Rapid T-cell lymphoma progression associated with immune checkpoint inhibitors

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) are widely used for multiple types of malignancies and are considered the fourth pillar in cancer treatment. Anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab are approved for relapsed/refractory classical Hodgkin lymphoma. Nonetheless, two phase 2 trials for T-cell lymphoma were terminated because of hyperprogression after a single dose in some patients.

Areas covered

In this review, we summarize available information on the rapid progression of peripheral T-cell lymphoma including adult T-cell leukemia/lymphoma (ATLL).

Expert opinion

In the abovementioned two trials, disease subtypes in patients who experienced hyperprogression were mostly ATLL or angioimmunoblastic T-cell lymphoma. Possible hyperprogression mechanisms induced by PD-1 blockade are the compensatory upregulation of the expression of other checkpoints, altered expression of lymphoma-promoting growth factors, functional blockade of stromal PD-ligand 1 acting as a tumor suppressor, and unique immune environment in indolent ATLL. The differentiation between hyperprogression and pseudoprogression is practically essential. There are no established methods to predict hyperprogression before administration of an ICI. In the future, the progress of novel diagnostic modalities such as positron emission tomography with computed tomography and circulating tumor DNA is expected to facilitate early cancer detection.

KEYWORDS:

• NTFHL-AI
• ATLL
• hyperprogression
• ICI
• Anti-PD1 antibody

Article highlights

• Immune checkpoint inhibitors (ICIs) are currently approved for many types of malignancies including classical Hodgkin lymphoma

• Clinical investigations of peripheral T-cell lymphoma, including adult T-cell leukemia/lymphoma (ATLL), stagnate partly because hyperprogression occurs shortly after ICI administration.

• The possible hyperprogression mechanisms following anti-programmed death-1 (PD-1) blockade are compensatory upregulation of other checkpoints, altered expression of lymphoma-promoting growth factors, functional blockade of stromal PD-L1, and unique immune environment in indolent ATLL.

• Further mechanical elucidation and standardized clinical management are necessary to prevent hyperprogression, resulting in efficient ICI application.

Acknowledgments

We would like to thank Editage (www.editage.com) for English language editing.

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

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

Additional information

Funding

This paper was not funded.