Immune-based therapies in diffuse large B-cell lymphoma

ABSTRACT

Introduction

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and clinically heterogeneous malignancy originating from B-cells with up to 40% of patients experiencing primary refractory disease or relapse after first-line treatment. However, the past 5 years have seen a flurry of new drug approvals for DLBCL anchored upon new immune therapies, including chimeric antigen receptor (CAR) T-cells and antibody-based therapies.

Areas covered

This article summarizes recent advances in the treatment of DLBCL, including in the first line and relapsed and refractory setting (second-line and beyond). A literature search was conducted for publications relevant to the immunotherapeutic approach to DLBCL from 2000 through March 2023 within PubMed and articles were reviewed. The search terms were immunotherapy, monoclonal antibodies, chimeric antigen receptor modified T-cell (CAR-T), and classification of DLBCL. Relevant clinical trials and pre-clinical studies exploring the strengths and weaknesses of current immune therapies against DLBCL were chosen. We additionally explored how intrinsic differences amongst DLBCL subtype biology and endogenous host immune recruitment contribute to variable therapeutic efficacy.

Expert Opinion

Future treatments will minimize chemotherapy exposure and be chosen by underlying tumor biology, paving the way for the promise of chemotherapeutic free regimens and improved outcomes for poor-risk subgroups.

KEYWORDS:

• Antibody therapies
• CAR T-cells
• Diffuse large B-Cell lymphoma
• Immunotherapies
• Endogenous anti-tumor immune response

Article highlights

• Immunotherapeutic approaches in DLBCL have transformed the field in the past 5 years

• Chimeric antigen receptor (CAR) T cell-based therapy has demonstrated improved outcomes in the relapsed or refractory (R/R) disease setting and is now being studied in the first-line

• Approvals of antibody-drug conjugates, such as polatuzumab monomethyl auristatin E and loncastuximab tesirine in the R/R disease setting have occurred.

• When added to first line chemoimmunotherapy, polatuzumab monomethyl auristatin E improved progression-free survival and is now approved by the FDA in the United States and approved in other countries.

• Chemotherapy-free or sequenced regimens to enable and increase host immune effector cell functions display promise in phase 1 & 2 clinical trials.

• New insight into DLBCL biology provide the potential to generate more therapies to address unmet needs for DLBCL patients

Declaration of interest

C Flowers:

• Consultant: Abbvie, Bayer, BeiGene, Celgene, Denovo Biopharma, Foresight Diagnostics, Genentech/Roche, Genmab, Gilead, Karyopharm, N-Power Medicine, Pharmacyclics/Janssen, SeaGen, Spectrum.

• Stock/Stock Options: Foresight Diagnostics, N-Power Medicine

• Research Funding:

• 4D, Abbvie, Acerta, Adaptimmune, Allogene, Amgen, Bayer, Celgene, Cellectis EMD, Gilead, Genentech/Roche, Guardant, Iovance, Janssen Pharmaceutical, Kite, Morphosys, Nektar, Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda, TG Therapeutics, Xencor, Ziopharm, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, National Cancer Institute, Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research

D McCurry and C Bermack have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Dr. Flowers receives research funding from the Cancer Prevention and Research Institute of Texas and is a CPRIT Scholar in Cancer Research