Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

Madon, E; Giaccone, Luisa; Festuccia, Moreno; Brunello, Lucia; Buondonno, Ilaria; Ferrero, Dario; Boccadoro, Mario; Dellacasa, Chiara Maria; Busca, Alessandro; Novero, Domenico; Bruno, Benedetto

doi:10.1186/s13045-016-0298-6

Cited by 20 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One patient with cGVHD died from a GVHD flare following ruxolitinib discontinuation; the remaining patients were successfully treated with a low maintenance dose of ruxolitinib or slow tapering following response to treatment. Similar findings have been reported in adult patients with aGVHD or cGVHD [35,[42][43][44] and pediatric patients with aGVHD [45]. These data suggest that ruxolitinib provides clinical benefit and durable responses in patients with SR GVHD; however, further data from large prospective clinical trials are required.…”

Section: Overview Of Ruxolitinib and Rationale For Targeting Jak Signalsupporting

confidence: 80%

Ruxolitinib for the Treatment of Patients with Steroid-Refractory GVHD: An Introduction to the REACH Trials

et al. 2018

View full text Add to dashboard Cite

For patients with hematologic malignancies and disorders, allogeneic hematopoietic stem cell transplantation offers a potentially curative treatment option. Many patients develop graft-versus-host disease (GVHD), a serious complication and leading cause of nonrelapse mortality. Corticosteroids are the standard first-line treatment for GVHD; however, patients often become steroid-refractory or remain corticosteroiddependent. New second-line treatment options are needed to improve patient outcomes. Here we review the role of JAK1 and JAK2 in acute and chronic GVHD. We also describe the study designs of the Phase II REACH1 (NCT02953678) and the Phase III REACH2 (NCT02913261) and REACH3 (NCT03112603) clinical trials that are currently recruiting patients to evaluate the JAK1/JAK2 inhibitor ruxolitinib in patients with corticosteroid-refractory acute or chronic GVHD.

show abstract

Section: Overview Of Ruxolitinib and Rationale For Targeting Jak Signalsupporting

confidence: 80%

Ruxolitinib for the Treatment of Patients with Steroid-Refractory GVHD: An Introduction to the REACH Trials

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The patient ultimately developed cGVHD 2 months after tapering and discontinuing ruxolitinib. Finally, in a case study, ruxolitinib was associated with complete resolution of grade 2 aGVHD in the gastrointestinal tract and skin after 21 days of treatment, as confirmed by histology (71).…”

Section: Clinical Evidence With Jak1/jak2 Inhibitorsmentioning

confidence: 86%

The Role of Janus Kinase Signaling in Graft-Versus-Host Disease and Graft Versus Leukemia

Schroeder

Choi

Staser

et al. 2018

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

For patients with hematologic malignancies, allogeneic hematopoietic cell transplantation (alloHCT) offers a potential curative treatment option, primarily due to an allogeneic immune response against recipient tumor cells (ie, graft-versus-leukemia [GVL] activity). However, many recipients of alloHCT develop graft-versus-host disease (GVHD), in which allogeneic immune responses lead to the damage of healthy tissue. GVHD is a leading cause of nonrelapse mortality and a key contributor to morbidity among patients undergoing alloHCT. Therefore, improving alloHCT outcomes will require treatment strategies that prevent or mitigate GVHD without disrupting GVL activity. Janus kinases (JAKs) are intracellular signaling molecules that are well positioned to regulate GVHD. A variety of cytokines that signal through the JAK signaling pathways play a role in regulating the development, proliferation, and activation of several immune cell types important for GVHD pathogenesis, including dendritic cells, macrophages, T cells, B cells, and neutrophils. Importantly, despite JAK regulation of GVHD, preclinical evidence suggests that JAK inhibition preserves GVL activity. Here we provide an overview of potential roles for JAK signaling in the pathogenesis of acute and chronic GVHD as well as effects on GVL activity. We also review preclinical and clinical results with JAK inhibitors in acute and chronic GVHD settings, with added focus on those actively being evaluated in patients with acute and chronic GVHD.

show abstract

“…These authors also reported a potent reduction of GVHD symptoms and serum cytokines in six patients with acute and chronic steroid-refractory GVHD [ 133 ]. Maffini et al described a patient with steroid-refractory grade IV acute GVHD treated with ruxolitinib with complete resolution of symptoms [ 134 ]. Additionally, Zeiser et al carried out a retrospective multicenter survey with 95 GVHD steroid-refractory patients treated with ruxolitinib, and showed overall and complete response rates of 81.5 and 46.3%, respectively, for acute GVHD, and 85.4 and 7.3%, respectively, for chronic GVHD [ 135 ].…”

Section: Treatmentmentioning

confidence: 99%

Cutaneous Graft-Versus-Host Disease: Diagnosis and Treatment

et al. 2017

View full text Add to dashboard Cite

Graft-versus-host disease (GVHD) is an immunological reaction and a frequent complication following allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and may have a significant negative impact on the patient’s quality of life, particularly in the chronic-stage setting. Many different organs can be involved, which leads to a wide range of clinical manifestations. In this context, dermatologists play a key role by diagnosing and treating GVHD from the outset since cutaneous features are not just the most common but are also usually the presenting sign. Several skin-direct therapies are available and may be indicated as monotherapy or adjuvant treatment in order to allow faster tapering and withdrawal of systemic immunosuppression. Treatment of steroid-refractory patients remains a challenge and, to date, no consensus has been reached for one single agent in second-line therapy. This article aims to review skin involvement as well as provide and update discussion on therapeutic options for both acute and chronic cutaneous GVHD.

show abstract

Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

Cited by 20 publications

References 28 publications

Ruxolitinib for the Treatment of Patients with Steroid-Refractory GVHD: An Introduction to the REACH Trials

Ruxolitinib for the Treatment of Patients with Steroid-Refractory GVHD: An Introduction to the REACH Trials

The Role of Janus Kinase Signaling in Graft-Versus-Host Disease and Graft Versus Leukemia

Cutaneous Graft-Versus-Host Disease: Diagnosis and Treatment

Contact Info

Product

Resources

About