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

Jagasia, Madan; Zeiser, Robert; Arbushites, Michael; Delaite, Patricia; Gadbaw, Brian; Bubnoff, Nikolas von

doi:10.2217/imt-2017-0156

Cited by 72 publications

(52 citation statements)

References 47 publications

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“…However, there has been no pharmacokinetic study to determine the best tolerated dose of ruxolitinib in children. Therefore, the recommended doses and approaches in the literature should continue to be used until the results of the REACH trials are disclosed; these trials are currently evaluating the clinical outcomes and pharmacokinetic results of ruxolitinib for GVHD in pediatric and adult patients.…”

Section: Discussionmentioning

confidence: 99%

Ruxolitinib salvage therapy is effective for steroid‐refractory graft‐versus‐host disease in children: A single‐center experience

Uygun

Karasu

Daloğlu

et al. 2020

Pediatric Blood & Cancer

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Background Despite the increasing performance of allogeneic hematopoietic cell transplantation over the last decades, graft‐versus‐host disease (GVHD) remains the main cause of morbidity and mortality. The efficacy of ruxolitinib against GVHD has been demonstrated in adult studies; however, very few studies have been conducted in children. Procedure This study aimed to evaluate the efficacy of ruxolitinib in 29 children with steroid‐refractory acute or chronic GVHD. Twenty‐five (87%) patients received at least three different immune modulator agents, including methylprednisolone, before initiating ruxolitinib. Results All grade 2 acute GVHD patients completely responded to ruxolitinib treatment; 82% of high‐grade (3‐4) acute GVHD patients and 80% of chronic GVHD (moderate‐severe) patients had at least a partial response. Of seven patients with bronchiolitis obliterans, five had a partial response after ruxolitinib. Of 29 patients, 22 were administered steroids at any time in the first month of acute GVHD or the first three months of chronic GVHD during ruxolitinib usage, which was significantly tapered by the end of the observation period. Conclusion Steroid‐refractory acute and chronic pediatric GVHD patients treated with ruxolitinib had a high overall response rate, with the additional benefit of steroid sparing.

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Section: Discussionmentioning

confidence: 99%

Ruxolitinib salvage therapy is effective for steroid‐refractory graft‐versus‐host disease in children: A single‐center experience

Uygun

Karasu

Daloğlu

et al. 2020

Pediatric Blood & Cancer

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“…This observation has been translated into the clinic with experiences in adults and in children that demonstrate an overall response rate (ORR) of nearly 80% with ruxolitinib in SR‐GvHD. These results are impressive in this group of patients and require validation within a clinical trial setting that are now underway …”

Section: Introductionmentioning

confidence: 88%

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

et al. 2018

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Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively.Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 AE 9% and 28 AE 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 AE 11% and 58 AE 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.

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“…In cGVHD, the overall response rate was over 80%, with 36% recurrence of cGVHD at 1 year and durable for 6 months. These responses were seen in both cutaneomucosal and visceral cGVHD . Baricitinib (JAK1/2 inhibitor) and Itacitinib (JAK 1 inhibitor) are currently being studied in the treatment of cGVHD.…”

Section: Janus Kinase Inhibitors: Ruxolitinib Baricitinib and Itacimentioning

confidence: 99%

Advances in the treatment of chronic graft‐versus‐host disease

Johnson

Couriel

2019

Adv Cell Gene Ther

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Chronic Graft Versus Host Disease (cGVHD) occurs in over 50-70% of patients undergoing hematopoietic stem-cell transplantation (HSCT) and is the leading cause of late non-relapse mortality. cGVHD typically has insidious multi-organ involvement and has been associated with a worse quality of life, functional status, and increased risk of subsequent comorbidities. The last several years have seen advances in the understanding of the disease, which provided a framework for the design of translational and clinical studies with newer agents currently at different phases which that may hopefully change the course of the disease. This review provides an overview of more commonly used and newer second line options for the management of cGVHD.

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

Cited by 72 publications

References 47 publications

Ruxolitinib salvage therapy is effective for steroid‐refractory graft‐versus‐host disease in children: A single‐center experience

Ruxolitinib salvage therapy is effective for steroid‐refractory graft‐versus‐host disease in children: A single‐center experience

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

Advances in the treatment of chronic graft‐versus‐host disease

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