Abstract
Loncastuximab tesirine (lonca) is a novel antibody-drug conjugate comprising an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer cytotoxin, indicated for treatment of relapsed/refractory DLBCL after ≥2 systemic treatments.
Characterize the occurrence and management of neutropenia, thrombocytopenia, and anemia in patients with relapsed/refractory DLBCL treated with lonca monotherapy.
Patients with relapsed/refractory DLBCL in the completed phase 1 LOTIS-1 trial (NCT02669017) and the ongoing pivotal phase 2 LOTIS-2 (NCT03589469; data cutoff 06 August 2020) trial received lonca IV every 3 weeks. The LOTIS-1 study used doses ranging from 0.015 to 0.2 mg/kg, while the LOTIS-2 study used the labeled dose of 0.15 mg/kg for 2 doses followed by 0.075 mg/kg for subsequent doses. Growth factor was allowed, according to ASCO guidelines. Incidence of hematologic abnormalities was based on laboratory reporting, while therapy modification was based on adverse event reporting. A pooled safety population of patients treated with an initial dose of 0.15 mg/kg was analyzed.
Grade 3/4 neutropenia occurred in 32.1% (n=69), thrombocytopenia in 20.0% (n=43), and anemia in 12.6% (n=27, all grade 3) of patients. Most patients with grade 3/4 anemia and thrombocytopenia had onset within the first 2 months, by treatment cycle 4. Most patients with grade 3/4 neutropenia had onset within the first 4 months, by treatment cycle 7. Dose delay occurred due to grade 3/4 neutropenia in 10.2% (n=22), grade 3/4 thrombocytopenia in 8.4% (n=18), and grade 3 anemia in 1.4% (n=3) of patients. Dose reduction occurred due to grade 3/4 thrombocytopenia in 0.5% (n=1) of patients and due to grade 3/4 neutropenia in 0.5% (n=1) of patients. No dose reductions occurred due to anemia. Treatment discontinuation occurred due to grade 3/4 thrombocytopenia in 2.3% (n=5) of patients and due to grade 3/4 neutropenia in 0.5% (n=1) of patients. No treatment discontinuations occurred due to anemia. Febrile neutropenia occurred in 3.3% (n=7) of patients.
The incidence of grade ≥3 myelosuppression with lonca was moderate. Most myelosuppression events were manageable with dose delays and did not result in dose reduction or treatment discontinuation.
ADC Therapeutics; medical writing support: CiTRUS Health Group.