In relapsed or refractory diffuse large B-cell lymphoma, CD19 expression by immunohistochemistry alone is not a predictor of response to loncastuximab tesirine.

CD19-targeting treatments have shown promise in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]) is a CD19-targeting antibody-drug conjugate indicated for R/R DLBCL after at least two systemic treatments. CD19 expression was evaluated in patients receiving Lonca in the LOTIS-2 clinical trial with available tissue samples obtained after last systemic therapy/before Lonca treatment. Lonca cytotoxicity was evaluated in a panel of six lymphoma cell lines with various CD19 expression levels. Quantitative systems pharmacology (QSP) modelling was used to predict Lonca responses. Lonca responses were seen in patients across all CD19 expression levels, including patients with low/no detectable CD19 expression and H-scores at baseline. Similarly, Lonca induced cytotoxicity in cell lines with different levels of CD19 expression, including one with very low expression. QSP modelling predicted that CD19 expression by immunohistochemistry alone does not predict Lonca response, whereas inclusion of CD19 surface density improved response prediction. Virtual patients responded to Lonca with estimated CD19 as low as 1000 molecules/cell of CD19, normally below the immunohistochemistry detection level. We found Lonca is an effective treatment for R/R DLBCL regardless of CD19 expression by immunohistochemistry. These results provide the basis for future studies addressing CD19-targeted agent sequencing.
Competing Interests: PFC was on the advisory board for ADC Therapeutics SA, Amgen, BeiGene, Bristol Myers Squibb (BMS), Genentech, Kite, MEI Pharmaceuticals and Novartis and received research funding from AbbVie, ADC Therapeutics SA, and Genentech. MH has been a consultant with AbbVie, ADC Therapeutics SA, BMS, Caribou, CRISPR, Gamida Cell, Genmab, Incyte Corporation, Kadmon, Kite, Legend Biotech, MorphoSys, Novartis, Omeros and Seagen; received research funding from ADC Therapeutics SA and Spectrum Pharmaceuticals; has speakers bureau memberships for ADC Therapeutics SA, AstraZeneca, BeiGene, Kite, and Sanofi Genzyme and participated on data monitoring committees for Genentech and Myeloid Therapeutics. CC‐S has been a consultant with Sanofi; has been on the board of directors, speakers bureau or advisory committee for ADC Therapeutics SA, BMS, Celgene, Karyopharm, Roche and Sanofi; has received research funding from ADC Therapeutics SA, Roche and Sanofi and has received honoraria from ADC Therapeutics SA, AstraZeneca, BMS, Incyte, Janssen Oncology, and Takeda. MN is currently employed at Boehringer Ingelheim Pharmaceuticals, Inc. EJ was an employee of Metrum Research Group at the time of the study. KU and TK are currently employed at Metrum Research Group. FZ and YW were employees of ADC Therapeutics SA, a publicaly traded company, at the time of the study and may hold stock. DC, SP and JB are currently employed and current stockholders at ADC Therapeutics SA, a publicly traded company. KH is currently employed and a current stockholder at ADC Therapeutics (UK) Ltd, a publicly traded company. ETHICS STATEMENTThe authors have confirmed an ethical approval statement is not needed for this submission.
(© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)