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Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a profile of its use in the USA

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Abstract

The antibody-drug conjugate (ADC) loncastuximab tesirine (loncastuximab tesirine-lpyl, Zynlonta®), is a useful option for third-line and subsequent treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Loncastuximab tesirine comprises a humanized anti-CD19 antibody linked to a pyrrolobenzodiazepine (PBD) dimer cytotoxic alkylating agent. It is the first CD19-targeted ADC approved for third-line and subsequent treatment of relapsed or refractory large B-cell lymphoma, DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. In the pivotal phase II LOTIS-2 trial, loncastuximab tesirine as monotherapy produced an overall response rate (ORR) of 48% in heavily pre-treated patients with relapsed or refractory DLBCL, some of whom had previously received chimeric antigen receptor (CAR)-T cell therapy or hematopoietic stem cell transplantation (HSCT). The adverse event profile of loncastuximab was consistent with that seen with other PBD-based treatments, characterized by fluid overload and elevated γ-glutamyl transferase levels.

Plain Language Summary

Loncastuximab tesirine (Zynlonta®) is a novel anticancer therapy that uses a humanized antibody to deliver a toxic drug payload directly to cancer cells. The antibody component of loncastuximab tesirine targets a cell surface protein called CD19 that is unique to B lymphocytes, a type of white blood cell. Upon binding to CD19 on the cell surface, the antibody-drug conjugate is drawn inside, whereupon the toxic payload is released. Loncastuximab tesirine is approved in the USA for third-line and subsequent treatment of adult patients with relapsed or refractory large B-cell lymphoma including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. In the pivotal clinical trial that led to this approval, loncastuximab tesirine monotherapy produced an overall response rate of 48% in heavily pre-treated patients with relapsed or refractory DLBCL, and had an adverse event profile consistent with that seen with other treatments that use the same toxic payload. On this basis, monotherapy with loncastuximab tesirine can be considered as a useful option for third-line and subsequent treatment of DLBCL.

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Acknowledgements

The manuscript was reviewed by: J.P. Alderuccio, Division of Hematology, Sylvester Comprehensive Cancer Center, Miami, FL, USA; F. Rustemi, Health Insurance Fund, Tirana, Albania. During the peer review process, ADC Therapeutics SA, the marketing authorization holder of loncastuximab tesirine, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Anthony Markham & Zaina T. Al-Salama

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  1. Anthony Markham
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  2. Zaina T. Al-Salama
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Correspondence to Zaina T. Al-Salama.

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A. Markham is a salaried employee of Adis International Ltd/Springer Nature and declares no relevant conflicts of interest. Z.T. Al-Salama, a salaried employee of Adis International Ltd/Springer Nature and an editor of Drugs & Therapy Perspectives, was not involved in any publishing decisions for the manuscript and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Markham, A., Al-Salama, Z.T. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a profile of its use in the USA. Drugs Ther Perspect 38, 261–267 (2022). https://doi.org/10.1007/s40267-022-00922-w

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