Ruxolitinib in steroid-refractory chronic graft-versus-host disease: experience of a single center

Ferreira, Adriano Martison; Silva, Carolina Atallah Pontes da; Pereira, Andréa Z; Szor, Roberta Shcolnik; Fonseca, Ana Rita Brito Medeiros da; Serpa, Mariana; Xavier, Erick Menezes; Melo, Michelly Kerly Sampaio de; Novis, Yana; Tucunduva, Luciana; Rocha, Vanderson; Arrais‐Rodrigues, Celso

doi:10.1038/s41409-017-0068-2

Cited by 24 publications

(18 citation statements)

References 12 publications

(18 reference statements)

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“…At baseline, the majority of our cohort had moderate to severe disease that failed to improve with multiple previous therapies. In particular, the majority of patient with skin involvement had severe skin disease and fibrosis, which may explain why our overall response rate was lower than previously reported by Khoury et al [11], Ferreira et al [12], and Zeiser et al [14].…”

Section: Discussioncontrasting

confidence: 70%

“…The potential benefit of ruxolitinib in refractory cGVHD was first demonstrated in a 2015 retrospective analysis of 41 patient that found a high overall response rate of 85% [9]. Since then, reports of ruxolitinib impact have been limited to small case series and a retrospective analysis [4,11,12].…”

Section: Discussionmentioning

confidence: 99%

“…Responses occurred early and were sustained, which enabled discontinuation of treatment in 68% of patients or reduction of steroids to physiological doses in 21% of patients. Another report retrospectively evaluating off-label use of ruxolitinib in 20 patients with cGVHD reported a slightly lower overall response rate of 75% [12].…”

Section: Introductionmentioning

confidence: 97%

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Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease

Modi

Hernandez-Henderson

Yang

et al. 2019

Biology of Blood and Marrow Transplantation

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Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease

Modi

Hernandez-Henderson

Yang

et al. 2019

Biology of Blood and Marrow Transplantation

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“…This observation has been translated into the clinic with experiences in adults that demonstrate an ORR of nearly 80% with ruxolitinib in SR‐GvHD and also in children, but with worst results …”

Section: Discussionmentioning

confidence: 98%

“…Khoury et al and Ferreira et al collected results of about 20 patients each, treated with ruxolitinib only by chronic GvHD, being high the response rate, of 100% and 75% respectively, although most are PR.…”

Section: Discussionmentioning

confidence: 99%

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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Evolving Therapeutic Options for Chronic Graft‐versus‐Host Disease

Gonzalez

Pidala

2020

Pharmacotherapy

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Despite improvements in prevention and treatment of acute graft‐versus‐host disease (GVHD), chronic GVHD (cGVHD) remains a significant contributor to morbidity and mortality of allogeneic transplant patients. Chronic GVHD remains a leading cause of late complications posttransplant and is impacted by donor‐, patient‐, and transplant‐related (hematopoietic cell transplant [HCT]) factors. Advances in the biological understanding of cGVHD have provided opportunities to improve clinical interventions for prevention and treatment. Expansion of posttransplantation cyclophosphamide beyond haploidentical HCTs has transformed alternative donor, matched, and mismatch GVHD outcomes and is currently being investigated in two upcoming clinical trials network prophylaxis studies. Although corticosteroids remain the cornerstone therapy, several clinical trials are prospectively investigating the utility of using novel agents in combination with corticosteroids as upfront therapy to mitigate prolonged steroid exposure. Several treatment options for patients with steroid‐refractory cGVHD are currently being investigated, and advances have resulted in ibrutinib becoming the first cGVHD agent approved by the U.S. Food and Drug Administration. We review recent advances in understanding of cGVHD pathophysiology and new approaches for the prevention and treatment of cGVHD.

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Ruxolitinib in steroid-refractory chronic graft-versus-host disease: experience of a single center

Cited by 24 publications

References 12 publications

Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease

Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease

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

Evolving Therapeutic Options for Chronic Graft‐versus‐Host Disease

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