Abatacept as salvage therapy in chronic graft-versus-host disease—a retrospective analysis

Wertheimer, Tobias; Dohse, Marius; Afram, Gabriel; Weber, Daniela; Heidenreich, Martin; Holler, Barbara; Kattner, Anna-Sophia; Neubauer, Andreas; Mielke, Stephan; Ljungman, Per; Holler, Ernst; Herr, Wolfgang; Edinger, Matthias; Martínez, A. Pérez; Fante, Matthias; Wolff, Daniel

doi:10.1007/s00277-021-04434-x

Cited by 12 publications

(8 citation statements)

References 43 publications

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“…Axatilimab, a humanized antibody against macrophage colony-stimulating factor receptor (CSF-1R), is in an active phase II clinical trial to dampen pulmonary fibrosis in cGVHD [ 12 ]. Abatacept (Orencia) is an immunomodulatory fusion protein currently being investigated for its efficacy in treating steroid-refractory cGVHD [ 13 ]. Abatacept recently became the first drug FDA approved specifically for aGVHD prophylaxis in December 2021 but is contraindicated in the presence of a JAK inhibitor, such as ruxolitinib.…”

Section: Discussionmentioning

confidence: 99%

Concomitant Ruxolitinib and Ibrutinib for Graft-Versus-Host Disease (GVHD): The First Reported Use in Pediatric Patients

Gagliardi¹,

Milner²,

Cairo³

et al. 2022

Cureus

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Allogeneic hematopoietic stem cell transplant (alloHSCT) can be a life-saving treatment for patients with hematological disorders but far too often carries the feared complication of graft-versus-host disease (GVHD). The first-line treatment of GVHD is typically corticosteroids, but steroid-refractory chronic GVHD (cGVHD) has led to the Food and Drug Administration (FDA) approval of ruxolitinib (Jakafi), ibrutinib (Imbruvica), and belumosudil (Rezurock).Patient 1 was a four-year-old female diagnosed with natural killer (NK) cell dysfunction who underwent alloHSCT with cells from a 9/10 National Marrow Donor Program (NMDP) donor and subsequently developed chronic GVHD (cGVHD) of the skin and gut. This cGVHD was refractory to steroids and ibrutinib but improved with the administration of concomitant ibrutinib and ruxolitinib. Patient 2 was a one-year-old male with sickle cell anemia. The patient was transplanted under a haploidentical protocol from the mother but developed bronchiolitis obliterans organizing pneumonia (BOOP) and pathology-confirmed GVHD. This cGVHD was steroid-refractory and resolved with the administration of concomitant ibrutinib and ruxolitinib. To our knowledge, this is the first reported use of concomitant ruxolitinib and ibrutinib in pediatric patients. The combination was well tolerated with no significant adverse events. Neither patient had to discontinue these drugs. We propose a further investigation into this dual therapy in cGVHD either compared to steroids or as a second-line option.

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Section: Discussionmentioning

confidence: 99%

Concomitant Ruxolitinib and Ibrutinib for Graft-Versus-Host Disease (GVHD): The First Reported Use in Pediatric Patients

Gagliardi¹,

Milner²,

Cairo³

et al. 2022

Cureus

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“…Abatacept was noted to have significant, durable clinical improvement as measured by an 89% improvement based on lung severity score or lung function measured by pulmonary function test. 39 …”

Section: Using Abatacept To Treat and Prevent Chronic Gvhdmentioning

confidence: 99%

Role of abatacept in the prevention of graft-versus-host disease: current perspectives

Ngwube

Rangarajan

Shah

2023

Therapeutic Advances in Hematology

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Administration of abatacept following transplantation has been reported to inhibit graft rejection and graft- versus-host-disease (GvHD) in mouse models associated with allogeneic hematopoietic stem cell transplant (HSCT). This strategy has recently been adopted in clinical practice for GvHD prevention in human allogeneic HSCT and offers a unique approach to optimizing GvHD prophylaxis following alternative donor HSCTs. When combined with calcineurin inhibitors and methotrexate, abatacept had shown to be safe and effective in preventing moderate to severe acute GvHD in myeloablative HSCT using human leukocyte antigen (HLA) unrelated donors. Equivalent results are being reported in recent studies using alternative donors, in reduced-intensity conditioning HSCT and nonmalignant disorders. These observations have led to hypothesizing that even in the setting of increasing donor HLA disparity, abatacept when given with traditional GvHD prophylaxis does not worsen general outcomes. In addition, in limited studies, abatacept have being protective against the development of chronic GvHD through extended dosing and in the treatment of steroid-refractory chronic GvHD. This review summarized all the limited reports of this novels approach in the HSCT setting.

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“…Abatacept, a costimulatory signal blocker which inhibits T cell activation, has been also evaluated in small cohorts of adult patients with SR-cGvHD and showed 40-44% ORR. As for pomalidomide, paediatric data are missing (203,209).…”

Section: New and Emerging Therapiesmentioning

confidence: 99%

Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan

Sobkowiak-Sobierajska

Lindemans

Sýkora

et al. 2022

Front. Pediatr.

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Herein we review current practice regarding the management of chronic graft-vs.-host disease (cGvHD) in paediatric patients after allogeneic haematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukaemia (ALL). Topics covered include: (i) the epidemiology of cGvHD; (ii) an overview of advances in our understanding cGvHD pathogenesis; (iii) current knowledge regarding risk factors for cGvHD and prevention strategies complemented by biomarkers; (iii) the paediatric aspects of the 2014 National Institutes for Health-defined diagnosis and grading of cGvHD; and (iv) current options for cGvHD treatment. We cover topical therapy and newly approved tyrosine kinase inhibitors, emphasising the use of immunomodulatory approaches in the context of the delicate counterbalance between immunosuppression and immune reconstitution as well as risks of relapse and infectious complications. We examine real-world approaches of response assessment and tapering schedules of treatment. Furthermore, we report on the optimal timepoints for therapeutic interventions and changes in relation to immune reconstitution and risk of relapse/infection. Additionally, we review the different options for anti-infectious prophylaxis. Finally, we put forth a theory of a holistic view of paediatric cGvHD and its associated manifestations and propose a checklist for individualised risk evaluation with aggregated considerations including site-specific cGvHD evaluation with attention to each individual's GvHD history, previous medical history, comorbidities, and personal tolerance and psychosocial circumstances. To complement this checklist, we present a treatment algorithm using representative patients to inform the personalised management plans for patients with cGvHD after HSCT for ALL who are at high risk of relapse.

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Abatacept as salvage therapy in chronic graft-versus-host disease—a retrospective analysis

Cited by 12 publications

References 43 publications

Concomitant Ruxolitinib and Ibrutinib for Graft-Versus-Host Disease (GVHD): The First Reported Use in Pediatric Patients

Concomitant Ruxolitinib and Ibrutinib for Graft-Versus-Host Disease (GVHD): The First Reported Use in Pediatric Patients

Role of abatacept in the prevention of graft-versus-host disease: current perspectives

Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan

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