# JAK Inhibitors in the Treatment of T-Cell Lymphomas: Current Evidence and Future Directions

## TL;DR

This review discusses the potential of JAK inhibitors as a new treatment for T-cell lymphomas, highlighting current evidence and future research needs.

## Contribution

The paper provides a comprehensive overview of JAK inhibitors' current use and future potential in treating T-cell lymphomas.

## Key findings

- Ruxolitinib showed a clinical benefit rate of up to 53% in patients with PTCL and activating JAK/STAT mutations.
- Combination therapies may improve response durations for JAK inhibitors in T-cell lymphomas.
- Safety concerns include cytopenias and infections, with long-term data still lacking for newer agents.

## Abstract

T-cell lymphomas are cancers that originate from white blood cells called T-cell lymphocytes. These cancers can grow slowly or aggressively, and they can affect any part of the body, including the skin and lymph nodes. New treatments are needed for patients with T-cell lymphomas that have become resistant to treatment. Drugs called Janus kinase (JAK) inhibitors may be an effective treatment option for these patients. The first commercially available JAK inhibitor, ruxolitinib, was found to be safe and effective in early-phase clinical trials. Additional JAK inhibitors are currently in clinical development for patients with T-cell lymphomas. Future studies will be needed to determine how well these drugs work in larger groups of patients and to clarify any long-term adverse effects. The purpose of this review is to provide an overview of these medications in the treatment of T-cell lymphomas.

T-cell lymphomas are a heterogeneous group of lymphoid neoplasms with a variable prognosis. They can be further divided into cutaneous T-cell lymphomas and peripheral T-cell lymphomas. Treatment options are relatively limited for patients with relapsed or refractory disease. Janus kinase (JAK) inhibitors have emerged as promising new drugs for these lymphomas, as increasing evidence supports the JAK and signal transducer and activator of transcription (STAT) pathway as a potential target. The objective of this review is to summarize the current evidence supporting the use of JAK inhibitors in the treatment of T-cell lymphomas and highlight areas for future research. Although many JAK inhibitors have been developed for the treatment of autoimmune conditions, only a subset of these have been tested in T-cell lymphomas and reported in the literature. These include abrocitinib, cerdulatinib, golidocitinib, ruxolitinib, tofacitinib, and upadacitinib. Other drugs are currently being tested in clinicals trials, including pacritinib and ivarmacitinib, but results are not yet available. Most of the published data are for ruxolitinib, which was found to have a clinical benefit rate of up to 53% in patients with PTCL with activating JAK and/or STAT mutations. Response durations are limited, which may be overcome through combination therapies in the future. JAK inhibitors are associated with multiple adverse effects, including cytopenias and infections, and long-term safety data are lacking for newer agents. Future studies will need to clarify long-term safety and efficacy through well-designed clinical trials involving larger groups of patients.