Cyclosporine for angioimmunoblastic T-cell lymphoma: a literature review

ABSTRACT

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a type of peripheral T-cell lymphomas harboring aggressive biological behaviors and presenting unique immunologic hyperactivation. Gene expression profiling has revealed that AITL cells derive from follicular T helper (Tfh) cells. The prognosis is poor under CHOP-like regimen, and salvage chemotherapy is mostly ineffective. Thus, novel therapies are required in patients with AITL. NCCN Guidelines for peripheral T-cell lymphoma refer to cyclosporin (CyA) as one therapeutic option in second- or later lines especially for AITL cases unfeasible for hematopoietic stem-cell transplantation (HSCT). The clinical data of AITL are based on small-scale case series, and prospective trials are scarce.

Areas covered: In this article, the authors reviewed published articles or conference abstracts, and extracted total 26 patients with AITL receiving CyA.

Expert opinion: The overall response rate in above 26 patients was outstanding (86% in second or later lines), suggesting the utility in heavily treated cases including those who underwent HSCT. Meanwhile, publication bias is the most serious limitation in this literature review. Larger case series or prospective data with CyA alone or in combination with other drugs are warranted to establish the position in the treatment strategy of patients with AITL.

KEYWORDS:

• Angioimmunoblastic T-cell lymphoma
• follicular T helper cells
• cyclosporin
• novel agents
• salvage chemotherapy

Article highlights

• Gene expression profiles in AITL have indicated that the origin of AITL cells derives from follicular T helper (Tfh) cells.

• Patients with AITL often experience clinical relapse after temporary response, and novel therapies to improve the prognosis are strongly warranted.

• Cyclosporin (CyA) inhibits T-cell activation by binding to cyclophilin in T-cells and suppresses differentiation of Tfh cells from naïve CD4⁺ T-cells.

• Regardless of small sample size, the overall response rate of CyA (>80%) was promising even in second or later lines, and prospective clinical trials with CyA or combinational chemotherapies incorporating CyA in patients with AITL are warranted.

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.