Etanercept for steroid-refractory acute graft versus host disease following allogeneic hematopoietic stem cell transplantation

Park, Joo Han; Lee, Hyo‐Jung; Kim, Sei Rhan; Song, Ga Won; Lee, Seung Kyong; Park, Sun Young; Kim, Ki Chan; Hwang, Sun Hyuk; Park, Joon Seong

doi:10.3904/kjim.2014.29.5.630

Cited by 28 publications

(17 citation statements)

References 19 publications

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“…recorded in 24% of patients. Other studies in patients with SR aGVHD have reported variable rates of infections, including 83% to 100% (34% to 40% fatal) in patients receiving infliximab [15,36,37], 78% to 100% (8% to 50% fatal) in patients receiving alemtuzumab [14,[38][39][40][41][42], and 67% (12% fatal) in patients receiving etanercept [43]. However, many of those series did not categorize infections by severity.…”

Section: Discussionmentioning

confidence: 99%

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

Fløisand

Lazarevic

Maertens

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C T Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignancies but carries a significant risk of graft-versus-host disease (GVHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GVHD (aGVHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treating SR GI aGVHD. Data were collected from patients' medical records; criteria for extraction included no more than 1 allo-HCT and at least 1 dose of vedolizumab as treatment for SR GI aGVHD (ie, stage 1 to 4 GI aGVHD following 1 previous treatment regimen(s) containing 1 mg/kg methylprednisolone or equivalent). Descriptive analyses of response rate, overall survival (OS), and serious adverse effects (SAEs) were performed. Twenty-nine patients were identified from 7 sites who had received 1 to 10 doses of vedolizumab 300 mg i.v. (median 3 doses) as treatment for SR GI aGVHD. The overall response rate at 6 to 10 weeks after vedolizumab initiation was 64%, and OS at 6 months was 54%. There were 29 SAEs, including 12 infections; 3 SAEs were considered possibly related to vedolizumab, 2 of which were infections. Thirteen SAEs were fatal, 1 of which was possibly vedolizumabrelated. There were 8 nonserious infections and 1 serious infection with confirmed GI origin in 8 patients; there was no apparent pattern in the timing of these infections relative to the initiation of vedolizumab treatment. Further data on the efficacy and safety of vedolizumab in this setting from prospective trials are needed.

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Section: Discussionmentioning

confidence: 99%

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

Fløisand

Lazarevic

Maertens

et al. 2019

Biology of Blood and Marrow Transplantation

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“…In our recently published study [14], 40% of the children who developed SR aGVHD died of disease-related complications. To our knowledge, this is the largest study on treatment with ET for SR aGVHD in pediatric population [6,[15][16][17]. The majority of studies were conducted in adults, and ET was often associated with other immunosuppressive therapies, such as daclizumab and IL-2 [18], ATG, and tacrolimus [5].…”

Section: Discussionmentioning

confidence: 99%

Etanercept as Treatment of Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients

Faraci

Calevo

Giardino

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C T Corticosteroids are the standard of care for first-line treatment of patients who develop grade II-IV of acute graftversus-host disease (aGVHD), but the optimal second-line treatment has not yet been determinedD 1 5 X X. We prospectively evaluated the use of the anti-TNFa monoclonal antibody etanercept (ET) as second-line treatment in children with steroid-refractory (SR) aGVHD. Twenty-five children with either malignant or nonmalignant diseases experiencing grade II-IV SR aGVHD received ET as second-line treatment. ET was administered after a median of 14 days (range, 5 to 135 days) from the onset of aGVHD. Seventeen out of 25 patients (68%) developed a complete response (CR) or partial response (PR) to ET. The oD 1 6 X Xverall response rate (CR plus PR) was 78% in patients with cutaneous SR aGVHD, 78% in those with gastrointestinal aGVHD, and 57% in those with hepatic aGVHD. On day +100 after the start of ET, 52% of the children were in CR, 16% were in PR, and the remaining 32% failed to respond. Overall survival was 76.5% in responders and 16.7% in nonresponders (P = .004). Transplantation-related mortality at 5 years was 34.1% (95% confidence interval, 18.6% to 57.1%). In our experience, ET has proven to be effective as second-line treatment in children with SR aGVHD.

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“…However, mycophenolate mofetil failed to prove any benefit in the subsequent multicenter, randomized, double-blinded, and placebo-controlled phase 3 trial evaluating its addition to standard corticosteroids ( 63 ). In the setting of steroid-refractory aGVHD, two small single center studies have shown only a modest effect of etanercept with few complete responses ( 64 , 65 ). As for infliximab, efficacy seemed to be higher in case of gut involvement.…”

Section: Hope and Disappointment In Targeting Tnf In Gvhdmentioning

confidence: 99%

Tumor Necrosis Factor α and Regulatory T Cells in Oncoimmunology

et al. 2018

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Tumor necrosis factor α (TNF) is a potent pro-inflammatory cytokine that has deleterious effect in some autoimmune diseases, which led to the use of anti-TNF drugs in some of these diseases. However, some rare patients treated with these drugs paradoxically develop an aggravation of their disease or new onset autoimmunity, revealing an immunosuppressive facet of TNF. A possible mechanism of this observation is the direct and positive effect of TNF on regulatory T cells (Tregs) through its binding to the TNF receptor type 2 (TNFR2). Indeed, TNF is able to increase expansion, stability, and possibly function of Tregs via TNFR2. In this review, we discuss the role of TNF in graft-versus-host disease as an example of the ambivalence of this cytokine in the pathophysiology of an immunopathology, highlighting the therapeutic potential of triggering TNFR2 to boost Treg expansion. We also describe new targets in immunotherapy of cancer, emphasizing on the putative suppressive effect of TNF in antitumor immunity and of the interest of blocking TNFR2 to regulate the Treg compartment.

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Etanercept for steroid-refractory acute graft versus host disease following allogeneic hematopoietic stem cell transplantation

Cited by 28 publications

References 19 publications

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

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

Etanercept as Treatment of Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients

Tumor Necrosis Factor α and Regulatory T Cells in Oncoimmunology

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