Pralatrexate injection for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma

ABSTRACT

Introduction

Peripheral T cell lymphomas (PTCL) are a heterogenous group of lymphoproliferative disorders which are generally not curable with conventional chemotherapy and associated with inferior outcomes. Pralatrexate is a novel folate analog, the first FDA approved drug) for the treatment of relapsed/refractory (R/R) PTCL.

Areas covered

This paper provides a comprehensive review of PubMed literature describing the use of pralatrexate in R/R peripheral T-cell lymphoma. Pharmacokinetics and mechanism of action of pralatrexate are discussed as well as its clinical efficacy and safety in comparison to other agents available in R/R PTCL.

Expert opinion

Pralatrexate is an active agent in relapsed/refractory PTCL with lower response rates seen in patients with angioimmunoblastic T cell lymphomas. Mucositis is the most frequently observed adverse event and this can be mitigated by the use of leucovorin along with cyanocobalamin and folic acid.

KEYWORDS:

• Pralatrexate
• relapsed or refractory
• peripheral T-cell lymphoma
• folate antagonist
• PROPEL

Article Highlights

• Pralatrexate is a novel folate antagonist which binds to the reduced folate carrier

• Pralatrexate is active in aggressive subsets of peripheral T cell lymphoma with an overall response rate of 29% in the PROPEL study. Responses were seen in heavily pretreated patients.

• Single agent pralatrexate has been a successful bridge to potentially curative allogeneic transplant in a subset of patients treated on the PROPEL study

• Toxicities of pralatrexate include mucosal inflammation which can be ameliorated by administration of leucovorin 24 hours after pralatrexate treatment.

• Dermatologic toxicities and skin flare have been seen with pralatrexate, especially in patients with cutaneous T cell lymphomas and have been successfully managed with topical and systemic steroids and dose reductions

• Combination therapies with pralatrexate and romidepsin, bortezomib, and other agents have been explored in clinical trials.

Box 1. Drug summary

Table

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.