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Carfilzomib for Refractory Antibody Mediated Rejection and Allosensitization in Heart Transplantation
Abstracts S31 6( 3) Carfilzomib for Refractory Antibody Mediated Rejection and Allosensitization in Heart Transplantation L. Sacha ,1 J.J. Teuteberg,2 A. Zeevi,3 C. Bermudez,2 R. Kormos,2 C. Ensor,1 J. McDyer,4 M.A. Shullo.1 1Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA; 2Heart and Vascular Institute, UPMC, Pittsburgh, PA; 3Histopathopathy, University of Pittsburgh, Pittsburgh, PA; 4Medicine, University of Pittsburgh, Pittsburgh, PA. Introduction: Both persistent and de novo donor specific antibodies(DSA) after heart transplant correlate with significantly worse mortality compared to that of patients without DSAs. Recently there is increasing interest in proteasome inhibitors for therapy, given their targeted effect on plasma cells. Carfilzomib is a proteasome inhibitor which, in contrast to bortezomib, irreversibly inhibits activity of the 20S proteasome and results in less neuropathic side effects. This is a case series of two allosensitized patients who received carfilzomib (CFZ); one heart transplant(HTX) candidate and one HTX recipient. Case Report: Patient A is a 54 y/o female with a HVAD as a bridge to HTX, highly sensitized with cPRA of 100% based on IgG HLA-antibodies(Ab) and a 96% cPRA based on C1q testing. IVIG and plasmapheresis(PP) were ineffective; therefore she was treated with one round of CFZ therapy consisting of 6 treatments of PP, CFZ 20 mg/m2 and IVIG. After the first round of therapy, cPRA and anti-HLA Ab strength were mildly reduced and the C1q positive Ab were eradicated. This response was not sustained and not sufficient for HTX listing. A second round of CFZ therapy, successfully reduced her cPRA to 51% by eliminating C1q positive class I HLA-Ab and considering only class II strong HLA-Ab. Ten days later she was successfully transplanted across C1q negative weak class I and II DSA. Patient B is 58 y/o male, 4 years post HTX with a first episode of antibody mediated rejection (AMR) with strong Class II C1q positive DQ8 DSA. He was symptomatic with an EF of 25% and failed to have a sustained respond to steroids, PP, IVIG, and rituximab. After one round of CFZ therapy as defined above, no C1q positive DSA were detected and remains asymptomatic with an EF of 50-55% 5 months later. Summary: For allosensitized HTX candidates or those with AMR, a regimen of, PP, CFZ, and IVIG results in a rapid decline in Ab, as well as a decrease in their ability to activate complement. Further study is warranted on the use of CFZ for these indications.
6( 4) Belatacept as Primary Immunosuppression in a Lung Transplant Recipient P. Ong ,1 L. Mudambi,1 A. Fuentes,2 K. Dawson,2 N. Sinha,3 B. Mankidy,3 S. Scheinin,1 T. Kaleekal,3 S. Jyothula.3 1Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX; 2Department of Pharmacy, Houston Methodist Hospital, Houston, TX; 3JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX. Introduction: Belatacept is a recently-introduced, selective costimulation blocker approved for immunosuppression in renal transplant recipients. This
agent has a potential benefit over standard calcineurin (CNI) based immunosuppression in that it avoids CNI nephrotoxicity. To our knowledge, available literature regarding the use of belatacept in lung transplantation is currently limited to one case study. Case Report: We report on a 64 year old female who underwent bilateral lung transplantation 2 years prior secondary to Idiopathic Pulmonary Fibrosis. Current immunosuppression consisted of tacrolimus, sirolimus and prednisone. The patient presented to the acute care setting with decreased appetite, tiredness, shortness of breath and minimal epistaxis. Empiric antibiotics were initiated and a bronchoscopy showed alveolar hemorrhage. Of note, the patient also presented with acute kidney injury, thrombocytopenia, and confusion/lethargy. A peripheral smear showed the presence of