Anti-α4β7 integrin monoclonal antibody (vedolizumab) for the treatment of steroid-resistant severe intestinal acute graft-versus-host disease

Danylesko, Ivetta; Bukauskas, Adomas; Paulson, Martin; Pečeliūnas, Valdas; d.y, Tobias Gedde-Dahl; Shimoni, Avichai; Shouval, Roni; Griškevičius, Laimonas; Fløisand, Yngvar

doi:10.1038/s41409-018-0364-5

Cited by 44 publications

(45 citation statements)

References 33 publications

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“…By inhibiting a 4 b 7 integrin, vedolizumab may interfere with gut-selective T lymphocyte trafficking, and it may be a treatment option for patients with SR GI aGVHD. This has led some clinicians to use vedolizumab off-label in these patients, and published case series have suggested clinical activity in patients with GI aGVHD [27][28][29][30]. The aims of this international, retrospective record review were to further evaluate the real-world use of vedolizumab in the off-label setting for treating patients with SR GI aGVHD, and also to assess key clinical outcomes in these patients, including those related to the safety and effectiveness of vedolizumab therapy.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…Allogeneic HSCT practices changed dramatically over time. 37 and anti-integrin antibodies, 39 while mesenchymal stem cells 40 have already become an integral part of the treatment of GvHD in many centers in pediatric patients.…”

Section: Discussionmentioning

confidence: 99%

Steroid‐refractory acute graft‐versus‐host disease graded III‐IV in pediatric patients. A mono‐institutional experience with a long‐term follow‐up

Berger

Pessolano

Carraro

et al. 2020

Pediatric Transplantation

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Despite prophylaxis with immunosuppressive agents, nearly half of patients develop aGvHD after allogeneic hematopoietic cell transplantation (HSCT). 1-3 For decades until now, the first-line treatment of aGvHD has been 1-2 mg/kg/d methylprednisolone or prednisone but, unfortunately, over 30% of patients will not respond to initial treatment with steroids and need secondary treatments. However, despite many studies conducted worldwide, no agents for treatment of steroid-resistant or refractory GvHD have clearly emerged as a gold standard. 4,5 Several factors contribute to the risk and severity of aGvHD: degree of donor-recipient HLA matching, intensity of conditioning regimen, age, previous donor alloimmunization, and GvHD prophylactic regimen. 6 Historical studies reported an overall long-term survival of 10%-25% in patients with severe acute GvHD, defined as overall grade III or IV disease. 7-12 Since then, significant changes in allogeneic HSCT practice have included the introduction of peripheral blood, cord blood, and haploidentical HSCT.

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“…Vedolizumab is a monoclonal antibody that recognizes the integrin α4β7 present on circulating lymphocytes and inhibits their relocation to the gastrointestinal tract [91,92]. Recent case series have reported mixed results for vedolizumab in gastrointestinal SR-aGVHD (Table 2) [91][92][93][94]. Fløisand et al described a case series of six patients with SR-aGVHD with single-site-involvement, in which all patients responded to second-line treatment with vedolizumab; four patients were alive at a median followup of 10 months [92].…”

Section: Vedolizumabmentioning

confidence: 99%

“…The discrepancies in outcomes with vedolizumab treatment for SR-aGVHD may be related to its mechanism of action: Preventing the migration of lymphocytes to the gastrointestinal tract may be effective only at an early stage and not when GVHD is established. A retrospective case series of 29 patients reported significantly better outcomes in patients treated with vedolizumab in the second vs third or higher line (ORR, 13/13 [100%] vs 10/16 [63%]; P = 0.012 and CR, 7/13 [54%] vs 1/16 [6%]; P = 0.005) [94]. Nevertheless, a recent dose-finding, prospective, phase 2 study of vedolizumab in the second line (NCT02993783) was terminated early for lack of efficacy [95].…”

Section: Vedolizumabmentioning

confidence: 99%

Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

2020

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Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the number of patients undergoing alloHCT increases, developing safe and effective treatments for aGVHD will become increasingly important, especially for those whose disease becomes refractory to systemic steroid therapy. This paper reviews current treatment options for patients with steroidrefractory aGVHD and discusses data from recently published clinical studies to outline emerging therapeutic strategies.

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Anti-α4β7 integrin monoclonal antibody (vedolizumab) for the treatment of steroid-resistant severe intestinal acute graft-versus-host disease

Cited by 44 publications

References 33 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

Steroid‐refractory acute graft‐versus‐host disease graded III‐IV in pediatric patients. A mono‐institutional experience with a long‐term follow‐up

Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

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