The AntiCD19 Antibody Drug Immunoconjugate Loncastuximab Achieves Responses in DLBCL Relapsing After AntiCD19 CAR-T Cell Therapy

Paolo F Caimi; Kirit M Ardeshna; Erin Reid; Weiyun Ai; Matthew Lunning; Jasmine Zain; Melhem Solh; Brad S Kahl; Mehdi Hamadani

doi:10.1016/j.clml.2021.11.005

The AntiCD19 Antibody Drug Immunoconjugate Loncastuximab Achieves Responses in DLBCL Relapsing After AntiCD19 CAR-T Cell Therapy

Clin Lymphoma Myeloma Leuk. 2022 May;22(5):e335-e339. doi: 10.1016/j.clml.2021.11.005. Epub 2021 Nov 12.

Authors

Paolo F Caimi¹, Kirit M Ardeshna², Erin Reid³, Weiyun Ai⁴, Matthew Lunning⁵, Jasmine Zain⁶, Melhem Solh⁷, Brad S Kahl⁸, Mehdi Hamadani⁹

Affiliations

¹ Cleveland Clinic/Case Comprehensive Cancer Center, Cleveland, OH. Electronic address: [email protected].
² Department of Hematology, University College London Hospitals (UCLH) NHS Foundation Trust, London, UK.
³ Division of Hematology and Oncology, Department of Medicine, University of California, San Diego, CA.
⁴ Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA.
⁵ Division of Oncology and Hematology, Department of Medicine, University of Nebraska Medical Center, Omaha, NE.
⁶ Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA.
⁷ Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA.
⁸ Department of Medicine, Oncology Division, Washington University, St. Louis, MO.
⁹ BMT & Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI.

PMID: 35034868
DOI: 10.1016/j.clml.2021.11.005

Abstract

Introduction: Chimeric antigen receptor T (CAR-T) cells targeting CD19 result in durable responses in approximately 40% of DLBCL patients. Loncastuximab tesirine, an antibody drug conjugate targeting CD19 with a pyrrolobenzodiazepine payload, has activity against DLBCL.

Patients and methods: We evaluated the outcomes of 13 DLBCL patients relapsed after CAR-T cells treated with loncastuximab in the LOTIS-2 trial.

Results: Six patients (46%) had responses to loncastuximab (CR, n = 2). Median OS, PFS and duration of response after loncastuximab were 8.2, 1.4 and 8 months, respectively.

Conclusion: Loncastuximab can achieve responses in patients progressing after CAR-T cells. Sequencing CD19-targeting therapies is possible in cases without CD19 loss.

Keywords: CAR-T cell failures; Diffuse large B cell lymphoma.

MeSH terms

Antigens, CD19
Antineoplastic Agents* / therapeutic use
Cell- and Tissue-Based Therapy
Humans
Immunoconjugates* / pharmacology
Immunoconjugates* / therapeutic use
Immunotherapy, Adoptive
Receptors, Chimeric Antigen*

Substances

Antigens, CD19
Antineoplastic Agents
Immunoconjugates
Receptors, Chimeric Antigen