schiztocytes, and a diagnosis of Thrombocytopenic Thrombotic Purpura / Hemolytic Uremic Syndrome (TTP/HUS) was made. She received 5 sessions of therapeutic plasma exchange. At that time, her TTP/HUS was thought to be secondary to tacrolimus - which was discontinued. Sirolimus was also stopped due to the uncertain nature of her alveolar hemorrhage. After extensive deliberation, this patient was started on belatacept every 2 weeks and ciprofloxacin for meningococcal prophylaxis. She could not be placed on cell cycle inhibitors due to leucopenia and existing bone marrow suppression. The patient’s platelet count, mental status and renal function eventually improved with plasma exchange, and she was discharged to a rehabilitation facility. A surveillance bronchoscopy performed 4 weeks after initiating belatacept was negative for acute rejection. Furthermore, donor specific antibodies remained negative at this time. Summary: In summary, we present the case of a lung transplant patient unable to tolerate CNI or mTOR based immunosuppression who is successfully maintained on the costimulatory antagonist belatacept at present. Belatacept may be considered in lung transplant recipients as an immunosuppressive agent of last resort for those unable to tolerate more conventional therapies, and further studies are needed to fully elucidate its utility in this population. 6( 5) Successful Use of Cidofovir and Leflunomide in Lung Transplant Recipient with BK Polyomavirus Encephalitis P. Ong ,1 A. Fuentes,2 K. Dawson,2 N. Sinha,3 B. Mankidy,3 M. Loebe,3 T. Kaleekal,3 S. Jyothula.3 1Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX; 2Department of Pharmacy, Houston Methodist Hospital, Houston, TX; 3JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX. Introduction: The importance of polyomavirus BK as cause of nephropathy in renal allograft recipients is well documented, and it is also a known cause of urothelial disease causing hematuria after bone marrow transplantation. We report a rare case of BK polyoma virus encephalitis in a lung transplant patient, and its successful treatment with cidofovir, leflunomide and reduced immunosuppression. Case Report: We present the case of a 58-year-old African American female with a history of bilateral lung transplantation 3 years ago for COPD. The patient was recently diagnosed with Bronchiolitis Obliterans Syndrome and treated with rabbit antithymocyte globulin (rATG). Maintenance immunosuppression included tacrolimus, sirolimus and low dose prednisone. Approximately 1 month after receiving rATG, the patient was admitted for acute renal failure and hyperkalemia requiring dialysis. During this hospitalization, her mental status deteriorated, with a waxing and waning course, and delirium was initially suspected. MRI of the brain showed moderate signal change in the peri-ventricular white matter and on the pons. A lumbar puncture was performed showing elevated protein, normal glucose, and an elevated opening pressure. Further viral studies revealed a BK Virus PCR of 750 copies/ul. Her plasma BK virus PCR was negative. Given her mental status, MRI results, and CSF PCR findings, the patient was initiated on Cidofovir 2mg/kg IV every 2 weeks and Leflunomide 40 mg daily. This regimen was extrapolated from protocols in patients who developed renal allograft BK virus nephropathy. After a prolonged ICU stay, the patient transitioned to acute care and acute rehabilitation where her weakness and mental status improved. After one month of treatment with cidofovir, leflunamide and reduced immunosuppression, she has improved with physical therapy and is no longer bedridden. A repeat lumbar puncture after 4 weeks of treatment showed clearance of the virus from the CSF. Summary: In summary, BK virus encephalitis may be a potential cause of altered mental status and leathery in severely immunosuppressed lung transplant recipients. Treatment with Cidofovir and Leflunomide, along with reduced immunosuppression, can be considered in this setting.
