Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease

Khoury, H. Jean; Langston, Amelia; Kota, Vamsi; Wilkinson, Jennifer A.; Pusic, Iskra; Jillella, Anand; Bauer, Sonja; Kim, Audrey S; Roberts, Danielle; Al-Kadhimi, Zaid; Bodó, Imre; Winton, Elliott F.; Arellano, Martha; DiPersio, John F.

doi:10.1038/s41409-017-0081-5

Cited by 78 publications

(66 citation statements)

References 13 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Zeiser et al reported a response rate of 81.5% in patients with steroid‐refractory acute GvHD and 85.4% in patients with chronic GvHD . Khoury et al observed high responses in steroid‐refractory chronic GvHD . Finally, based on the results of REACH1 clinical trial, in which our institution have participated, FDA approved ruxolitinib as the first and only FDA‐approved treatment for steroid‐refractory acute GvHD after alloHCT.…”

Section: Discussionmentioning

confidence: 96%

“…As a result, inhibition of JAK1/2 via ruxolitinib has been explored as a possible treatment for GvHD after alloHCT, based on ruxolitinib's potent GvHD‐sparing effects seen in mouse models . In humans, there have been several reports using ruxolitinib in GvHD following alloHCT . Zeiser et al reported a response rate of 81.5% in patients with steroid‐refractory acute GvHD and 85.4% in patients with chronic GvHD .…”

Section: Discussionmentioning

confidence: 99%

“…Ruxolitinib, a balanced Janus kinase (JAK)‐1/2 inhibitor, is approved for the treatment of myelofibrosis and has been shown to effectively treat, and possibly prevent, GvHD after alloHCT in mice and humans . We report on three cases of GvHD developing after solid organ transplantation treated with ruxolitinib at Washington University School of Medicine in 2017‐2018.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The use of ruxolitinib for acute graft-versus-host disease developing after solid organ transplantation

Jacobs

Olson

Pellini

et al. 2020

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

Development of graft‐versus‐host disease (GvHD) is a rare complication after transfusions or solid organ transplantation. Patients typically present with a skin rash, diarrhea, liver failure, and bone marrow aplasia. A diagnosis of transfusion/transplantation associated‐GvHD is made based on the clinical and histologic evidence, yet it is often delayed due to the nonspecific symptoms attributed to the patient's underlying illness. Several therapeutic approaches are being used including both increasing and withdrawing immunosuppression, and the use of cellular therapies. Unfortunately, the success rate of these approaches is low and the mortality of this complication is very high. New approaches are needed. We report on three cases of GvHD developing after solid organ transplantation treated with ruxolitinib.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The use of ruxolitinib for acute graft-versus-host disease developing after solid organ transplantation

Jacobs

Olson

Pellini

et al. 2020

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, in a moderate/severe cGVHD, ruxolitinib induces high response rates, and reduction to physiologic doses/discontinuation of prednisone was possible in 90% of patients at a median of 106 days (range, 31-365) from starting ruxolitinib [4,5]. In conclusion, ruxolitinib appears to be a viable treatment option for SR-aGVHD.…”

Section: Dear Editorsmentioning

confidence: 87%

“…Our study did not have explicit eligibility criterion and may reflect more real-world use of ruxolitinib for SR-aGVHD. Several patients were given very short durations of ruxolitinib < 14 days before transitioning to comfort care or expiring, and these patients were excluded as response was difficult to assess and likely does not reflect the efficacy of ruxolitinib.Additionally, in a moderate/severe cGVHD, ruxolitinib induces high response rates, and reduction to physiologic doses/discontinuation of prednisone was possible in 90% of patients at a median of 106 days (range, 31-365) from starting ruxolitinib [4,5]. In conclusion, ruxolitinib appears to be a viable treatment option for SR-aGVHD.ª 2019 Steunstichting ESOT…”

