BORTEZOMIB IN THE MANAGEMENT OF ACUTE TTP ? DIFFICULTY IN MONITORING PROGRESS
(Abstract release date: 05/21/15)
EHA Library. Low R. 06/12/15; 103049; PB1964
Disclosure(s): University of Liverpool
Ryan Low
Contributions
Contributions
Abstract
Abstract: PB1964
Type: Publication Only
Background
Thrombotic Thrombocytopenic Purpura (TTP) is a rare but life threatening condition that has an untreated mortality of 90%. It is characterised by the presence of autoantibodies against the von Willebrand factor cleaving enzyme ADAMTS13.(1) Therapeutic plasma exchange (PLEX) remains the mainstay treatment – adjuvant immunosuppressant therapy with rituximab is also required in some patients.(2)
Aims
We report the case of an acute acquired TTP that did not respond to PLEX or rituximab however rapidly responded to the proteasome inhibitor, commonly used in multiple myeloma, bortezomib.
Methods
The case is of a 59 year old gentleman who presented with vomiting, progressive dizziness and double vision. Acute TTP was confirmed and the patient was commenced on once daily PLEX to which he had an inadequate response. He was subsequently initiated on twice daily PLEX and prescribed four doses of rituximab. Again only a partial response was observed, so based on case report data, a course of bortezomib was trialed alongside the twice daily PLEX.
Results
A relatively quick recovery in platelet count was observed, and although difficult to interpret the ADAMTS13 inhibitor titre and ADAMTS13 activity normalised. The patient was discharged 57 days post diagnosis and has remained stable since.
Summary
This case supports the use of bortezomib as an adjuvant therapy in the management of acute TTP where PLEX and rituximab have been ineffective. Flow cytometry conducted on this patient’s bone marrow post-rituximab revealed a normal CD19 count supporting the failure of rituximab in this case. One potential reason that is important to consider, is that effect of twice daily plasma exchange on the pharmacokinetics of rituximab, evidence suggests peak plasma concentrations are difficult to achieve during PLEX.(3) The PLEX also made it difficult to monitor progress with bortezomib, as both ADAMST13 and its inhibitor titre were unreliable representations of disease activity.
Keyword(s): Bortezomib, Thrombotic thrombocytopenic purpura (TTP)
Session topic: Publication Only
Type: Publication Only
Background
Thrombotic Thrombocytopenic Purpura (TTP) is a rare but life threatening condition that has an untreated mortality of 90%. It is characterised by the presence of autoantibodies against the von Willebrand factor cleaving enzyme ADAMTS13.(1) Therapeutic plasma exchange (PLEX) remains the mainstay treatment – adjuvant immunosuppressant therapy with rituximab is also required in some patients.(2)
Aims
We report the case of an acute acquired TTP that did not respond to PLEX or rituximab however rapidly responded to the proteasome inhibitor, commonly used in multiple myeloma, bortezomib.
Methods
The case is of a 59 year old gentleman who presented with vomiting, progressive dizziness and double vision. Acute TTP was confirmed and the patient was commenced on once daily PLEX to which he had an inadequate response. He was subsequently initiated on twice daily PLEX and prescribed four doses of rituximab. Again only a partial response was observed, so based on case report data, a course of bortezomib was trialed alongside the twice daily PLEX.
Results
A relatively quick recovery in platelet count was observed, and although difficult to interpret the ADAMTS13 inhibitor titre and ADAMTS13 activity normalised. The patient was discharged 57 days post diagnosis and has remained stable since.
Summary
This case supports the use of bortezomib as an adjuvant therapy in the management of acute TTP where PLEX and rituximab have been ineffective. Flow cytometry conducted on this patient’s bone marrow post-rituximab revealed a normal CD19 count supporting the failure of rituximab in this case. One potential reason that is important to consider, is that effect of twice daily plasma exchange on the pharmacokinetics of rituximab, evidence suggests peak plasma concentrations are difficult to achieve during PLEX.(3) The PLEX also made it difficult to monitor progress with bortezomib, as both ADAMST13 and its inhibitor titre were unreliable representations of disease activity.