6( 4) Belatacept as Primary Immunosuppression in a Lung Transplant Recipient P. Ong ,1 L. Mudambi,1 A. Fuentes,2 K. Dawson,2 N. Sinha,3 B. Mankidy,3 S. Scheinin,1 T. Kaleekal,3 S. Jyothula.3 1Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX; 2Department of Pharmacy, Houston Methodist Hospital, Houston, TX; 3JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX. Introduction: Belatacept is a recently-introduced, selective costimulation blocker approved for immunosuppression in renal transplant recipients. This
agent has a potential benefit over standard calcineurin (CNI) based immunosuppression in that it avoids CNI nephrotoxicity. To our knowledge, available literature regarding the use of belatacept in lung transplantation is currently limited to one case study. Case Report: We report on a 64 year old female who underwent bilateral lung transplantation 2 years prior secondary to Idiopathic Pulmonary Fibrosis. Current immunosuppression consisted of tacrolimus, sirolimus and prednisone. The patient presented to the acute care setting with decreased appetite, tiredness, shortness of breath and minimal epistaxis. Empiric antibiotics were initiated and a bronchoscopy showed alveolar hemorrhage. Of note, the patient also presented with acute kidney injury, thrombocytopenia, and confusion/lethargy. A peripheral smear showed the presence of schiztocytes, and a diagnosis of Thrombocytopenic Thrombotic Purpura / Hemolytic Uremic Syndrome (TTP/HUS) was made. She received 5 sessions of therapeutic plasma exchange. At that time, her TTP/HUS was thought to be secondary to tacrolimus - which was discontinued. Sirolimus was also stopped due to the uncertain nature of her alveolar hemorrhage. After extensive deliberation, this patient was started on belatacept every 2 weeks and ciprofloxacin for meningococcal prophylaxis. She could not be placed on cell cycle inhibitors due to leucopenia and existing bone marrow suppression. The patient’s platelet count, mental status and renal function eventually improved with plasma exchange, and she was discharged to a rehabilitation facility. A surveillance bronchoscopy performed 4 weeks after initiating belatacept was negative for acute rejection. Furthermore, donor specific antibodies remained negative at this time. Summary: In summary, we present the case of a lung transplant patient unable to tolerate CNI or mTOR based immunosuppression who is successfully maintained on the costimulatory antagonist belatacept at present. Belatacept may be considered in lung transplant recipients as an immunosuppressive agent of last resort for those unable to tolerate more conventional therapies, and further studies are needed to fully elucidate its utility in this population. 6( 5) Successful Use of Cidofovir and Leflunomide in Lung Transplant Recipient with BK Polyomavirus Encephalitis P. Ong ,1 A. Fuentes,2 K. Dawson,2 N. Sinha,3 B. Mankidy,3 M. Loebe,3 T. Kaleekal,3 S. Jyothula.3 1Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX; 2Department of Pharmacy, Houston Methodist Hospital, Houston, TX; 3JC Walter Jr Transplant Center, Houston Methodist Hospital, Houston, TX. Introduction: The importance of polyomavirus BK as cause of nephropathy in renal allograft recipients is well documented, and it is also a known cause of urothelial disease causing hematuria after bone marrow transplantation. We report a rare case of BK polyoma virus encephalitis in a lung transplant patient, and its successful treatment with cidofovir, leflunomide and reduced immunosuppression. Case Report: We present the case of a 58-year-old African American female with a history of bilateral lung transplantation 3 years ago for COPD. The patient was recently diagnosed with Bronchiolitis Obliterans Syndrome and treated with rabbit antithymocyte globulin (rATG). Maintenance immunosuppression included tacrolimus, sirolimus and low dose prednisone. Approximately 1 month after receiving rATG, the patient was admitted for acute renal failure and hyperkalemia requiring dialysis. During this hospitalization, her mental status deteriorated, with a waxing and waning course, and delirium was initially suspected. MRI of the brain showed moderate signal change in the peri-ventricular white matter and on the pons. A lumbar puncture was performed showing elevated protein, normal glucose, and an elevated opening pressure. Further viral studies revealed a BK Virus PCR of 750 copies/ul. Her plasma BK virus PCR was negative. Given her mental status, MRI results, and CSF PCR findings, the patient was initiated on Cidofovir 2mg/kg IV every 2 weeks and Leflunomide 40 mg daily. This regimen was extrapolated from protocols in patients who developed renal allograft BK virus nephropathy. After a prolonged ICU stay, the patient transitioned to acute care and acute rehabilitation where her weakness and mental status improved. After one month of treatment with cidofovir, leflunamide and reduced immunosuppression, she has improved with physical therapy and is no longer bedridden. A repeat lumbar puncture after 4 weeks of treatment showed clearance of the virus from the CSF. Summary: In summary, BK virus encephalitis may be a potential cause of altered mental status and leathery in severely immunosuppressed lung transplant recipients. Treatment with Cidofovir and Leflunomide, along with reduced immunosuppression, can be considered in this setting.