Contributions
Abstract: P1231
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: The effect of Alemtuzumab (ATZ) in Multiple Sclerosis (MS) relies on the profound depletion of lymphocytes carrying the CD52 surface molecule. While antibodies binding to ATZ are detected in the majority of treated patients, these were so far not shown to affect the lymphocyte depleting effect of the drug. We describe a patient in whom the third treatment cycle with ATZ failed to deplete lymphocytes, and this was shown to be due to neutralizing antibodies.
Case report: a 27 year-old otherwise healthy female was diagnosed with relapsing-remitting MS in 2/2010. After treatment courses with IFNß1b and Fingolimod she received her first and second cycle of ATZ in February 2015 and February 2016, respectively. Apart from moderate typical infusion-related reaction (IAR) this was well tolerated. The time course and extent of peripheral blood leukocyte depletion and repletion were typical of ATZ, e.g. the total lymphocyte count fell from 2.86 G/L pretreatment to 0.09 one month after the first cycle, and 0.81 to 0.25 after the second cycle.
In February 2017 she received her third cycle on the ground of isolated MRI inflammatory activity (no relapses, EDSS 1). During infusion on day one the patient developped tachycardia (120 bpm) dyspnea, palpitation and a transient and limited rash that was compatible with an IAR. Repeat full blood counts in the days, weeks and months after this cycle failed to show the peripheral lymphocyte depletion characteristic of ATZ (0.87 G/L pretreatment and 0.88 at one month).
In an in vitro depletion model we demonstrated that functionally active neutralizing antibodies in the serum of this patient inhibited ATZ binding and lymphocytes depletion.
Three months after her third cycle the patients is clinically stable but MRI shows some new T2 lesions and four new Gad-enhancing lesions. There were no episodes of infectious or autoimmune disease that might potentially affect peripheral blood counts. Steroids were only given on the three days of ATZ infusion.
Conclusions: To our knowledge this is the first demonstration of neutralizing anti-ATZ antibodies that block the binding of this monoclonal antibody to its target and fully abrogate lymphocyte depletion. This finding was paralleled by ongoing inflammatory MRI activity thus supporting the clinical relevance of this phenomenon.
Disclosure:
C. Eggers received speakers fees and honoraria from Sanofi-Genzyme, Teva, Merck-Serono, Biogen-Idec and Novartis.
K. Thomas has nothing to declare
T. Hofer has nothing to declare
M. Egger has nothing to declare
T. Ziemssen received speakers fees and honoraria from Sanofi-Genzyme, Teva, Biogen-Idec and Novartis.
Abstract: P1231
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: The effect of Alemtuzumab (ATZ) in Multiple Sclerosis (MS) relies on the profound depletion of lymphocytes carrying the CD52 surface molecule. While antibodies binding to ATZ are detected in the majority of treated patients, these were so far not shown to affect the lymphocyte depleting effect of the drug. We describe a patient in whom the third treatment cycle with ATZ failed to deplete lymphocytes, and this was shown to be due to neutralizing antibodies.
Case report: a 27 year-old otherwise healthy female was diagnosed with relapsing-remitting MS in 2/2010. After treatment courses with IFNß1b and Fingolimod she received her first and second cycle of ATZ in February 2015 and February 2016, respectively. Apart from moderate typical infusion-related reaction (IAR) this was well tolerated. The time course and extent of peripheral blood leukocyte depletion and repletion were typical of ATZ, e.g. the total lymphocyte count fell from 2.86 G/L pretreatment to 0.09 one month after the first cycle, and 0.81 to 0.25 after the second cycle.
In February 2017 she received her third cycle on the ground of isolated MRI inflammatory activity (no relapses, EDSS 1). During infusion on day one the patient developped tachycardia (120 bpm) dyspnea, palpitation and a transient and limited rash that was compatible with an IAR. Repeat full blood counts in the days, weeks and months after this cycle failed to show the peripheral lymphocyte depletion characteristic of ATZ (0.87 G/L pretreatment and 0.88 at one month).
In an in vitro depletion model we demonstrated that functionally active neutralizing antibodies in the serum of this patient inhibited ATZ binding and lymphocytes depletion.
Three months after her third cycle the patients is clinically stable but MRI shows some new T2 lesions and four new Gad-enhancing lesions. There were no episodes of infectious or autoimmune disease that might potentially affect peripheral blood counts. Steroids were only given on the three days of ATZ infusion.
Conclusions: To our knowledge this is the first demonstration of neutralizing anti-ATZ antibodies that block the binding of this monoclonal antibody to its target and fully abrogate lymphocyte depletion. This finding was paralleled by ongoing inflammatory MRI activity thus supporting the clinical relevance of this phenomenon.
Disclosure:
C. Eggers received speakers fees and honoraria from Sanofi-Genzyme, Teva, Merck-Serono, Biogen-Idec and Novartis.
K. Thomas has nothing to declare
T. Hofer has nothing to declare
M. Egger has nothing to declare
T. Ziemssen received speakers fees and honoraria from Sanofi-Genzyme, Teva, Biogen-Idec and Novartis.