Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults

Moiseev, Ivan S.; Morozova, Еlena V.; Bykova, T A; Паина, О. В.; Smirnova, Anna G.; Dotsenko, Anna A.; Borzenkova, E.; Галимов, А. Н.; Gudognikova, Ya V; Ekushov, Kirill Alexandrovich; Kozhokar, P.V.; Osipova, Anna A.; Pirogova, Olga V.; Rudakova, Tatiana A.; Klimova, Olesya; Tsvetkov, Nikolai; Кулагин, Е. А.; Суркова, Е. А.; Лапин, С. В.; Родионов, Г. Г.; Moiseev, S I; Serov, Yu A; Zubarovskaya, Ludmila; Afanasyev, Boris

doi:10.1038/s41409-020-0834-4

Cited by 28 publications

(49 citation statements)

References 36 publications

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“…Moreover, in most studies, the mouth and skin were always the best-responding organs. The liver and lung were reported to be the organs with the worst response to ruxolitinib therapy (28)(29)(30). Additionally, the ORR in the gut, liver and lung was the lowest, and patients with liver and lung cGVHD had the longest response times in this study.…”

Section: Discussionmentioning

confidence: 55%

“…Additionally, the ORR in the gut, liver and lung was the lowest, and patients with liver and lung cGVHD had the longest response times in this study. Moreover, Moiseev et al (29) and Streiler et al (31) both reported that ruxolitinib significantly improved the respiratory function of patients with cGVHD, reduced steroid requirements and stabilized lung function in patients with bronchiolitis obliterans as a manifestation of cGVHD.…”

Section: Discussionmentioning

confidence: 99%

“…Hemocytopenia was the most common adverse event observed in this study of patients with cGVHD, consistent with previously reported data. In addition, Moiseev et al (29) claimed that the severity of neutropenia and thrombocytopenia was affected by CMV reactivation (P=0.07), treatment with ganciclovir (P=0.0006), and a higher initial steroid dose (P=0.0017). Gonzaĺez Vicent et al (25) also determined that the incidence of neutropenia was related to the appearance of CMV and treatment with ganciclovir.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Moiseev et al. ( 29 ) and Streiler et al. ( 31 ) both reported that ruxolitinib significantly improved the respiratory function of patients with cGVHD, reduced steroid requirements and stabilized lung function in patients with bronchiolitis obliterans as a manifestation of cGVHD.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Moiseev et al. ( 29 ) claimed that the severity of neutropenia and thrombocytopenia was affected by CMV reactivation ( P =0.07), treatment with ganciclovir ( P =0.0006), and a higher initial steroid dose ( P =0.0017). González Vicent et al.…”

Section: Discussionmentioning

confidence: 99%

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Efficiency and Toxicity of Ruxolitinib as a Salvage Treatment for Steroid-Refractory Chronic Graft-Versus-Host Disease

et al. 2021

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Graft-versus-host disease (GVHD), especially steroid-refractory GVHD, remains a life-threatening complication after hematopoietic stem cell transplantation (HSCT). The effect of the JAK1/2 kinase inhibitor ruxolitinib on treating steroid-refractory acute GVHD has been verified by the REACH1/2 study; however, its safety and efficacy in patients with steroid-refractory chronic GVHD (SR-cGVHD) remain unclear. In this retrospective study, 70 patients received ruxolitinib as a salvage therapy for SR-cGVHD. Twenty-four weeks after ruxolitinib treatment, the overall response rate (ORR) was 74.3% (52/70), including 34 patients who achieved complete remission (CR) and 18 who achieved partial remission (PR). The main adverse event was cytopenia, which occurred in 51.4% (36/70) of patients. After ruxolitinib treatment, the percentage of CD4 cells increased from 18.20% to 23.22% (P<0.001), while the percentages of NK (CD16+CD56+) cells and regulatory T cells (CD4+CD127 ± CD25+) decreased (P<0.001, P<0.001). Among the B cell subsets, the proportion of total B cells approximately tripled from 3.69% to 11.16% (P<0.001). Moreover, we observed a significant increase in IL-10 levels after ruxolitinib treatment (P=0.025) and a remarkable decrease in levels of suppression of tumorigenicity 2 (ST2) from 229.90 ng/ml to 72.65 ng/ml. The median follow-up after the initiation of ruxolitinib treatment was 401 (6-1076) days. The estimated one-year overall survival rate of the whole group was 66.0% (54.4–77.6%, 95% CI), and the one-year overall survival rate of patients with mild and moderate cGVHD was 69.6% (57.4–81.8%, 95% CI), which was better than that of patients with severe cGVHD (31.3%, 0.0–66.2%, 95% CI) (P=0.002). Patients who achieved a CR and PR achieved better survival outcomes (84.5%, 73.9–95.1%, 95% CI) than those who showed NR to ruxolitinib treatments (16.7%, 0–34.3%, 95% CI) (P<0.001). At the final follow-up, cGVHD relapse occurred in six patients after they reduced or continued their ruxolitinib doses. Collectively, our results suggest that ruxolitinib is potentially a safe and effective treatment for SR-cGVHD.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficiency and Toxicity of Ruxolitinib as a Salvage Treatment for Steroid-Refractory Chronic Graft-Versus-Host Disease

et al. 2021

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Graft-Versus-Host Disease (GvHD)

Murray

Stringer

Hutt

2023

The European Blood and Marrow Transplantation Textbook for Nurses

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Acute and chronic graft-versus-host disease (GvHD) is a major cause of morbidity and mortality in patients who undergo allogeneic haematopoietic cell transplantation (HCT) and affects approximately 30–40% of recipients. Prevention remains the goal, and the recent introduction of post-transplant cyclophosphamide in the haploidentical transplant setting is changing the landscape. GvHD diagnosis is complicated, and grading and staging vary depending upon the tool and transplant centre involved. For the majority of patients who go on to develop GvHD, corticosteroids remain the first-line treatment for both acute and chronic forms of the disease. Recipients that are refractory to systemic steroids have a plethora of second- and third-line options available to them. A ‘standard of care’ approach has not yet become agreed globally due to poor evidence from small and limited randomised control trials. However, the recent REACH (Zeiser et al. N Engl J Med. 382(19):1800–10, 2020; Zeiser et al. N Engl J Med. 385(3):228–38, 2021) and ROCKstar trials (Cutler et al. Blood. 38(22):2278–89, 2021) have armed clinicians with new and effective therapies. Supportive care is paramount, and the nurse is at the centre of the patient’s care and in the best position to guide and advise the patient and family through this often-long-term complication.

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Ruxolitinib in the management of steroid-resistant/-dependent acute and chronic graft-versus-host disease: results of routine practice in an academic centre

et al. 2021

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Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults

Cited by 28 publications

References 36 publications

Efficiency and Toxicity of Ruxolitinib as a Salvage Treatment for Steroid-Refractory Chronic Graft-Versus-Host Disease

Efficiency and Toxicity of Ruxolitinib as a Salvage Treatment for Steroid-Refractory Chronic Graft-Versus-Host Disease

Graft-Versus-Host Disease (GvHD)

Ruxolitinib in the management of steroid-resistant/-dependent acute and chronic graft-versus-host disease: results of routine practice in an academic centre

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