Anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory B-cell malignancies: a narrative review with focus on diffuse large B-cell lymphoma.

Abstract

PURPOSE:

CD19 is a cell surface protein that is found on both healthy and malignant B cells. Accordingly, it has become an important target for novel treatments for non-Hodgkin lymphomas and B-cell leukaemia. Three anti-CD19 monoclonal antibodies with distinct mechanisms of action have been developed for the treatment of B-cell malignancies.

METHODS:

We reviewed the preclinical and clinical data on the development of the newly approved anti-CD19 monoclonal antibodies blinatumomab, tafasitamab and loncastuximab tesirine, and consider their place in the treatment of relapsed or refractory B-cell malignancies.

RESULTS:

Blinatumomab is a bispecific T-cell engager that binds to both CD19 on B cells and CD3 on T cells, facilitating antibody-dependent cytotoxicity. Blinatumomab significantly prolongs overall survival in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, although cytokine release syndrome and severe neurotoxicity may necessitate discontinuation. Tafasitamab, which has modified anti-CD19 Fab and Fc regions, has significantly enhanced affinity for both CD19 and effector cell receptors compared with unmodified anti-CD19. In L-MIND, tafasitamab plus lenalidomide provided an overall response rate (ORR) of 57.5% in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients non-transplant eligible. Loncastuximab tesirine is an antibody-drug conjugate that has been studied as monotherapy and in combination with ibrutinib in 3L + relapsed or refractory DLBCL. The ORR was 48.3% in a phase II trial of loncastuximab tesirine. The optimal place of anti-CD19 monoclonal antibodies in therapy has yet to be determined, but the prospect of improved outcomes for at least some patients with treatment-resistant B-cell malignancies appears likely, particularly in those with limited therapeutic options and poor prognosis.

• Authors: Pier Luigi Zinzani, Giorgio Minotti
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 148 Issue 1 Pg. 177-190 (Jan 2022) ISSN: 1432-1335 [Electronic] Germany
• PMID: 34741682 (Publication Type: Journal Article, Review)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibodies, Bispecific
• Antibodies, Monoclonal, Humanized
• Antigens, CD19
• Antineoplastic Agents
• CD19 molecule, human
• Immunoglobulin Fab Fragments
• Immunoglobulin Fc Fragments
• Piperidines
• Benzodiazepines
• ibrutinib
• blinatumomab
• loncastuximab tesirine
• Adenine
• tafasitamab

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Antibodies, Bispecific (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antigens, CD19 (immunology)
• Antineoplastic Agents (therapeutic use)
• B-Lymphocytes (immunology, metabolism)
• Benzodiazepines (therapeutic use)
• Drug Evaluation, Preclinical
• Humans
• Immunoglobulin Fab Fragments (immunology)
• Immunoglobulin Fc Fragments (immunology)
• Lymphoma, Large B-Cell, Diffuse (drug therapy)
• Piperidines (therapeutic use)