New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature

ABSTRACT

Introduction

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a formidable obstacle in the field of allogeneic hematopoietic cell transplantation (allo-HCT), significantly contributing to patient morbidity and mortality. The current therapeutic landscape for SR-aGVHD is limited, often yielding suboptimal results, thereby emphasizing the urgent need for innovative and effective treatments.

Areas Covered

In light of the pivotal REACH2 trial, ruxolitinib phosphate, a Janus kinase inhibitor, has gained prominence as the standard treatment for SR-aGVHD. Nevertheless, a considerable number of patients either do not respond to or cannot tolerate this therapy. This review delves into emerging treatments for SR-aGVHD, including mesenchymal stromal cells (MSCs), fecal microbiota transplantation (FMT), CD3/CD7 blockade, neihulizumab, begelomab, tocilizumab, and vedolizumab. While some of these agents have shown encouraging results in early-phase trials, issues such as treatment-related toxicities and inconsistent responses in larger studies highlight the necessity for ongoing research.

Expert Opinion

Current trials exploring new agents and combination therapies offer hope for fulfilling the unmet clinical needs in SR-aGVHD, potentially leading to more effective and precise treatment strategies.

KEYWORDS:

• GvHD
• steroid refractory
• ruxolitinib
• mesenchymal stem cells
• tocilizumab

Article highlights

• Steroid refractory (SR)-aGVHD remains a formidable complication post-HCT and the development of innovative therapeutic approaches remains a clinical priority.

• Ruxolitinib phosphate was granted approval by the US FDA for treating SR-aGVHD in 2019 and represents a major advance.

• Biomarkers (ST2 and REG3α) can predict outcomes of steroid-resistant GVHD patients, and in the future may help develop risk adapted novel approaches for management of this complication.

Declaration of interest

M Hamadani reports Research support/Funding: ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma; Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, AbbVie, Caribou, Genmab, CRISPR, Autolus. Speaker’s Bureau: ADC Therapeutics, AstraZeneca, BeiGene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, S Abedin reports Research Funding: Actinium Pharmaceuticals, Incyte Inc, Altrubio Inc; Consulting: AbbVie, Servier Pharmaceuticals, Daiichi Sankyo

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.