Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis

Maldonado, Mauricio; Villanueva, Pablo; Cortés-Monroy, Pablo Bertín; Arias, Veronica Jara; Donoso, Katherine Soto; González, Pablo Uribe; Tachini, Mauricio Ocqueteau; Pérez-Simón, Josè Antonio

doi:10.1186/s40164-017-0092-3

Cited by 34 publications

(12 citation statements)

References 18 publications

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“…In vitro, T cells exposed to ruxolitinib had reduced proliferation and cytokine production in response to alloantigen , and in vivo treatment with ruxolitinib reduced GVHD severity in treatment‐naive and steroid‐refractory major histocompatibility complex–mismatched murine models . In published case series and retrospective reviews, complete response (CR) rates of 8%–46% and overall response rates (ORR) of 38%–82% were reported for adult and pediatric patients with aGVHD refractory to steroids alone or in addition to other immunosuppressive drugs . Herein we provide a summary of the Food and Drug Administration's (FDA's) review of ruxolitinib for treatment of SR‐aGVHD based on the first prospective trial, the REACH‐1 Study.…”

Section: Introductionmentioning

confidence: 99%

FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease

et al. 2019

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On May 24, 2019, the Food and Drug Administration approved ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-271 (REACH-1; NCT02953678), an open-label, single-arm, multicenter trial that included 49 patients with grades 2-4 SR-aGVHD occurring after allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered at 5 mg twice daily, with dose increases to 10 mg twice daily permitted after 3 days in the absence of toxicity. The Day-28 overall response rate was 57.1% (95% confidence interval [CI]: 42.2-71.2). The median duration of response was 0.5 months (95% CI: 0.3-2.7), and the median time from Day-28 response to either death or need for new therapy for acute GVHD was 5.7 months (95% CI: 2.2 to not estimable). Common adverse reactions included anemia, thrombocytopenia, neutropenia, infections, edema, bleeding, and elevated transaminases. Ruxolitinib is the first drug approved for treatment of SR-aGVHD. The Oncologist 2020;25:e328-e334Implications for Practice: Ruxolitinib is the first Food and Drug Administration-approved treatment for steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older. Its approval provides a treatment option for the 60% of those patients who do not respond to steroid therapy.

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Section: Introductionmentioning

confidence: 99%

FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease

et al. 2019

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“…Ibrutinib is a combined BTK/ITK inhibitor known to be efficacious in treatment of murine and human cGVHD, for which it is currently the only FDA-approved drug (42, 43). The Jak1/Jak2 inhibitor, ruxolitinib has been in case studies and is currently in Phase 2 and 3 clinical trials for use in steroid-refractory cGVHD (44–46). Mast cells express many of the signaling molecules targeted by these drugs, and we therefore investigated whether chemokine production would be inhibited when treated with ibrutinib or ruxolitinib (47, 48).…”

Section: Discussionmentioning

confidence: 99%

Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease

et al. 2019

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Allogeneic hematopoietic stem cell transplant (allo-HSCT) is often used to treat acute leukemia or defects of hematopoiesis. Its widespread use is hampered by graft-vs.-host disease (GVHD), which has high morbidity and mortality in both acute and chronic subtypes. Chronic GVHD (cGVHD) occurs most frequently in skin and often is characterized by pathogenic fibrosis. Mast cells (MCs) are known to be involved in the pathogenesis of other fibrotic diseases. In a murine model of cGVHD after allo-HSCT, C57BL/6J recipients of allogeneic LP/J donor cells develop sclerodermatous dermal cGVHD which is significantly decreased in mast cell-deficient B6.Cg-KitW−sh/HNihrJaeBsmGlliJ recipients. The presence of MCs is associated with fibrosis, chemokine production, and recruitment of GVHD effector cells to the skin. Chemokine production by MCs is blocked by drugs used to treat cGVHD. The importance of MCs in skin cGVHD is mirrored by increased MCs in the skin of patients with dermal cGVHD. We show for the first time a role for MCs in skin cGVHD that may be targetable for preventive and therapeutic intervention in this disease.

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“…Zeiser et al reported in their landmark paper data from 95 patients with steroid-refractory acute (n=54) and chronic (n=41) GvHD and described for both groups a response rate above 80% [5]. Other investigators published data from 8 to 13 patients: Maldonado et al described in eight younger patients with acute and chronic GvHD a response rate of 100% (CR n=3, PR n=5) and Assouan et al were successful with a partial or complete remission in 7/10 patients [9, 10]. Another group described use of ruxolitinib for GvHD treatment in paediatric patients suffering from acute GvHD [11].…”

Section: Discussionmentioning

confidence: 99%

Ruxolitinib for Therapy of Graft-versus-Host Disease

Neumann

Schneidewind

Weigel

et al. 2019

BioMed Research International

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Objective. Steroid-resistant graft-versus-host disease (GvHD) is a major challenge after allogeneic stem cell transplantation and associated with significant morbidity and mortality. There is no therapeutic standard defined beyond calcineurin inhibitors (CNI) and steroids. Furthermore, some patients may have contraindications against CNI or high-dose steroids. Efficacy of ruxolitinib against GvHD has been described recently. Methods. Ruxolitinib was used for treatment of acute or chronic GvHD in eight patients. The patients either needed intensification of therapy or had contraindications against use of CNI or high-dose steroids. Results. Supplementation of therapy in acute GvHD with severe diarrhea with ruxolitinib was unsuccessful. All these patients died from acute GvHD. Introduction of ruxolitinib into therapy and relapse prophylaxis in other patients was successful in 4/4 cases (CR=3, PR=1). Indications for ruxolitinib were contraindications against CNI due to aHUS in two cases and the need for steroid sparing in two other cases. None of these patients suffered from diarrhea at the initiation of ruxolitinib. Conclusion. Ruxolitinib was effective for therapy of acute and chronic GvHD in higher lines in patients without severe diarrhea. Ruxolitinib could replace successfully CNI and high-dose steroids. Further investigations are necessary to define the position of ruxolitinib in GvHD-therapy.

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Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis

Cited by 34 publications

References 18 publications

FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease

FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease

Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease

Ruxolitinib for Therapy of Graft-versus-Host Disease

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