| Affiliation: | 1. Centre Hospitalier Lyon Sud, Pierre Bénite, France;2. Department of Hemato‐oncology – Paris Diderot 7 University, APHP – H?pital Saint‐Louis, Paris, France;3. CHU de Rennes, Rennes, France;4. Hopital Henri Mondor, Créteil, France;5. Institut Gustave Roussy, Villejuif, France;6. Institut Paoli Calmettes, Marseille, France;7. CHRU – H?pital Claude Huriez, Lille, France;8. CHU Saint Eloi, Montpellier, France;9. CHU H?tel Dieu, Nantes, France;10. CHU Le Bocage, Dijon, France;11. Oslo University Hospital, Oslo, Norway;12. Sanofi, Vitry‐sur‐Seine, France;13. Centre Henri Becquerel, UMR918, Université de Rouen, Rouen, France |
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| 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/m2) and rituximab (375 mg/m2) 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. |
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| Keywords: | maytansinoid lymphoma resistance antibody– drug conjugate CD19 |
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