COMPLETE RESOLUTION OF EXTENSIVE CHRONIC GRAFT-VERSUS-HOST DISEASE WITH IBRUTINIB
(Abstract release date: 05/21/15)
EHA Library. Obi G. 06/12/15; 102804; PB2051
Disclosure(s): CAGT Baylor College of Medicine and Houston Methodist HospitalHematology Oncology
Gloria Obi
Contributions
Contributions
Abstract
Abstract: PB2051
Type: Publication Only
Background
Chronic graft versus host disease (cGvHD) is mediated donor T cells. The role of B cells in the pathogenesis of cGvHD is increasingly recognized. Two murine studies have explored the role of ibrutinib in cGVHD-like syndromes, one in which there is T cell driven sclerodermatous cGvHD and a second in which there is Ab driven multiorgan system cGvHD that includes bronchiolitis obliterans.
Aims
We herein document a complete response of extensive chronic graft-versus-host disease (cGvHD) to a Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib.
Methods
Following approval from Institute Review Board, patient disease and transplant related variables were studies in a single patient who received Ibrutinib for post- allogeneic transplant relapse of mantle cell lymphoma (MCL). NIH criteria for cGvHD diagnosis and staging were followed for disease assessment.
Results
A 41 years old female with primary refractory MCL underwent mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in December 2011 (ablative conditioning with CY/TBI and alemtuzumab, graft=6.6x 106/kg CD-34+ cells, tacrolimus alone for GVHD prevention). Following engraftment on day 11, she developed grade III acute GvHD involving the skin and gut on day 17 of transplantation that persisted beyond 100 days post-transplant. Her cGvHD was treated with steroids, but remained active and extensive. Despite persistent cGvHD and 100% donor chimerism she relapsed in July 2012. Treatment with radiation, bendamustine and rituximab failed. By December 2013, the patient had extensive cGvHD manifesting as scleromatous skin thickening, oral ulcers and sclerosis of the buccal mucosa, ocular dryness and diarrhea, and was started on ibrutinib1 560 mg once daily for relapsed MCL. After 8 weeks of therapy, cGvHD had begun to improve. Oral steroids were reduced and ultimately stopped after 26 weeks of ibrutinib; after 30 weeks treatment all cGvHD manifestations resolved completely. A complete remission for MCL was documented at 8 weeks of ibrutinib initiation. Currently she continues to be on 560 mg daily ibrutinib without cGvHD exacerbation or MCL relapse for 22 weeks and 52 weeks, respectively.
Summary
Our report provides the evidence for BTK inhibition led complete cGvHD resolution and supports exploration of its role in future clinical trials.
Keyword(s): Chronic graft-versus-host, Mantle cell lymphoma
Session topic: Publication Only
Type: Publication Only
Background
Chronic graft versus host disease (cGvHD) is mediated donor T cells. The role of B cells in the pathogenesis of cGvHD is increasingly recognized. Two murine studies have explored the role of ibrutinib in cGVHD-like syndromes, one in which there is T cell driven sclerodermatous cGvHD and a second in which there is Ab driven multiorgan system cGvHD that includes bronchiolitis obliterans.
Aims
We herein document a complete response of extensive chronic graft-versus-host disease (cGvHD) to a Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib.
Methods
Following approval from Institute Review Board, patient disease and transplant related variables were studies in a single patient who received Ibrutinib for post- allogeneic transplant relapse of mantle cell lymphoma (MCL). NIH criteria for cGvHD diagnosis and staging were followed for disease assessment.
Results
A 41 years old female with primary refractory MCL underwent mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in December 2011 (ablative conditioning with CY/TBI and alemtuzumab, graft=6.6x 106/kg CD-34+ cells, tacrolimus alone for GVHD prevention). Following engraftment on day 11, she developed grade III acute GvHD involving the skin and gut on day 17 of transplantation that persisted beyond 100 days post-transplant. Her cGvHD was treated with steroids, but remained active and extensive. Despite persistent cGvHD and 100% donor chimerism she relapsed in July 2012. Treatment with radiation, bendamustine and rituximab failed. By December 2013, the patient had extensive cGvHD manifesting as scleromatous skin thickening, oral ulcers and sclerosis of the buccal mucosa, ocular dryness and diarrhea, and was started on ibrutinib1 560 mg once daily for relapsed MCL. After 8 weeks of therapy, cGvHD had begun to improve. Oral steroids were reduced and ultimately stopped after 26 weeks of ibrutinib; after 30 weeks treatment all cGvHD manifestations resolved completely. A complete remission for MCL was documented at 8 weeks of ibrutinib initiation. Currently she continues to be on 560 mg daily ibrutinib without cGvHD exacerbation or MCL relapse for 22 weeks and 52 weeks, respectively.
