Abstract
Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an FDA-approved antibody drug conjugate (ADC) comprising a CDip-targeted antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer cytotoxin, is indicated in relapsed/refractory diffuse large В-cell lymphoma after >2 prior systemic therapies. Several adverse events (AEs), including edema and effusion, are likely related to the PBD cytotoxin. The objective of this project was to characterize the onset and management of edema and effusion in the pivotal LOTIS-2 trial (NCT03589469). Lonca was administered intravenously every 3 weeks (0.15 mg/ kg for 2 cycles; 0.075 mg/kg for subsequent cycles). Dexamethasone premedication was administered to reduce the incidence and severity of PBD toxicities. Lonca was held for patients with Grade >2 edema/ effusion (as defined by the Common Terminology Criteria for Adverse Events version 4.0) and spironolactone was recommended for initial management of edema or effusion. In this analysis (data cutoff: March 1,2021), missing AE end dates were imputed using the date of new anticancer therapy, end of study, or data cutoff. In LOTIS-2 (N=145), edema occurred in 27.6% of patients; median time to onset was 40.0 days (min, max: 1, 277); and median duration was 50.5 days (2, 676). Grade >3 edema occurred in 3.4% of patients; median time to onset was 106.0 days (9,183); and median duration was 5.0 days (3,112). Effusion occurred in 11.7% of patients; median time to onset was 52.0 days (3, 234); and median duration was 20.0 days (4, 581). Grade >3 effusion occurred in 2.8% of patients; median time to onset was 118.0 days (17,277); and median duration was 20.5 days (6, 411). In the total trial population, dose delays, reductions, and withdrawal occurred due to edema in 4.8%, 0.7%, and 2.8% of patients, respectively, and due to effusion in 1.4%, 0%, and 2.8% of patients, respectively. The median time to onset of any grade edema and effusion was approximately 2 and 3 treatment cycles, respectively. Incidence of Grade >3 edema and effusion was low and typically occurred later in therapy, with a median time to onset of approximately 6 treatment cycles. Edema and effusion were generally manageable with dose delays and modifications, which are recommended for Grade >2 events.