ETANERCEPT FOR STEROID-REFRACTORY ACUTE GRAFT-VERSUS-HOST DISEASE: A SINGLE CENTER EXPERIENCE
(Abstract release date: 05/19/16)
EHA Library. de Jong N. 06/09/16; 133081; E1532
Dr. Niels de Jong
Contributions
Contributions
Abstract
Abstract: E1532
Type: Eposter Presentation
Background
Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation (alloSCT). High dose systemic glucocorticosteroids (steroids) are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40 to 50 percent of patients. Currently, there is no standard second-line treatment for steroid-refractory aGVHD (SR-aGVHD). Etanercept is a recombinant human tumor necrosis receptor fusion protein which inhibits the biological activity of tumor necrosis factor alpha (TNFα) involved in the pathophysiology of aGVHD. Studies that have investigated the use of anti-TNFα as primary as well as secondary treatment in aGVHD have shown promising results.1,2
Aims
Here we report the results of a retrospective analysis of patients with SR-aGVHD treated with etanercept in our center.
Methods
We studied the outcome of sixteen patients following alloSCT with SR-aGVHD, who gave consent for second-line treatment with the TNFα inhibitor etanercept (Enbrel, Pfizer) between January 2009 and April 2013. Etanercept was added to the initiated first-line treatment with high dose steroids combined with cyclosporine A (CsA) or mycophenolate mofetil (MMF) and administered subcutaneously twice weekly at a dose of 25 mg for a maximum of eight weeks.
Results
aGVHD developed at a median of 61 days post-transplantation. In all cases it concerned grade 3 aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after the initiation of first-line treatment. First-line treatment consisted of 2 mg/kg steroids combined either with CsA in fourteen patients or MMF in two patients and was continued during treatment with etanercept until a sustained response was achieved. The overall response rate was 50%, including a complete response (CR) in three patients (18.8%) and a partial response (PR) in five patients (31,3%). Responses were reached after a median duration of treatment of 9 days (range 5-40 days). Despite a promising initial response rate, five out of eight responding patients lost their response. One CR patient developed progressive GVHD after treatment with etanercept had to be discontinued because of the development of post-transplant EBV-related lymphoproliferative disorder. In addition, four PR patients lost their response during treatment with etanercept. Clinically significant infectious complications occurred in thirteen patients, including bacterial septicemia, viral infections and invasive pulmonary aspergillosis. Eventually, all sixteen patients died at a median of 57 days (range 1 –267 days) after initiation of etanercept. Death was caused by progressive GVHD in seven cases (43.8%), opportunistic infections in six cases (37.5%), cardiac death in two cases (12.5%) and relapse of the original malignancy in one case (6%).
Conclusion
Second-line treatment of SR-aGVHD of the gut with the TNFα inhibitor etanercept did not meet the promising results reported by Busca et al.2 While etanercept showed a promising initial response rate of 50% in our patients, survival was very poor, which was mainly due to opportunistic infections in the context of ongoing or progressive GVHD, even in patients, who initially responded. References:1. Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ, et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008;111(4):2470-5.2. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82(1):45-52.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, Etanercept, Graft-versus-host disease (GVHD)
Type: Eposter Presentation
Background
Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation (alloSCT). High dose systemic glucocorticosteroids (steroids) are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40 to 50 percent of patients. Currently, there is no standard second-line treatment for steroid-refractory aGVHD (SR-aGVHD). Etanercept is a recombinant human tumor necrosis receptor fusion protein which inhibits the biological activity of tumor necrosis factor alpha (TNFα) involved in the pathophysiology of aGVHD. Studies that have investigated the use of anti-TNFα as primary as well as secondary treatment in aGVHD have shown promising results.1,2
Aims
Here we report the results of a retrospective analysis of patients with SR-aGVHD treated with etanercept in our center.
Methods
We studied the outcome of sixteen patients following alloSCT with SR-aGVHD, who gave consent for second-line treatment with the TNFα inhibitor etanercept (Enbrel, Pfizer) between January 2009 and April 2013. Etanercept was added to the initiated first-line treatment with high dose steroids combined with cyclosporine A (CsA) or mycophenolate mofetil (MMF) and administered subcutaneously twice weekly at a dose of 25 mg for a maximum of eight weeks.
Results
aGVHD developed at a median of 61 days post-transplantation. In all cases it concerned grade 3 aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after the initiation of first-line treatment. First-line treatment consisted of 2 mg/kg steroids combined either with CsA in fourteen patients or MMF in two patients and was continued during treatment with etanercept until a sustained response was achieved. The overall response rate was 50%, including a complete response (CR) in three patients (18.8%) and a partial response (PR) in five patients (31,3%). Responses were reached after a median duration of treatment of 9 days (range 5-40 days). Despite a promising initial response rate, five out of eight responding patients lost their response. One CR patient developed progressive GVHD after treatment with etanercept had to be discontinued because of the development of post-transplant EBV-related lymphoproliferative disorder. In addition, four PR patients lost their response during treatment with etanercept. Clinically significant infectious complications occurred in thirteen patients, including bacterial septicemia, viral infections and invasive pulmonary aspergillosis. Eventually, all sixteen patients died at a median of 57 days (range 1 –267 days) after initiation of etanercept. Death was caused by progressive GVHD in seven cases (43.8%), opportunistic infections in six cases (37.5%), cardiac death in two cases (12.5%) and relapse of the original malignancy in one case (6%).
