IS C-REACTIVE PROTEIN A RELIABLE SURROGATE MARKER FOR INFECTION TO HELP FACILITATE DISCHARGE IN PATIENTS ON IBRUTINIB? (A SINGLE CENTRE EXPERIENCE)
(Abstract release date: 05/19/16)
EHA Library. Sparksman D. 06/09/16; 134702; PB1802
Dr. David Sparksman
Contributions
Contributions
Abstract
Abstract: PB1802
Type: Publication Only
Background
C-Reactive Protein (CRP) is an acute phase protein made by the Liver in response to interleukin-6 (IL-6). It is produced from cells including macrophages, T and B Cells in response to inflammation. It is a poor marker of sepsis at day zero, rising at 4-6 hours and peaking at 36 hours. Ibrutinib is a covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK is an essential part of the B-cell receptor signalling pathway. It mediates both the microenvironment system and promotes survival and proliferation of B-cells. Anecdotally, since Ibrutinib’s introduction as a treatment for Chronic lymphocytic Leukaemia (CLL), Mantle Cell Lymphoma (MCL) and Waldenstrom’s Macroglobulinaemia (WM) we have noticed some patients admitted with confirmed infections whose CRP response was lower than expected.
Aims
To analyse the correlation between CRP and confirmed infections in all patients on Ibrutinib at a small single centre in the UK.
Methods
We retrospectively reviewed the notes of all 46 patients who had been started on Ibrutinib since its approval, and collected data including sequential CRP’s (significant if > 60 mg/L) for all episodes requiring admission with confirmed infection, defined as a positive culture result (blood, sputum, skin swab, mid stream urine), or imaging changes consistent with an infection (as reported by Radiology).
Results
Of the 46 patients (29 CLL, 17 MCL) to have received treatment, only 16 (10 CLL, 6 MCL) were admitted to hospital with infection. 5 of these 16 patients had multiple admissions resulting in 25 admission episodes. Of these 25 episodes only 15 met the criteria for confirmed infection. On analysis of the data, the mean length of stay was 10.1 days with a mean admission CRP of 73 mg/L which rose to 85 mg/L at 48 hours. The majority of the episodes (10/15, 67%) appear to have had an appropriate CRP response in the first 48 hours. Of interest one of these 10 was diagnosed with Listeria monocytogenes on multiple blood cultures, the admission CRP (58 mg/L) did not rise significantly at 24 hours (68 mg/L) and fell thereafter. The patient never mounted an appropriate response for the clinical picture and by the time she died at day 15 her CRP was 3 mg/L. Of the 5 remaining episodes who’s CRP remained low in the first 48 hours (mean CRP 25 mg/L) 4 had imaging and symptoms consistent with a chest infection and 1 was blood culture positive for Pseudomonas aeruginosa sepsis (mean length of admission in this group 10.2 days). The data shows 33% of admission episodes with confirmed infection did not have a significant rise in CRP in the first 48 hours.
Conclusion
In clinical trials Ibrutinib has shown excellent results and the number of patients taking it stand to rise considerably over the coming years. Our single centre study is relatively small and did not obtain enough data to say whether CRP is a reliable surrogate marker for infection in this group. However the 5 cases with low CRP and to a certain extent the 6th (Listeria monocytogenes case) mentioned above raise the possibility that Ibrutinib could have an effect on CRP that has yet to be identified. The proposed possible mechanism would be IL-6 reduction. For this reason we have changed departmental policy, stopping Ibrutinib on admission, relying on clinical picture in the first 48 hours before re-checking CRP to assess response to treatment and therefore likelihood for discharge. Possible areas for further investigation include a multicentre study looking for correlation, comparing alternative inflammatory markers and evaluating IL-6 release in patients with infections on Ibrutinib.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Mantle cell lymphoma
Type: Publication Only
Background
C-Reactive Protein (CRP) is an acute phase protein made by the Liver in response to interleukin-6 (IL-6). It is produced from cells including macrophages, T and B Cells in response to inflammation. It is a poor marker of sepsis at day zero, rising at 4-6 hours and peaking at 36 hours. Ibrutinib is a covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK is an essential part of the B-cell receptor signalling pathway. It mediates both the microenvironment system and promotes survival and proliferation of B-cells. Anecdotally, since Ibrutinib’s introduction as a treatment for Chronic lymphocytic Leukaemia (CLL), Mantle Cell Lymphoma (MCL) and Waldenstrom’s Macroglobulinaemia (WM) we have noticed some patients admitted with confirmed infections whose CRP response was lower than expected.