Summary
Our report provides the evidence for BTK inhibition led complete cGvHD resolution and supports exploration of its role in future clinical trials.
Keyword(s): Chronic graft-versus-host, Mantle cell lymphoma
Session topic: Publication Only
Abstract: PB2051
Type: Publication Only
Background
Chronic graft versus host disease (cGvHD) is mediated donor T cells. The role of B cells in the pathogenesis of cGvHD is increasingly recognized. Two murine studies have explored the role of ibrutinib in cGVHD-like syndromes, one in which there is T cell driven sclerodermatous cGvHD and a second in which there is Ab driven multiorgan system cGvHD that includes bronchiolitis obliterans.
Aims
We herein document a complete response of extensive chronic graft-versus-host disease (cGvHD) to a Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib.
Methods
Following approval from Institute Review Board, patient disease and transplant related variables were studies in a single patient who received Ibrutinib for post- allogeneic transplant relapse of mantle cell lymphoma (MCL). NIH criteria for cGvHD diagnosis and staging were followed for disease assessment.
Results
A 41 years old female with primary refractory MCL underwent mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in December 2011 (ablative conditioning with CY/TBI and alemtuzumab, graft=6.6x 106/kg CD-34+ cells, tacrolimus alone for GVHD prevention). Following engraftment on day 11, she developed grade III acute GvHD involving the skin and gut on day 17 of transplantation that persisted beyond 100 days post-transplant. Her cGvHD was treated with steroids, but remained active and extensive. Despite persistent cGvHD and 100% donor chimerism she relapsed in July 2012. Treatment with radiation, bendamustine and rituximab failed. By December 2013, the patient had extensive cGvHD manifesting as scleromatous skin thickening, oral ulcers and sclerosis of the buccal mucosa, ocular dryness and diarrhea, and was started on ibrutinib1 560 mg once daily for relapsed MCL. After 8 weeks of therapy, cGvHD had begun to improve. Oral steroids were reduced and ultimately stopped after 26 weeks of ibrutinib; after 30 weeks treatment all cGvHD manifestations resolved completely. A complete remission for MCL was documented at 8 weeks of ibrutinib initiation. Currently she continues to be on 560 mg daily ibrutinib without cGvHD exacerbation or MCL relapse for 22 weeks and 52 weeks, respectively.
Summary
Our report provides the evidence for BTK inhibition led complete cGvHD resolution and supports exploration of its role in future clinical trials.
Keyword(s): Chronic graft-versus-host, Mantle cell lymphoma
Session topic: Publication Only
Type: Publication Only
Background
Chronic graft versus host disease (cGvHD) is mediated donor T cells. The role of B cells in the pathogenesis of cGvHD is increasingly recognized. Two murine studies have explored the role of ibrutinib in cGVHD-like syndromes, one in which there is T cell driven sclerodermatous cGvHD and a second in which there is Ab driven multiorgan system cGvHD that includes bronchiolitis obliterans.
Aims
We herein document a complete response of extensive chronic graft-versus-host disease (cGvHD) to a Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib.
Methods
Following approval from Institute Review Board, patient disease and transplant related variables were studies in a single patient who received Ibrutinib for post- allogeneic transplant relapse of mantle cell lymphoma (MCL). NIH criteria for cGvHD diagnosis and staging were followed for disease assessment.
Results
A 41 years old female with primary refractory MCL underwent mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in December 2011 (ablative conditioning with CY/TBI and alemtuzumab, graft=6.6x 106/kg CD-34+ cells, tacrolimus alone for GVHD prevention). Following engraftment on day 11, she developed grade III acute GvHD involving the skin and gut on day 17 of transplantation that persisted beyond 100 days post-transplant. Her cGvHD was treated with steroids, but remained active and extensive. Despite persistent cGvHD and 100% donor chimerism she relapsed in July 2012. Treatment with radiation, bendamustine and rituximab failed. By December 2013, the patient had extensive cGvHD manifesting as scleromatous skin thickening, oral ulcers and sclerosis of the buccal mucosa, ocular dryness and diarrhea, and was started on ibrutinib1 560 mg once daily for relapsed MCL. After 8 weeks of therapy, cGvHD had begun to improve. Oral steroids were reduced and ultimately stopped after 26 weeks of ibrutinib; after 30 weeks treatment all cGvHD manifestations resolved completely. A complete remission for MCL was documented at 8 weeks of ibrutinib initiation. Currently she continues to be on 560 mg daily ibrutinib without cGvHD exacerbation or MCL relapse for 22 weeks and 52 weeks, respectively.
Summary
Our report provides the evidence for BTK inhibition led complete cGvHD resolution and supports exploration of its role in future clinical trials.
Keyword(s): Chronic graft-versus-host, Mantle cell lymphoma
Session topic: Publication Only
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