Conclusion
Second-line treatment of SR-aGVHD of the gut with the TNFα inhibitor etanercept did not meet the promising results reported by Busca et al.2 While etanercept showed a promising initial response rate of 50% in our patients, survival was very poor, which was mainly due to opportunistic infections in the context of ongoing or progressive GVHD, even in patients, who initially responded. References:1. Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ, et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008;111(4):2470-5.2. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82(1):45-52.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, Etanercept, Graft-versus-host disease (GVHD)
Abstract: E1532
Type: Eposter Presentation
Background
Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation (alloSCT). High dose systemic glucocorticosteroids (steroids) are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40 to 50 percent of patients. Currently, there is no standard second-line treatment for steroid-refractory aGVHD (SR-aGVHD). Etanercept is a recombinant human tumor necrosis receptor fusion protein which inhibits the biological activity of tumor necrosis factor alpha (TNFα) involved in the pathophysiology of aGVHD. Studies that have investigated the use of anti-TNFα as primary as well as secondary treatment in aGVHD have shown promising results.1,2
Aims
Here we report the results of a retrospective analysis of patients with SR-aGVHD treated with etanercept in our center.
Methods
We studied the outcome of sixteen patients following alloSCT with SR-aGVHD, who gave consent for second-line treatment with the TNFα inhibitor etanercept (Enbrel, Pfizer) between January 2009 and April 2013. Etanercept was added to the initiated first-line treatment with high dose steroids combined with cyclosporine A (CsA) or mycophenolate mofetil (MMF) and administered subcutaneously twice weekly at a dose of 25 mg for a maximum of eight weeks.
Results
aGVHD developed at a median of 61 days post-transplantation. In all cases it concerned grade 3 aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after the initiation of first-line treatment. First-line treatment consisted of 2 mg/kg steroids combined either with CsA in fourteen patients or MMF in two patients and was continued during treatment with etanercept until a sustained response was achieved. The overall response rate was 50%, including a complete response (CR) in three patients (18.8%) and a partial response (PR) in five patients (31,3%). Responses were reached after a median duration of treatment of 9 days (range 5-40 days). Despite a promising initial response rate, five out of eight responding patients lost their response. One CR patient developed progressive GVHD after treatment with etanercept had to be discontinued because of the development of post-transplant EBV-related lymphoproliferative disorder. In addition, four PR patients lost their response during treatment with etanercept. Clinically significant infectious complications occurred in thirteen patients, including bacterial septicemia, viral infections and invasive pulmonary aspergillosis. Eventually, all sixteen patients died at a median of 57 days (range 1 –267 days) after initiation of etanercept. Death was caused by progressive GVHD in seven cases (43.8%), opportunistic infections in six cases (37.5%), cardiac death in two cases (12.5%) and relapse of the original malignancy in one case (6%).
Conclusion
Second-line treatment of SR-aGVHD of the gut with the TNFα inhibitor etanercept did not meet the promising results reported by Busca et al.2 While etanercept showed a promising initial response rate of 50% in our patients, survival was very poor, which was mainly due to opportunistic infections in the context of ongoing or progressive GVHD, even in patients, who initially responded. References:1. Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ, et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008;111(4):2470-5.2. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82(1):45-52.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, Etanercept, Graft-versus-host disease (GVHD)
Type: Eposter Presentation
Background
Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation (alloSCT). High dose systemic glucocorticosteroids (steroids) are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40 to 50 percent of patients. Currently, there is no standard second-line treatment for steroid-refractory aGVHD (SR-aGVHD). Etanercept is a recombinant human tumor necrosis receptor fusion protein which inhibits the biological activity of tumor necrosis factor alpha (TNFα) involved in the pathophysiology of aGVHD. Studies that have investigated the use of anti-TNFα as primary as well as secondary treatment in aGVHD have shown promising results.1,2
Aims
Here we report the results of a retrospective analysis of patients with SR-aGVHD treated with etanercept in our center.
Methods
We studied the outcome of sixteen patients following alloSCT with SR-aGVHD, who gave consent for second-line treatment with the TNFα inhibitor etanercept (Enbrel, Pfizer) between January 2009 and April 2013. Etanercept was added to the initiated first-line treatment with high dose steroids combined with cyclosporine A (CsA) or mycophenolate mofetil (MMF) and administered subcutaneously twice weekly at a dose of 25 mg for a maximum of eight weeks.
Results
aGVHD developed at a median of 61 days post-transplantation. In all cases it concerned grade 3 aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after the initiation of first-line treatment. First-line treatment consisted of 2 mg/kg steroids combined either with CsA in fourteen patients or MMF in two patients and was continued during treatment with etanercept until a sustained response was achieved. The overall response rate was 50%, including a complete response (CR) in three patients (18.8%) and a partial response (PR) in five patients (31,3%). Responses were reached after a median duration of treatment of 9 days (range 5-40 days). Despite a promising initial response rate, five out of eight responding patients lost their response. One CR patient developed progressive GVHD after treatment with etanercept had to be discontinued because of the development of post-transplant EBV-related lymphoproliferative disorder. In addition, four PR patients lost their response during treatment with etanercept. Clinically significant infectious complications occurred in thirteen patients, including bacterial septicemia, viral infections and invasive pulmonary aspergillosis. Eventually, all sixteen patients died at a median of 57 days (range 1 –267 days) after initiation of etanercept. Death was caused by progressive GVHD in seven cases (43.8%), opportunistic infections in six cases (37.5%), cardiac death in two cases (12.5%) and relapse of the original malignancy in one case (6%).
Conclusion
Second-line treatment of SR-aGVHD of the gut with the TNFα inhibitor etanercept did not meet the promising results reported by Busca et al.2 While etanercept showed a promising initial response rate of 50% in our patients, survival was very poor, which was mainly due to opportunistic infections in the context of ongoing or progressive GVHD, even in patients, who initially responded. References:1. Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ, et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008;111(4):2470-5.2. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82(1):45-52.
Session topic: E-poster
Keyword(s): Allogeneic hematopoietic stem cell transplant, Etanercept, Graft-versus-host disease (GVHD)
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