A Phase 2 multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy

This phase 2, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥ lesion >5 cm) at trial entry. Patients received coltuximab ravtansine (55 mg/m2) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. 41 patients were eligible for inclusion in the per-protocol population. The primary endpoint, overall response rate (International Working Group criteria) in the per-protocol population, was 18/41 (43.9% [90% confidence interval 30.6-57.9%]). Median duration of response, progression-free survival and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90% confidence interval 3.02-5.78) months, and 9.2 (90% confidence interval 6.57-12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. ClinicalTrials.gov trial identifier: NCT01472887.