A phase II 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

Abstract

This phase II, 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 (≥1 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. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 [43.9%; 90% confidence interval (CI:) 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%CI: 3.02-5.78) months, and 9.2 (90%CI: 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 pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887)

New agents and regimens for diffuse large B cell lymphoma

“…The clinical efficacy and safety of SAR3419 monotherapy were evaluated in a phase II multicenter study. Eighteen of 41 patients with r/r DLBCL at dose 55 mg/m 2 obtained ORR (43.9%), with a median DoR of 4.7 months [ 71 ]. Another CD19-targeted ADC ADCT-402 (loncastuximab tesirine) comprising pyrrolobenzodiazepine dimer toxin showed early promise for patients DLBCL.…”

Severe early hepatitis B reactivation in a patient receiving anti-CD19 and anti-CD22 CAR T cells for the treatment of diffuse large B-cell lymphoma

“…Immunotherapy has become one of the most promising treatments for refractory/relapsed B cell lymphoma [1, 2]. Among immunotherapies, chimeric antigen receptor T (CAR T) cell immunotherapy has recently been found to be a highly effective treatment for common pre-B cell acute lymphoblastic leukemia and for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), resulting in approximately a 40% durable response [3–6].…”

Bispecific Antibodies and Antibody–Drug Conjugates for Cancer Therapy: Technological Considerations

“…Moreover, the inherent biological function of CD79b as a component of B-cell receptor (BCR) complex enables the efficient internalization and delivery of the bound ADC to the lysosomes, resulting in highly potent cancer cell killing [83,84]. On the other hand, while CD19 is a prototypical target of B-cell cancers for T cell engaging bsAbs (see above) or CAR-T cells [85] and coltuximab ravtansine (SAR3419, an anti-CD19 ADC) has also been evaluated in clinical trials (NCT01472887) [86], the antigen was found to internalize only in CD21-negative cells [87], exemplifying a technical hurdle of antigen internalization associated with the target selection for ADC.…”