Single-Agent Loncastuximab Induces Response in Patients with DLBCL

A study presented at the 2020 ASH Annual Meeting found that loncastuximab, a humanized anti-CD19 antibody, had substantial single-agent anti-tumor activity in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Adult patients (n=145) with relapsed/refractory DLBCL who failed two or more prior therapies were enrolled in the single-arm, open-label, phase II study. Patients received loncastuximab (mean number of cycles, 4.3; range, 1-15 cycles) and were followed for six or more months from the first dose.

The overall response rate (ORR) was 48.3%, and the complete response (CR) rate was 24.1%. Median duration of response among the 70 patients who responded to loncastuximab was 10.3 months. For patients with a CR, median duration of response was 13.4 months. Most patients responded after two treatment cycles, with a median time to first response of 41 days.

ORR was 44.8% in patients with transformed disease, 45.8% in patients aged 65 to 74 years, and 52.4% in patients aged ≥75 years. For patients with double- or triple-hit DLBCL, ORR was 33.3%, all of which were CRs. Patients who were refractory to first-line therapy, most recent therapy, or any prior therapy had ORRs of 37.9%, 36.9%, and 36.0%, respectively. Patients who had previously undergone hematopoietic cell transplantation (HCT) had an ORR of 58.3%. The ORR was 46.2% in patients who received prior CD19-directed chimeric antigen receptor (CAR) T-cell therapy. Older patients had longer responses to treatment: <65 years, 9.6 months; 65 to 74 years, 10.3 months; and ≥75 years, 13.4 months.

After treatment with loncastuximab, 15 patients received CD19-directed CAR-T therapy; the investigator-assessed ORR was 46.7%, including six CRs and one partial response. Nine patients who responded to loncastuximab went on to receive HCT as consolidation therapy.

Almost all patients (n=143; 98.6%) had at least one treatment-related adverse event (AE), and 105 (72.4%) had grade ≥3 AEs. The most common any-grade AEs were increased gamma-glutamyltransferase (GGT; 40.7%), neutropenia (39.3%), thrombocytopenia (33.1%), fatigue (27.6%), and anemia (26.2%). The most common grade ≥3 AEs were neutropenia (25.5%), thrombocytopenia (17.9%), increased GGT (16.6%), and anemia (10.3%). Twenty-four patients (16.6%) discontinued treatment due to AEs, most commonly due to increased GGT (n=14; 9.7%). Patients aged ≥65 years did not experience more AEs than younger patients.


Caimi PF, Ai WZ, Alderuccio JP, et al. Efficacy and Safety of Loncastuximab Tesirine (ADCT-402) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Abstract 1183. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, December 2-11, 2020.