The impact of omidubicel on immune reconstitution and infections in cord blood transplant patients

ABSTRACT

Introduction

The success of an allogeneic hematopoietic stem cell transplantation (alloHCT) is measured by cure from the underlying malignancy, immune reconstitution (IR), and freedom from graft-versus-host disease, without the continued need for immunosuppressive therapy.

Areas covered

Effective IR is critical to the success of alloHCT wherein poor IR can potentially increase the risk of infection and disease relapse. Different stem cell sources give rise to varying patterns of IR. Particularly with umbilical cord blood transplant, delayed IR is commonly seen with associated increased infection rates and non-relapse mortality, attributable to low CD34+ cell doses and predominance of naïve T cells in the graft. Recent FDA approval of omidubicel, an expanded cord blood graft, was granted due to rapid hematologic recovery and a reduced incidence of high-grade infections associated with improved IR. This review focuses on IR and infections seen with omidubicel and compares those to IR after alloHCT with other graft sources.

Expert opinion

Characteristics of omidubicel, such as ready availability, high infused CD34+ cell dose, and rapid hematologic and immune recovery improve upon the shortcomings of standard umbilical cord blood transplantation. We feel that the data support the emergence of omidubicel as an alternative donor product.

KEYWORDS:

• Omidubicel
• cord blood transplant
• allogeneic hematopoietic stem cell transplant
• immune reconstitution
• infection

Article highlights

• The international, open-label phase 3 trial comparing omidubicel to standard single or double UCBT demonstrated faster time to neutrophil engraftment and reduced incidence of post-transplant high-grade infections with the use of omidubicel.

• Omidubicel utilization provides comprehensive and durable immune reconstitution, most notably with robust CD4+ T-cell recovery within the first 100 days post-UCBT.

• Patients who received omidubicel in the phase 3 trial reported improved health-related quality of life outcomes, likely related to shorter duration of hospital stay, low rates of GVHD and fewer serious infections compared to the unmanipulated UCBT cohort.

• Omidubicel is FDA approved for patients 12 years and older with hematologic malignancies who are planned to receive UCBT after myeloablative conditioning, and is an alternative donor option for patients who lack an available matched donor.

Declaration of interest

RT Maziarz reports serving as consultant for Autolous, Kite/Gilead and Novartis, research support from Gamida, Allovir, OrcaBio, and Novartis, participating in a DSMB for Athersys, Novartis, Century Therapeutics and VorPharma and a patent with Athersys. AP Gandhi reports serving on Orca Bio advisory board. 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.