Contributions
Abstract: EP1753
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Progressive multifocal leukoencepahlopathy (PML) is a major concern when using biotherapies for multiple sclerosis (MS) treatment. PML is frequent with natalizumab (NTZ), considered as rare with fingolimod (FGL). Current guidelines on how and when to switch treatment in patients at high PML risk are expert based. They allowed to minimize PML risk but not to avoid new PML cases. Recent studies highlighted the use of the low level of CD62L (L-selectin) ( < 10%) as a predictive biomarker of further PML development in NTZ-treated MS patients (Schwab et al., 2013; Pignolet et al., 2016).
Objectives: To evaluate and confirm the 10% threshold of CD62L as a PML risk stratification biomarker (PRSB) in NTZ and FGL treated MS patients at high PML risk.
Methods: We are using the Best-MS cohort (NCT01981161), a multicentre, observational prospective study conducted to evaluate CD62L as a PRSB. CD62L was monitored by flowcytometry every 3 months for NTZ and 6 months for FGL on CD4 T cells derived from frozen/thawn PBMC. Patient inclusion criteria included: -a- more than 18 months under NTZ or FGL, positive for JC virus serology with -b- an index value (IV) higher than 0.9 or -c- prior immunossupress. CD62L determination was centralized in only 1 laboratory (Toulouse). We proposed to stop NTZ or FGL only when under 10% of CD62L. A collegial decision on how to switch was performed. All patients signed an informed consent.
Results: Started in 2013 and currently by March 2017, 353 patients have been included with 311 under NTZ and 42 under FGL. None of the FGL treated patients experienced a CD62L < 10%. In the NTZ-treated group, only 3.6 % of the patients experienced a low level of CD62L (< 10 %). All patients have been switched to another drug: mean follow-up before switch = 19.6 months ; 9 % to FGL, 50 % to Rituximab, 35 % to Tecfidera and 6 % to Alemtuzumab).
Currently, no PML case was observed.
Conclusions: So far, in this cohort, no new PML case was observed. Thus, this prospective study is a first confirmation of the interest of CD62L as a PRSB that may be useful in daily clinical practice.
Disclosure:
Dr Pignolet, F Bucciarelli, L Scandella, S Exbrayat, Dr Ciron, Dr Rigal, Dr Robinson, Dr Casez, Dr Montcuquet, Dr Angibaud, Dr Cabrejo, Dr Sablot, Dr Guennoc, Dr Larrieu, Dr Formoso, Dr Elias, Porf Debouverie, Dr Pittion, Dr Rico, Prof Pelletier, Prof Clavelou, Dr Lebrun-Frenay: nothing to disclose
Dr Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme and Novartis.
Prof Brochet has received consultancy fees, speaker fees, research grants (non-personal), or honoraria from Novartis, Biogen-Idec, Merck, Bayer Schering, Roche, Medday, Bayer, Actelion, Teva and Genzyme Sanofi.
Dr Derache has received funding for speakers honoraria from Merck-Serono, Biogen-Idec, Novartis, Teva and Sanofi-Genzyme.
Dr Patry has received honoraria and consulting fees from Novartis and research supports from Biogen and Novartis
Prof. Vukusic has received consultancy fees, speaker fees, research grants (non-personal) or honoraria from Biogen, Geneuro, Genzyme-Sanofi, Medday, Merck-Serono, Novartis, Roche and Teva.
Prof. Brassat has received consulting fees and speaker honoraria from Biogen, Sanofi-Genzyme, Bayer, Novartis, Teva, Merck-Serono, Roche and Medday
Abstract: EP1753
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Progressive multifocal leukoencepahlopathy (PML) is a major concern when using biotherapies for multiple sclerosis (MS) treatment. PML is frequent with natalizumab (NTZ), considered as rare with fingolimod (FGL). Current guidelines on how and when to switch treatment in patients at high PML risk are expert based. They allowed to minimize PML risk but not to avoid new PML cases. Recent studies highlighted the use of the low level of CD62L (L-selectin) ( < 10%) as a predictive biomarker of further PML development in NTZ-treated MS patients (Schwab et al., 2013; Pignolet et al., 2016).
Objectives: To evaluate and confirm the 10% threshold of CD62L as a PML risk stratification biomarker (PRSB) in NTZ and FGL treated MS patients at high PML risk.
Methods: We are using the Best-MS cohort (NCT01981161), a multicentre, observational prospective study conducted to evaluate CD62L as a PRSB. CD62L was monitored by flowcytometry every 3 months for NTZ and 6 months for FGL on CD4 T cells derived from frozen/thawn PBMC. Patient inclusion criteria included: -a- more than 18 months under NTZ or FGL, positive for JC virus serology with -b- an index value (IV) higher than 0.9 or -c- prior immunossupress. CD62L determination was centralized in only 1 laboratory (Toulouse). We proposed to stop NTZ or FGL only when under 10% of CD62L. A collegial decision on how to switch was performed. All patients signed an informed consent.
Results: Started in 2013 and currently by March 2017, 353 patients have been included with 311 under NTZ and 42 under FGL. None of the FGL treated patients experienced a CD62L < 10%. In the NTZ-treated group, only 3.6 % of the patients experienced a low level of CD62L (< 10 %). All patients have been switched to another drug: mean follow-up before switch = 19.6 months ; 9 % to FGL, 50 % to Rituximab, 35 % to Tecfidera and 6 % to Alemtuzumab).
Currently, no PML case was observed.
Conclusions: So far, in this cohort, no new PML case was observed. Thus, this prospective study is a first confirmation of the interest of CD62L as a PRSB that may be useful in daily clinical practice.
Disclosure:
Dr Pignolet, F Bucciarelli, L Scandella, S Exbrayat, Dr Ciron, Dr Rigal, Dr Robinson, Dr Casez, Dr Montcuquet, Dr Angibaud, Dr Cabrejo, Dr Sablot, Dr Guennoc, Dr Larrieu, Dr Formoso, Dr Elias, Porf Debouverie, Dr Pittion, Dr Rico, Prof Pelletier, Prof Clavelou, Dr Lebrun-Frenay: nothing to disclose
Dr Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme and Novartis.
Prof Brochet has received consultancy fees, speaker fees, research grants (non-personal), or honoraria from Novartis, Biogen-Idec, Merck, Bayer Schering, Roche, Medday, Bayer, Actelion, Teva and Genzyme Sanofi.
Dr Derache has received funding for speakers honoraria from Merck-Serono, Biogen-Idec, Novartis, Teva and Sanofi-Genzyme.
Dr Patry has received honoraria and consulting fees from Novartis and research supports from Biogen and Novartis
Prof. Vukusic has received consultancy fees, speaker fees, research grants (non-personal) or honoraria from Biogen, Geneuro, Genzyme-Sanofi, Medday, Merck-Serono, Novartis, Roche and Teva.
Prof. Brassat has received consulting fees and speaker honoraria from Biogen, Sanofi-Genzyme, Bayer, Novartis, Teva, Merck-Serono, Roche and Medday