mentioning

confidence: 94%

Ruxolitinib for steroid‐refractory acute graft‐versus‐host disease

et al. 2019

Self Cite

View full text Add to dashboard Cite

Dear EditorsCorticosteroids are still the standard initial therapy for acute graft-versus-host-disease (aGVHD), but are effective in only approximately half of cases [1]. Many treatment options have been tested and used as second line, but none have been established yet as the standard of care.Our institution has been using ruxolitinib for steroidrefractory aGVHD (SR-aGVHD), as well as chronic GVHD, for the past several years. We conducted a retrospective review (approved by IRB) of patients who were treated with ruxolitinib for SR-aGVHD over a 2-year period (2015-2016). SR-aGVHD was defined as no response in any stage of GVHD in any organ after 5 days of steroids initiation or worsening GVHD stage in any organ after 3 days of steroids. Primary aGVHD and aGVHD/chronic GVHD (cGVHD) overlap were both included. We defined high-risk acute GVHD by using acute GVHD risk score refined by Minnesota group [2]. Only patients who received> 14 days of ruxolitinib were considered evaluable for response assessment.Thirty-six patients were included in the analysis described in Table 1. Methylprednisolone 2 mg/kg/day was used as initial steroid in most patients; however, different doses were used at the physician discretion. Twenty-four patients (67%) received at least 14 days of treatment and were evaluable for response; the overall response rate (ORR) was 58% (95% CI 38%-78%) with 25% obtaining a complete (CR). Of those who were evaluable for response, the median overall survival (OS) was 7.4 months (95% CI UTQ-15.9) for responders compared with 0.9 months (95% CI 0.7-1.1) for nonresponders (P < 0.001). The relapse rate of primary disease was 8%; one patient relapsed while on ruxolitinib and two within 6 months following discontinuation. Ruxolitinib was well tolerated; hematologic toxicity was generally mild, and there were no cases of treatment-related mortality reported.The data presented herein are similar to what was recently reported from the REACH1 trial [3]. However, in our study, SR-aGVHD was defined as worsening disease after 3 days of steroids or no improvement in 5 days versus 3 days or 7 days, respectively, in REACH1. In addition, we included patients who received numerous prior treatments for SR-aGVHD, while REACH1 only allowed patients to receive calcineurin inhibitors. Thus, our patients were more heavily treated which may account for differences in response rates; in our study, the ORR was 58% with 25% CR compared to 73% with 56% CR in REACH1. Our study did not have explicit eligibility criterion and may reflect more real-world use of ruxolitinib for SR-aGVHD. Several patients were given very short durations of ruxolitinib < 14 days before transitioning to comfort care or expiring, and these patients were excluded as response was difficult to assess and likely does not reflect the efficacy of ruxolitinib.Additionally, in a moderate/severe cGVHD, ruxolitinib induces high response rates, and reduction to physiologic doses/discontinuation of prednisone was possible in 90% of patients at a median of 106 days (range...

show abstract

Evaluation of Ruxolitinib for Steroid-Refractory Chronic Graft-vs-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Shi

Luo

et al. 2021

JAMA Netw Open

View full text Add to dashboard Cite

Key Points Question Is ruxolitinib an option for patients with steroid-refractory chronic graft-vs-host disease, and what characteristics are associated with treatment response? Findings In this case series of 41 patients with steroid-refractory chronic graft-vs-host disease who were treated with ruxolitinib, heavily pretreated patients could achieve meaningful responses with a favorable safety profile. No lung involvement and haploidentical donors were associated with response to ruxolitinib. Meaning In this study, monotherapy with ruxolitinib was associated with a meaningful response in patients with steroid-refractory chronic graft-vs-host disease, suggesting a possible therapeutic option for a serious disease with no currently accepted standard-of-care treatment.

show abstract

Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease

Cited by 78 publications

References 13 publications

The use of ruxolitinib for acute graft-versus-host disease developing after solid organ transplantation

The use of ruxolitinib for acute graft-versus-host disease developing after solid organ transplantation

Ruxolitinib for steroid‐refractory acute graft‐versus‐host disease

Evaluation of Ruxolitinib for Steroid-Refractory Chronic Graft-vs-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Contact Info

Product

Resources

About