Contributions
Abstract: P711
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Objective: Investigate when extending Natalizumab (NTZ) dosing interval may attenuate CD34+ cell mobilization from bone marrow.
Background: NTZ extended interval dosing (EID) (35 - 58 days) is an approach being explored to reduce the risk of PML without compromising effectiveness of drug. PML susceptibility has been associated, in part, to NTZ-induced mobilization of JC virus from the bone marrow into peripheral circulation via CD 19+ and CD34+ cells. Less frequent NTZ dosing may reduce mobilization of these cells, thereby decreasing risk of passage of JCV infected cells into the CNS.
Methods: Blood from RRMS NTZ treated patients was separated using flow cytometry into CD34+, CD19+, and CD3+ subsets. DNA templates prepared using quantitative PCR for JCV DNA identification. Plasma was tested for anti-JCV antibodies by ELISA (NINDS) and compared to commercial assay (Focus). Patients on EID NTZ (35 - 58d) were compared to those on standard interval dose (SID) schedule (28 - 34d).
Results: 20 EID and 7 SID patients: mean age (range) EID 45 (28-70); SID 43 (19-59) years ; EID 50% SID 57% female; mean of MS diagnosis (range) EID 14.1 (3-30) SID 9.8 (1-26) years; duration of NTZ treatment mean (range) EID 5.3 (2-9) SID 3.7 (1-7) years; mean (range) duration on EID 28 (14-64) months; JCV index mean (range) EID 0.58 (0.19 -2.82) and in SID 0.16 (0.09 - 0.26). Extent of CD34+ cell mobilization was similar in both groups. 1/20 EID patients and 1/7 SID patients are viremic with JCV. SID patient was seronegative (antibody titer, 640)(NINDS);JCV index of 0.12 (Focus). EID patient was seropositive (antibody titer 2560) (NINDS); JCV index 0.22 (Focus).
Conclusion: This ongoing study is evaluating biological effects of EID NTZ dosing that may be pertinent to PML risk. Preliminary data does not show reduced CD34+ mobilization with EID NTZ schedule. Additional patient samples from time points further removed from previous NTZ dosing should be evaluated.
Disclosure: Lana Zhovtis Ryerson has received research support from Biogen Idec. She has received compensation for advisory board and speaker activities from Biogen Idec and Teva.
Maria Monaco-Kushner has nothing to disclose.
Ilya Kister has served on scientific advisory board for Biogen Idec and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen-Idec, Serono, and Novartis.
Guadalupe Estrada-Zuniga has nothing to disclose.
April Jacob has nothing to disclose.
Eugene Major reports personal fees from PML Consortium, Takeda/Millennium Pharma, Glaxo Smith Klein, Genentech Roche, and Sanofi Genzyme.
Abstract: P711
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Objective: Investigate when extending Natalizumab (NTZ) dosing interval may attenuate CD34+ cell mobilization from bone marrow.
Background: NTZ extended interval dosing (EID) (35 - 58 days) is an approach being explored to reduce the risk of PML without compromising effectiveness of drug. PML susceptibility has been associated, in part, to NTZ-induced mobilization of JC virus from the bone marrow into peripheral circulation via CD 19+ and CD34+ cells. Less frequent NTZ dosing may reduce mobilization of these cells, thereby decreasing risk of passage of JCV infected cells into the CNS.
Methods: Blood from RRMS NTZ treated patients was separated using flow cytometry into CD34+, CD19+, and CD3+ subsets. DNA templates prepared using quantitative PCR for JCV DNA identification. Plasma was tested for anti-JCV antibodies by ELISA (NINDS) and compared to commercial assay (Focus). Patients on EID NTZ (35 - 58d) were compared to those on standard interval dose (SID) schedule (28 - 34d).
Results: 20 EID and 7 SID patients: mean age (range) EID 45 (28-70); SID 43 (19-59) years ; EID 50% SID 57% female; mean of MS diagnosis (range) EID 14.1 (3-30) SID 9.8 (1-26) years; duration of NTZ treatment mean (range) EID 5.3 (2-9) SID 3.7 (1-7) years; mean (range) duration on EID 28 (14-64) months; JCV index mean (range) EID 0.58 (0.19 -2.82) and in SID 0.16 (0.09 - 0.26). Extent of CD34+ cell mobilization was similar in both groups. 1/20 EID patients and 1/7 SID patients are viremic with JCV. SID patient was seronegative (antibody titer, 640)(NINDS);JCV index of 0.12 (Focus). EID patient was seropositive (antibody titer 2560) (NINDS); JCV index 0.22 (Focus).
Conclusion: This ongoing study is evaluating biological effects of EID NTZ dosing that may be pertinent to PML risk. Preliminary data does not show reduced CD34+ mobilization with EID NTZ schedule. Additional patient samples from time points further removed from previous NTZ dosing should be evaluated.
Disclosure: Lana Zhovtis Ryerson has received research support from Biogen Idec. She has received compensation for advisory board and speaker activities from Biogen Idec and Teva.
Maria Monaco-Kushner has nothing to disclose.
Ilya Kister has served on scientific advisory board for Biogen Idec and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen-Idec, Serono, and Novartis.
Guadalupe Estrada-Zuniga has nothing to disclose.
April Jacob has nothing to disclose.
Eugene Major reports personal fees from PML Consortium, Takeda/Millennium Pharma, Glaxo Smith Klein, Genentech Roche, and Sanofi Genzyme.