CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell lymphomas

ABSTRACT

Introduction: Ubiquitous expression of CD19 on B cell non-Hodgkin lymphoma identified it as a potential target for immune-based therapies.

Areas covered: This article reviews the current literature on anti-CD19 therapies currently in clinical trials including monoclonal antibodies (mAb), antibody targeted cytotoxic drug conjugates (ADC), bispecific antibodies, and chimeric antigen receptor (CAR) modified T cells.

Expert opinion: Naked anti-CD19 mAbs have shown little clinical benefit in B cell lymphomas. Despite unusual toxicity profiles with many anti-CD19 ADCs slowing development, durable remissions in a substantial minority of patients with refractory aggressive lymphomas should encourage continued efforts in this area. Blinatumomab, an anti-CD19 bispecific T cell engager, has shown impressive responses in relapse/refractory diffuse large B cell lymphoma (DLBCL), but is plagued by neurotoxicity issues and the need for continuous infusion. CD19 targeting CAR-T cell therapies are the most promising, with the potential for curing a third of refractory DLBCL patients. There is still much work to be done to address potentially life-threatening cytokine release syndrome and neurotoxicity, an extended production time precluding patients with rapidly progressive disease, and treatment expense. However, if the promise of CAR-T cell technology is confirmed, this will likely change the approach and prognosis for relapse/refractory aggressive lymphoma.

KEYWORDS:

• CD19
• B cell lymphoma
• CAR-T cells
• blinatumomab
• antibody drug conjugates

Article highlights

• CD19, a B cell specific member of the immunoglobulin family and highly expressed in nearly all B cell malignancies, making it an attractive receptor for novel targeted therapies for B cell lymphoma.

• Current naked anti-CD19 monoclonal antibodies have modest activity in B cell lymphomas as single agents. Combination studies of MEDI-551 with chemotherapy have shown no benefit over existing CD20 monoclonal antibody combinations, although additional combination studies with other anti-CD19 mAbs are pending.

• Bispecific antibodies directed against CD19 and CD3, as well as anti-CD19 antibody drug conjugates have shown encouraging results in early clinical trials, however unique toxicity profiles still need to be addressed.

• Chimeric antigen receptor (CAR)-T cell therapy directed against CD19 was recently FDA-approved for treatment of refractory diffuse large B cell lymphoma based on high response rates and the potential for durable remissions in approximately one third of patients.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee has declared having served advisory board member with Amgen and Gilead/Kite.

Additional information

Funding

This paper was not funded.