Novel antibodies which have an impact on immune status after allogeneic hematopoietic cell transplantation

ABSTRACT

Introduction

In the field of hematological malignancy, we often have the opportunity to use antibodies such as immune checkpoint inhibitors that can alter a patient’s immune status before or after allo-HCT. The appropriate use of these novel agents is highly necessary to optimize disease control and reduce the risk of complications associated with adverse allo-immune reactions.

Areas covered

Clinical data on several monoclonal antibodies targeting programmed cell death 1 (PD-1) (nivolumab or pembrolizumab), C-C chemokine receptor 4 (CCR4) (mogamulizumab), CD30 (brentuximab vedotin), or cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) (ipilimumab) are reviewed, with a focus on the incidence and severity of graft-versus-host disease (GVHD).

Expert opinion

While previous studies demonstrated a favorable prognosis in patients who received nivolumab prior to transplantation, the pretransplant use of nivolumab increases the incidence of GVHD, partly due to the expansion and activation of preexisting T cells. Mogamulizumab also has a significant impact on GVHD, caused by persistent depletion of regulatory T cells with CCR4 positivity. Regarding brentuximab vedotin, phase 1 trials have demonstrated considerable efficacy for steroid-refractory acute or chronic GVHD. In the future, sophisticated methods will be needed to determine the impact of each agent on immune status after allo-HCT.

KEYWORDS:

• Allo-HCT
• GVHD
• nivolumab
• pembrolizumab
• mogamulizumab
• brentuximab vedotin
• ipilimumab

Article highlights

• Recently, various drugs targeting surface molecules on immune cells have been developed for the treatment of hematological malignancies. These drugs could have a significant impact on the immune status of patients who undergo allo-HCT.

• Pretransplant administration of anti-PD-1 antibodies may increase the incidence of GVHD, and one promising approach to counteract this is post-transplant cyclophosphamide treatment.

• A previous study showed that a short interval (< 50 days) between mogamulizumab administration and allo-HCT was associated with an increased risk of both severe acute GVHD and non-relapse mortality.

• Phase 1 trials of brentuximab vedotin have demonstrated considerable efficacy against steroid-refractory acute or chronic GVHD.

• In the future, sophisticated methods are warranted to clarify the impact of each novel drug on immune status after allo-HCT.

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 study was partly supported by Health, Labor, and Welfare Sciences Research Grants (20FF1002).