Keyword(s): Bortezomib, Thrombotic thrombocytopenic purpura (TTP)
Session topic: Publication Only
Abstract: PB1964
Type: Publication Only
Background
Thrombotic Thrombocytopenic Purpura (TTP) is a rare but life threatening condition that has an untreated mortality of 90%. It is characterised by the presence of autoantibodies against the von Willebrand factor cleaving enzyme ADAMTS13.(1) Therapeutic plasma exchange (PLEX) remains the mainstay treatment – adjuvant immunosuppressant therapy with rituximab is also required in some patients.(2)
Aims
We report the case of an acute acquired TTP that did not respond to PLEX or rituximab however rapidly responded to the proteasome inhibitor, commonly used in multiple myeloma, bortezomib.
Methods
The case is of a 59 year old gentleman who presented with vomiting, progressive dizziness and double vision. Acute TTP was confirmed and the patient was commenced on once daily PLEX to which he had an inadequate response. He was subsequently initiated on twice daily PLEX and prescribed four doses of rituximab. Again only a partial response was observed, so based on case report data, a course of bortezomib was trialed alongside the twice daily PLEX.
Results
A relatively quick recovery in platelet count was observed, and although difficult to interpret the ADAMTS13 inhibitor titre and ADAMTS13 activity normalised. The patient was discharged 57 days post diagnosis and has remained stable since.
Summary
This case supports the use of bortezomib as an adjuvant therapy in the management of acute TTP where PLEX and rituximab have been ineffective. Flow cytometry conducted on this patient’s bone marrow post-rituximab revealed a normal CD19 count supporting the failure of rituximab in this case. One potential reason that is important to consider, is that effect of twice daily plasma exchange on the pharmacokinetics of rituximab, evidence suggests peak plasma concentrations are difficult to achieve during PLEX.(3) The PLEX also made it difficult to monitor progress with bortezomib, as both ADAMST13 and its inhibitor titre were unreliable representations of disease activity.
Keyword(s): Bortezomib, Thrombotic thrombocytopenic purpura (TTP)
Session topic: Publication Only
Type: Publication Only
Background
Thrombotic Thrombocytopenic Purpura (TTP) is a rare but life threatening condition that has an untreated mortality of 90%. It is characterised by the presence of autoantibodies against the von Willebrand factor cleaving enzyme ADAMTS13.(1) Therapeutic plasma exchange (PLEX) remains the mainstay treatment – adjuvant immunosuppressant therapy with rituximab is also required in some patients.(2)
Aims
We report the case of an acute acquired TTP that did not respond to PLEX or rituximab however rapidly responded to the proteasome inhibitor, commonly used in multiple myeloma, bortezomib.
Methods
The case is of a 59 year old gentleman who presented with vomiting, progressive dizziness and double vision. Acute TTP was confirmed and the patient was commenced on once daily PLEX to which he had an inadequate response. He was subsequently initiated on twice daily PLEX and prescribed four doses of rituximab. Again only a partial response was observed, so based on case report data, a course of bortezomib was trialed alongside the twice daily PLEX.
Results
A relatively quick recovery in platelet count was observed, and although difficult to interpret the ADAMTS13 inhibitor titre and ADAMTS13 activity normalised. The patient was discharged 57 days post diagnosis and has remained stable since.
Summary
This case supports the use of bortezomib as an adjuvant therapy in the management of acute TTP where PLEX and rituximab have been ineffective. Flow cytometry conducted on this patient’s bone marrow post-rituximab revealed a normal CD19 count supporting the failure of rituximab in this case. One potential reason that is important to consider, is that effect of twice daily plasma exchange on the pharmacokinetics of rituximab, evidence suggests peak plasma concentrations are difficult to achieve during PLEX.(3) The PLEX also made it difficult to monitor progress with bortezomib, as both ADAMST13 and its inhibitor titre were unreliable representations of disease activity.
Keyword(s): Bortezomib, Thrombotic thrombocytopenic purpura (TTP)
Session topic: Publication Only
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