Aims
To analyse the correlation between CRP and confirmed infections in all patients on Ibrutinib at a small single centre in the UK.
Methods
We retrospectively reviewed the notes of all 46 patients who had been started on Ibrutinib since its approval, and collected data including sequential CRP’s (significant if > 60 mg/L) for all episodes requiring admission with confirmed infection, defined as a positive culture result (blood, sputum, skin swab, mid stream urine), or imaging changes consistent with an infection (as reported by Radiology).
Results
Of the 46 patients (29 CLL, 17 MCL) to have received treatment, only 16 (10 CLL, 6 MCL) were admitted to hospital with infection. 5 of these 16 patients had multiple admissions resulting in 25 admission episodes. Of these 25 episodes only 15 met the criteria for confirmed infection. On analysis of the data, the mean length of stay was 10.1 days with a mean admission CRP of 73 mg/L which rose to 85 mg/L at 48 hours. The majority of the episodes (10/15, 67%) appear to have had an appropriate CRP response in the first 48 hours. Of interest one of these 10 was diagnosed with Listeria monocytogenes on multiple blood cultures, the admission CRP (58 mg/L) did not rise significantly at 24 hours (68 mg/L) and fell thereafter. The patient never mounted an appropriate response for the clinical picture and by the time she died at day 15 her CRP was 3 mg/L. Of the 5 remaining episodes who’s CRP remained low in the first 48 hours (mean CRP 25 mg/L) 4 had imaging and symptoms consistent with a chest infection and 1 was blood culture positive for Pseudomonas aeruginosa sepsis (mean length of admission in this group 10.2 days). The data shows 33% of admission episodes with confirmed infection did not have a significant rise in CRP in the first 48 hours.
Conclusion
In clinical trials Ibrutinib has shown excellent results and the number of patients taking it stand to rise considerably over the coming years. Our single centre study is relatively small and did not obtain enough data to say whether CRP is a reliable surrogate marker for infection in this group. However the 5 cases with low CRP and to a certain extent the 6th (Listeria monocytogenes case) mentioned above raise the possibility that Ibrutinib could have an effect on CRP that has yet to be identified. The proposed possible mechanism would be IL-6 reduction. For this reason we have changed departmental policy, stopping Ibrutinib on admission, relying on clinical picture in the first 48 hours before re-checking CRP to assess response to treatment and therefore likelihood for discharge. Possible areas for further investigation include a multicentre study looking for correlation, comparing alternative inflammatory markers and evaluating IL-6 release in patients with infections on Ibrutinib.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Mantle cell lymphoma
Abstract: PB1802
Type: Publication Only
Background
C-Reactive Protein (CRP) is an acute phase protein made by the Liver in response to interleukin-6 (IL-6). It is produced from cells including macrophages, T and B Cells in response to inflammation. It is a poor marker of sepsis at day zero, rising at 4-6 hours and peaking at 36 hours. Ibrutinib is a covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK is an essential part of the B-cell receptor signalling pathway. It mediates both the microenvironment system and promotes survival and proliferation of B-cells. Anecdotally, since Ibrutinib’s introduction as a treatment for Chronic lymphocytic Leukaemia (CLL), Mantle Cell Lymphoma (MCL) and Waldenstrom’s Macroglobulinaemia (WM) we have noticed some patients admitted with confirmed infections whose CRP response was lower than expected.
Aims
To analyse the correlation between CRP and confirmed infections in all patients on Ibrutinib at a small single centre in the UK.
Methods
We retrospectively reviewed the notes of all 46 patients who had been started on Ibrutinib since its approval, and collected data including sequential CRP’s (significant if > 60 mg/L) for all episodes requiring admission with confirmed infection, defined as a positive culture result (blood, sputum, skin swab, mid stream urine), or imaging changes consistent with an infection (as reported by Radiology).
Results
Of the 46 patients (29 CLL, 17 MCL) to have received treatment, only 16 (10 CLL, 6 MCL) were admitted to hospital with infection. 5 of these 16 patients had multiple admissions resulting in 25 admission episodes. Of these 25 episodes only 15 met the criteria for confirmed infection. On analysis of the data, the mean length of stay was 10.1 days with a mean admission CRP of 73 mg/L which rose to 85 mg/L at 48 hours. The majority of the episodes (10/15, 67%) appear to have had an appropriate CRP response in the first 48 hours. Of interest one of these 10 was diagnosed with Listeria monocytogenes on multiple blood cultures, the admission CRP (58 mg/L) did not rise significantly at 24 hours (68 mg/L) and fell thereafter. The patient never mounted an appropriate response for the clinical picture and by the time she died at day 15 her CRP was 3 mg/L. Of the 5 remaining episodes who’s CRP remained low in the first 48 hours (mean CRP 25 mg/L) 4 had imaging and symptoms consistent with a chest infection and 1 was blood culture positive for Pseudomonas aeruginosa sepsis (mean length of admission in this group 10.2 days). The data shows 33% of admission episodes with confirmed infection did not have a significant rise in CRP in the first 48 hours.
