Allogeneic transplantation and cellular therapies in cutaneous T-cell lymphoma

ABSTRACT

Introduction

Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutaneous T-cell lymphoma. Although many available treatments offer temporary disease control, allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative treatment option for advanced stage MF and SS. CAR T-cell therapy is a promising new avenue for treatment.

Areas covered

In this review, we discuss the evidence supporting the use of allo-HSCT for the treatment of MF/SS, including disease status at the time of transplant, conditioning regimen, total body irradiation (TBI), and donor lymphocyte infusion (DLI). We also address the potential role for CAR T-cell therapy in CTCL.

Expert opinion

Allo-HSCT is an effective treatment for patients with advanced MF and SS. However, significant research is required to determine optimal treatment protocols. Data support the use of reduced-intensity conditioning regimens and suggests that the use of TBI for debulking of skin disease may result in more durable remissions. Donor lymphocyte infusions (DLI) appear to be particularly effective in inducing complete remission in MF/SS patients with relapsed or residual disease. Challenges with CAR-T therapies in T-cell lymphoma include T-cell fratricide due to shared antigens on malignant and nonmalignant T-cells, penetrance into the skin compartment, and CAR-T cell persistence.

KEYWORDS:

• Allogeneic
• CAR-T
• cellular therapy
• cutaneous T-cell lymphoma
• graft-versus-host disease
• hematopoietic stem cell transplant
• mycosis fungoides
• Sezary syndrome

Article highlights

• Allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potentially curative therapy available for patients with advanced mycosis fungoides and Sezary syndrome.

• Patients with SS generally have better outcomes following allo-HSCT than patients with predominant skin involvement as in mycosis fungoides (MF).

• Reduced intensity conditioning (RIC) regimens have similar outcomes and reduced toxicity compared to myeloablative conditioning (MAC) regimens for patients with MF/SS and are preferred in most centers.

• The inclusion of total skin electron beam therapy (TSEBT) as part of the conditioning for debulking of skin disease is widely employed and may improve transplant outcomes, but additional studies are required to compare outcomes with and without TSEBT.

• Donor lymphocyte infusion may induce complete remission in a significant proportion of patients with residual disease or relapse after allo-HSCT.

• The efficacy of RIC over MAC and the response to DLI support the hypothesis that the graft-versus-lymphoma effect is critical to the mechanism of allo-HSCT in treating MF/SS.

• The role of cellular therapy in the treatment of MF/SS is a nascent field and although it holds promise for changing treatment paradigms, significant therapeutic advances are still needed prior to widespread adoption.

Declaration of interest

F Foss has served on the speaker’s bureau for Seagen and Bureau Acrotech, and has served as a consultant for Secura, Kyowa, and Citius.

The authors 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

This paper was not funded.