Faculty Collaboration Database

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood 2021 May 13;137(19):2634-2645

Date

11/20/2020

Pubmed ID

33211842

Pubmed Central ID

PMC8138546

DOI

10.1182/blood.2020007512

Scopus ID

2-s2.0-85106521180 (requires institutional sign-in at Scopus site)   102 Citations

Abstract

The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a phase 1 dose-escalation and dose-expansion study in patients with R/R B-NHL. Objectives were to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion and evaluate safety, clinical activity, pharmacokinetics, and immunogenicity of loncastuximab tesirine. Overall, 183 patients received loncastuximab tesirine, with 3 + 3 dose escalation at 15 to 200 µg/kg and dose expansion at 120 and 150 µg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 µg/kg. Hematologic treatment-emergent adverse events were most common, followed by fatigue, nausea, edema, and liver enzyme abnormalities. Overall response rate (ORR) in evaluable patients was 45.6%, including 26.7% complete responses (CRs). ORRs in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and follicular lymphoma were 42.3%, 46.7%, and 78.6%, respectively. Median duration of response in all patients was 5.4 months and not reached in patients with DLBCL (doses ≥120 µg/kg) who achieved a CR. Loncastuximab tesirine had good stability in serum, notable antitumor activity, and an acceptable safety profile, warranting continued study in B-NHL. The recommended dose for phase 2 was determined as 150 µg/kg every 3 weeks for 2 doses followed by 75 µg/kg every 3 weeks. This trial was registered at www.clinicaltrials.gov as #NCT02669017.

Author List

Hamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid E, O'Connor OA, Feingold JM, Ardeshna KM, Townsend W, Solh M, Heffner LT, Ungar D, Wang L, Boni J, Havenith K, Qin Y, Kahl BS

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Benzodiazepines
Febrile Neutropenia
Female
Humans
Immunotoxins
Lymphoma, B-Cell
Male
Middle Aged
Recurrence
Salvage Therapy
Thrombocytopenia
Young Adult