Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review

Fløisand, Yngvar; Lazarevic, Vladimir; Maertens, Johan; Mattsson, Jonas; Shah, Nirav N.; Zachée, Pierre; Taylor, Aliki; Akbari, Mona; Quadri, Syed M.; Parfionovas, Andrejus; Chen, Yi Bin

doi:10.1016/j.bbmt.2018.11.013

Cited by 48 publications

(40 citation statements)

References 44 publications

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“…Nonetheless, clinical outcomes observed in REACH1 are encouraging in the context of historical data. The 42.6% 1-year OS rate for all patients receiving ruxolitinib was comparable or favorable to 1year OS rates among patients treated with vedolizumab (47%), 30 antithymocyte globulin (39%), 21 brentuximab vedotin (38%), 24 or infliximab (;10%). 23 Mesenchymal stem cells have been studied extensively in steroid-refractory aGVHD, with varying response rates.…”

Section: Probability Of Survivalmentioning

confidence: 69%

Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial

Jagasia

Perales

Schroeder

et al. 2020

Blood

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177

137

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Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.

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Section: Probability Of Survivalmentioning

confidence: 69%

Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial

Jagasia

Perales

Schroeder

et al. 2020

Blood

Self Cite

177

137

View full text Add to dashboard Cite

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“…Most importantly, this analysis further emphasizes the disappointing results from current steroid-refractory aGVHD treatments and the need for novel therapeutics. Several such therapies are being tested in clinical trials [22,23].…”

Section: Discussionmentioning

confidence: 99%

Outcomes and Predictors of Response in Steroid-Refractory Acute Graft-versus-Host Disease

Rashidi

DeFor

Holtan

et al. 2019

Biology of Blood and Marrow Transplantation

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The prognosis of steroid-refractory acute graft-versus-host disease (aGVHD) is poor, and predictors of response and survival are unclear. In an exploratory analysis of 203 steroid-refractory aGVHD patients with prospectively collected GVHD data who received antithymocyte globulin, etanercept, or mycophenolate mofetil (MMF) as second-line treatment, we determined the predictors of day 28 response, 2-year overall survival, and 2-year nonrelapse mortality (NRM). To minimize the risk of finding false-positive results, we used least absolute shrinkage and selection operator regression, aggressively eliminating variables that are unlikely to be associated with outcome. Day 28 response to second-line therapy was 38% (complete response, 23%), with a 2-year overall survival of 25% and a 2-year NRM of 62%. Factors associated with response were GVHD prophylaxis, organ involvement, and initial aGVHD to steroid-refractory aGVHD interval. Specifically, compared with cyclosporine/MMF as GVHD prophylaxis, the odds ratio (OR) for calcineurin inhibitor/methotrexate was .8 and for cyclosporine/prednisone .6. The OR for aGVHD to steroid-refractory aGVHD interval 14 versus <14 days was 1.3. The ORs for skin only involvement and gut or liver only involvement when compared with multiorgan involvement were 1.4 and 1.2, respectively. The only variable associated with worse survival was age, with a hazard ratio (HR) per decade of 1.04 for overall mortality. Similarly, age was the only variable associated with NRM (HR per decade, 1.02). When compared with complete response, no response at day 28 increased the risk of death (HR, 2.4; 95% confidence interval, 1.5 to 3.7). In conclusion, by means of an underused statistical technique in the field of transplantation, we identified predictors of response and survival in steroid-refractory aGVHD. Our results highlight the importance of developing novel treatment strategies because current treatments yield poor outcomes.

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“…In an international, retrospective review to evaluate the off-label use of vedolizumab (n=29), ORR was 64% and OS at 6 months was 54%. 95 CMV reactivation and Clostridium difficile colitis were noted. Natalizumab, a selective a4 subunit adhesion molecule inhibitor was studied in a phase II study with a response rate of approximately 30%.…”

Section: Targeting Lymphocyte Traffickingmentioning

confidence: 99%

Translational and clinical advances in acute graft-versus-host disease

Gooptu

Koreth

2020

haematol

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Acute graft-versus-host disease (aGvHD) is induced by immunocompetent alloreactive T lymphocytes in the donor graft responding to polymorphic and non-polymorphic host antigens and causing inflammation in primarily the skin, gastrointestinal tract and liver. aGvHD remains an important toxicity of allogeneic transplantation, and the search for better prophylactic and therapeutic strategies is critical to improve transplant outcomes. In this review, we discuss the significant translational and clinical advances in the field which have evolved based on a better understanding of transplant immunology. Prophylactic advances have been primarily focused on the depletion of T lymphocytes and modulation of T-cell activation, proliferation, effector and regulatory functions. Therapeutic strategies beyond corticosteroids have focused on inhibiting key cytokine pathways, lymphocyte trafficking, and immunologic tolerance. We also briefly discuss important future trends in the field, the role of the intestinal microbiome and dysbiosis, as well as prognostic biomarkers for aGvHD which may improve stratification-based application of preventive and therapeutic strategies.

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Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review

Cited by 48 publications

References 44 publications

Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial

Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial

Outcomes and Predictors of Response in Steroid-Refractory Acute Graft-versus-Host Disease

Translational and clinical advances in acute graft-versus-host disease

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