Daclizumab as useful treatment in refractory acute GVHD: a paediatric experience

Miano, Maurizio; Cuzzubbo, Daniela; Terranova, Paola; Giardino, Stefano; Lanino, Edoardo; Morreale, Giuseppe; Castagnola, Elio; Dini, Giorgio; Faraci, Maura

doi:10.1038/bmt.2008.331

Cited by 33 publications

(35 citation statements)

References 16 publications

(24 reference statements)

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“…Our study showed response rate of 84.6%, and CR was obtained in 76.9% of patients, which is in line with results obtained in two pediatric studies with daclizumab in steroid-refractory GvHD (11,12). The high response rate to daclizumab in our study on patients with grade IV steroid-refractory aGvHD is in contrary to the conclusions of the previous studies, in which daclizumab proved to be useful in the early grades of aGvHD, but had limited activity in severe ones (8,11,12,19,20).…”

Section: Discussionsupporting

confidence: 91%

“…Considering organ involvement, pediatric experience by Miano et al. (12) demonstrated the efficacy of daclizumab in the treatment of stages I–IV cutaneous aGvHD, stages I–III GI aGvHD, and mild (stage I) hepatic aGvHD, but hepatic and high‐grade intestinal involvement appeared to be less responsive to this treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Daclizumab was also found to be effective as second-line treatment of steroid-resistant GvHD in some reports (9,10,18). Several moderatesized prospective trials and a single-center retrospective study, which are mostly based on adult populations, have been performed to evaluate the efficacy of daclizumab in the treatment of refractory aGvHD (9)(10)(11)(12)(13)(14)18). In these studies, ORRs generally ranged from 40% to 67%, with CR rates of 8-47%.…”

Section: Discussionmentioning

confidence: 99%

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Long‐term follow‐up of children treated with daclizumab for steroid‐refractory gastrointestinal GvHD in a prospective study

Hamidieh

Hadjibabaie

Taghizadeh-Ghehi

et al. 2012

Pediatric Transplantation

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Hamidieh AA, Hadjibabaie M, Taghizadeh Ghehi M, Jalili M, Hosseini A, Pasha F, Behfar M, Ghavamzadeh A. Long‐term follow‐up of children treated with daclizumab for steroid‐refractory GI GvHD in a prospective study. Abstract: Daclizumab, a humanized MoAB to IL‐2Ra, has been found to be safe and effective in adults with refractory GvHD; however, data in children are limited. The aim of this prospective study was to evaluate the long‐term safety and efficacy of daclizumab in children with steroid‐refractory GI aGvHD. This study included 13 children who developed steroid‐refractory GI GvHD between 2007 and 2009. When first‐line treatment failed, daclizumab was given in a regimen of 1 mg/kg intravenously and then repeated on a 10‐ to 14‐day interval for maximum five doses if necessary. Daclizumab was well tolerated, but infections were common. Ten patients responded to daclizumab completely, one patient responded partially, and two patients failed to respond. With a median follow‐up of 630 days, 10 patients were alive and free of severe infections, but among them, four patients were suffering from cGvHD. Of the three remaining patients, one died because of bacterial meningitis, and the other two patients died because of severe refractory GI GvHD. This long‐term evaluation showed that daclizumab could be an effective and relatively safe treatment in most of the pediatric patients with severe steroid‐refractory GI GvHD.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long‐term follow‐up of children treated with daclizumab for steroid‐refractory gastrointestinal GvHD in a prospective study

Hamidieh

Hadjibabaie

Taghizadeh-Ghehi

et al. 2012

Pediatric Transplantation

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“…Alemtuzumab results in an overall response rate of almost 70%, with 40% of patients experiencing a CR. The CR rate is somewhat comparable to other commonly used agents for SR-aGVHD in children, such as infliximab [26], basiliximab [27], and daclizumab [28], with CR rates of 56%, 53%, and 46%, respectively. The response that we observed to alemtuzumab is also comparable to rates noted in the adult literature, with overall responses ranging from 50% to 94% and CR rates ranging from 20% to 40% [15–21,29,30].…”

