Improved Therapeutic Approaches are Needed to Manage Graft-versus-Host Disease

Abstract

Allogeneic haematopoietic stem cell transplantation (alloHSCT) offers a potentially curative therapy for patients suffering from diseases of the haematopoietic system but requires a high level of expertise and is both resource intensive and expensive. A frequent and life-threatening complication is graft-versus-host disease (GvHD). Acute GvHD (aGvHD) generally causes skin, gastrointestinal and liver symptoms, but chronic GvHD (cGvHD) has a different pathophysiology and may affect nearly every organ or tissue of the body. In Europe, GvHD prophylaxis is generally a calcineurin inhibitor in combination with methotrexate, with high-dose systemic steroids used for advanced GvHD treatment. Between 39% and 59% of alloHSCT patients will develop aGvHD and around 36-37% will develop cGvHD. Steroid response decreases with increasing disease severity, which in turn leads to an increase in non-relapse mortality. GvHD imposes a financial burden on healthcare systems, significantly increasing post-alloHSCT costs. Increased GvHD disease severity magnifies this. Balancing immunosuppression to control the GvHD whilst maintaining a degree of immunocompetence against infection is critical. European GvHD guidelines acknowledge the lack of evidence to support a standard second-line therapy, and improved long-term outcomes and quality-of-life (QoL) remain an unmet need. Evidence generation for potential treatments is challenging. Issues to overcome include choice of comparator (extensive off-label usage); blinding; selection of relevant patient-reported outcome measures (PROMs); and rarity of the condition, which may infeasibly increase timescales to achieve clinical and statistical relevance.

A cost-effectiveness analysis of ruxolitinib versus best alternative therapy for patients with steroid-refractory chronic graft-versus-host disease aged > 12 years in Singapore

“…To ensure the success of this procedure and maximize value gained, it is critical for patients to be able to access the most effective post-transplant supportive care. Despite significant progress in recent years, there remains an unmet need to improve long-term posttransplant outcomes of allo-HSCT recipients [ 20 ]. A key determinant of the long-term QoL of patients who undergo HSCT is the occurrence and severity of GVHD [ 20 ].…”

“…Despite significant progress in recent years, there remains an unmet need to improve long-term posttransplant outcomes of allo-HSCT recipients [ 20 ]. A key determinant of the long-term QoL of patients who undergo HSCT is the occurrence and severity of GVHD [ 20 ]. Patients with SR-cGVHD after allo-HSCT are significantly impacted, with the mean total cost after 2 years of the transplant increasing to more than double (United States dollar [USD] 532,673) compared with those without cGVHD (USD 252,909; P < 0.001) [ 21 ].…”

Clinical and economic burden associated with graft-versus-host disease following allogeneic hematopoietic cell transplantation in France

“…An unmet need exists for effective therapies to prevent and treat GVHD following allo-HSCT [ 12 ]. Treatment options for GVHD are largely limited to systemic corticosteroids and, specifically for patients with cGVHD, immunosuppressants [ 13 ].…”

Clinical and Economic Burden Associated with Graft-Versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation in France

“…(8) An unmet need exists for effective therapies to prevent and treat GVHD following allo-HSCT. (9) Treatment options for GVHD are largely limited to systemic corticosteroids and, speci cally for patients with cGVHD, immunosuppressants. (10) Currently, there is no standard second-line treatment for patients who become resistant to or dependent on corticosteroids.…”