Efficacy of the interleukin‐2 receptor antagonist basiliximab in steroid‐refractory acute graft‐<i>versus</i>‐host disease

Schmidt‐Hieber, Martin; Fietz, Thomas; Knauf, Wolfgang; Uharek, Lutz; Hopfenmüller, Werner; Thiel, Eckhard; Blau, Igor Wolfgang

doi:10.1111/j.1365-2141.2005.05631.x

Cited by 85 publications

(79 citation statements)

References 49 publications

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“…16 In previous studies, the chimeric IL-2R antibodies binding with high affinity to the a-chain of the IL-2R, daclizumab, or basiliximab were given as a single second-line agent to patients with SR-aGVHD. CR was achieved in 17%-37% of patients and 6-mo OS was poor, at only 28-55%, 10, 17, 18 while 5-y OS was 20%. 11 On the other hand, earlier animal models had suggested that TNF-a played a major role in aGVHD of gastrointestinal (GI) tract and skin.…”

Section: Discussionmentioning

confidence: 94%

“…Acute GVHD involved skin in 54 patients, gut in 59 patients, and liver in 42 patients. The median number of infusions of basiliximab was 4 (range [2][3][4][5][6][7][8][9][10][11], and the median number of etanercept was 9 (range 2-12). At day 28 after the initiation of treatment with the combination of basiliximab and etanercept, the overall response rate (ORR) (CRCPR) to second-line treatment was 90.8% (59/65) including 49 CRs (75.4%).…”

Section: Gvhd Responsementioning

confidence: 99%

“…[6][7][8] Mono-therapy targeting T-cell activation by IL-2R antibody (basiliximab) [9][10][11] or single drug using TNF-a antagonisms (infliximab, etanercept) 12,13 has shown encouraging results in smaller, retrospective studies of patients with SRaGVHD. We hypothesized that the simultaneous blockade of activated T cells and pivotal cytokines may further improve the outcomes of patients with SR-aGVHD.…”

Section: Introductionmentioning

confidence: 99%

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Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Tan

Xiao

et al. 2017

OncoImmunology

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Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2-11) and of etanercept was 9 (range 2-12). At day 28 after starting the combination treatment, overall response (complete and partial response: CRCPR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p D 0.043, RR D 3.169), development of grades III-IV liver aGVHD (p D 0.007, RR D 5.034) and cytomegalovirus (CMV) reactivation (p D 0.035, RR D 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

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Section: Discussionmentioning

confidence: 94%

Section: Gvhd Responsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Tan

Xiao

et al. 2017

OncoImmunology

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“…This was thought to be a result of depletion of Tregs and their regulatory role in aGVHD. Other IL2 antibodies are in clinical trials as well [94,95]. Basiliximab is a shorter acting IL2 receptor antibody.…”

Section: Anti-interleukin 2 Receptor Antibodiesmentioning

confidence: 99%

“…Basiliximab is a shorter acting IL2 receptor antibody. It has been associated with modest responses when used in treatment of aGVHD [95].…”

Section: Anti-interleukin 2 Receptor Antibodiesmentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

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Manifestations and Treatment of Acute Graft‐versus‐Host Disease

Cutler

Antin

2015

Thomas’ Hematopoietic Cell Transplantation

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Efficacy of the interleukin‐2 receptor antagonist basiliximab in steroid‐refractory acute graft‐versus‐host disease

Cited by 85 publications

References 49 publications

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

State-of-the-art acute and chronic GVHD treatment

Manifestations and Treatment of Acute Graft‐versus‐Host Disease

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