Section: Discussionmentioning

confidence: 58%

A Prospective Study of Alemtuzumab as a Second-Line Agent for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation

Khandelwal

Emoto

Fukuda

et al. 2016

Biology of Blood and Marrow Transplantation

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We describe a single-center prospective study of alemtuzumab as a second-line agent for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in pediatric and young adult allogeneic hematopoietic stem cell transplant recipients. Alemtuzumab was administered for grades II to IV aGVHD if patients did not improve within 5 days or worsened within 48 hours after corticosteroids. Interim analyses of alemtuzumab levels and response were performed after every 5 patients enrolled, resulting in 3 dosing cohorts, as follows: (1) .2 mg/kg alemtuzumab subcutaneously on days 1 to 5 (maximum of 31 mg over 5 days) and .2 mg/kg/dose (not exceeding 10 mg/dose) on days 15, 22, and 29; (2) .2 mg/kg alemtuzumab subcutaneously on days 1 to 5 (maximum of 43 mg over 5 days) and .2 mg/kg/dose on day 7, 10, 15, 22, and 29; and (3) .2 mg/kg subcutaneously on days 1 to 5 and .2 mg/kg/dose on day 7, 10, 15, and 22. Alemtuzumab levels were assessed before starting alemtuzumab and at days 1, 3, 6, 10, and 14 and weekly until day 99, where day 1 was the day of first alemtuzumab dose. Fifteen patients (median age, 10 years; range, 1.4 to 27) received alemtuzumab for grades II (6%), III (74%), and IV (20%) SR-aGVHD. The overall response rate was 67%, with complete response (CR) in 40%, partial response (PR) in 27%, and no response in 33%. The median day 6 alemtuzumab level was 2.79 µg/mL (interquartile range, 1.34 to 4.89) in patients with CR compared with .62 µg/mL (interquartile range, .25 to 1.45) in patients with PR + no response (P < .05). Ninety percent (n = 9) of patients with a CR or PR reduced corticosteroid doses within 8 weeks from first alemtuzumab dose. Side effects included fever (26%) and transient thrombocytopenia (53%). Asymptomatic viremias occurred in all patients but invasive viral disease occurred in 2 patients. One patient developed Epstein-Barr virus–post-transplantation lymphoproliferative disorder. Eighty percent (n = 12) of patients were alive at 6 months, of whom 53% (n = 8) were free of GVHD whereas 13% (n = 2) developed chronic GVHD. Alemtuzumab is an effective second-line agent for children and young adults with SR-aGVHD. Higher alemtuzumab levels are associated with CR. A real-time dose adjusted alemtuzumab study is needed to further optimize the dose of alemtuzumab in aGVHD.

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“…5,[9][10][11][12][13][14]19,20,[21][22][23][24] However, none of these previous trials were randomized. This phase 3 study was developed to compare outcome between inolimomab and standard therapy.…”

Section: Discussionmentioning

confidence: 99%

A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD

Socié

Vigouroux

Yakoub-Agha

et al. 2017

Blood

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Key Points• In steroid-resistant acute GVHD 1-year survival without changing baseline therapy was not different after inolimomab vs ATG.• Using current care, the expected 1-year survival of these patients lies in the 55% range.Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P 5 .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24. (Blood. 2017129(5):643-649)

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Daclizumab as useful treatment in refractory acute GVHD: a paediatric experience

Cited by 33 publications

References 16 publications

Long‐term follow‐up of children treated with daclizumab for steroid‐refractory gastrointestinal GvHD in a prospective study

Long‐term follow‐up of children treated with daclizumab for steroid‐refractory gastrointestinal GvHD in a prospective study

A Prospective Study of Alemtuzumab as a Second-Line Agent for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation

A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD

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