Conclusion
In clinical trials Ibrutinib has shown excellent results and the number of patients taking it stand to rise considerably over the coming years. Our single centre study is relatively small and did not obtain enough data to say whether CRP is a reliable surrogate marker for infection in this group. However the 5 cases with low CRP and to a certain extent the 6th (Listeria monocytogenes case) mentioned above raise the possibility that Ibrutinib could have an effect on CRP that has yet to be identified. The proposed possible mechanism would be IL-6 reduction. For this reason we have changed departmental policy, stopping Ibrutinib on admission, relying on clinical picture in the first 48 hours before re-checking CRP to assess response to treatment and therefore likelihood for discharge. Possible areas for further investigation include a multicentre study looking for correlation, comparing alternative inflammatory markers and evaluating IL-6 release in patients with infections on Ibrutinib.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Mantle cell lymphoma
Type: Publication Only
Background
C-Reactive Protein (CRP) is an acute phase protein made by the Liver in response to interleukin-6 (IL-6). It is produced from cells including macrophages, T and B Cells in response to inflammation. It is a poor marker of sepsis at day zero, rising at 4-6 hours and peaking at 36 hours. Ibrutinib is a covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK is an essential part of the B-cell receptor signalling pathway. It mediates both the microenvironment system and promotes survival and proliferation of B-cells. Anecdotally, since Ibrutinib’s introduction as a treatment for Chronic lymphocytic Leukaemia (CLL), Mantle Cell Lymphoma (MCL) and Waldenstrom’s Macroglobulinaemia (WM) we have noticed some patients admitted with confirmed infections whose CRP response was lower than expected.
Aims
To analyse the correlation between CRP and confirmed infections in all patients on Ibrutinib at a small single centre in the UK.
Methods
We retrospectively reviewed the notes of all 46 patients who had been started on Ibrutinib since its approval, and collected data including sequential CRP’s (significant if > 60 mg/L) for all episodes requiring admission with confirmed infection, defined as a positive culture result (blood, sputum, skin swab, mid stream urine), or imaging changes consistent with an infection (as reported by Radiology).
Results
Of the 46 patients (29 CLL, 17 MCL) to have received treatment, only 16 (10 CLL, 6 MCL) were admitted to hospital with infection. 5 of these 16 patients had multiple admissions resulting in 25 admission episodes. Of these 25 episodes only 15 met the criteria for confirmed infection. On analysis of the data, the mean length of stay was 10.1 days with a mean admission CRP of 73 mg/L which rose to 85 mg/L at 48 hours. The majority of the episodes (10/15, 67%) appear to have had an appropriate CRP response in the first 48 hours. Of interest one of these 10 was diagnosed with Listeria monocytogenes on multiple blood cultures, the admission CRP (58 mg/L) did not rise significantly at 24 hours (68 mg/L) and fell thereafter. The patient never mounted an appropriate response for the clinical picture and by the time she died at day 15 her CRP was 3 mg/L. Of the 5 remaining episodes who’s CRP remained low in the first 48 hours (mean CRP 25 mg/L) 4 had imaging and symptoms consistent with a chest infection and 1 was blood culture positive for Pseudomonas aeruginosa sepsis (mean length of admission in this group 10.2 days). The data shows 33% of admission episodes with confirmed infection did not have a significant rise in CRP in the first 48 hours.
Conclusion
In clinical trials Ibrutinib has shown excellent results and the number of patients taking it stand to rise considerably over the coming years. Our single centre study is relatively small and did not obtain enough data to say whether CRP is a reliable surrogate marker for infection in this group. However the 5 cases with low CRP and to a certain extent the 6th (Listeria monocytogenes case) mentioned above raise the possibility that Ibrutinib could have an effect on CRP that has yet to be identified. The proposed possible mechanism would be IL-6 reduction. For this reason we have changed departmental policy, stopping Ibrutinib on admission, relying on clinical picture in the first 48 hours before re-checking CRP to assess response to treatment and therefore likelihood for discharge. Possible areas for further investigation include a multicentre study looking for correlation, comparing alternative inflammatory markers and evaluating IL-6 release in patients with infections on Ibrutinib.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Mantle cell lymphoma
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