A phase II, single-arm, multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma

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 (55mg/m(2)) and rituximab (375mg/m(2)) weekly for 4weeks, then every 2weeks for 8weeks. 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 311% (80% confidence interval [CI]: 220-416%) and the primary objective was not met. The ORR appeared higher in patients with relapsed disease (583% [80% CI: 362-781%]) versus those refractory to their last (429% [80% CI: 170-721%]) or first-line therapy (154% [80% CI: 69-284%]). Median progression-free survival, overall survival and duration of response were 39 [80% CI: 322-398], 90 [80% CI: 647-1367] and 86 (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.