Effect of Extended Interval Dose Natalizumab therapy on CD19+ and CD34+ cell mobilization from bone marrow and JC Viremia. (P5.397)

Objective: Investigate whether extending Natalizumab (NTZ) dosing interval may attenuate CD34+ and CD19+ cell mobilization from bone marrow and JC viremia. 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 postulated to be due in part, to NTZ-induced mobilization of JC virus (JCV) 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. Design/Methods: Blood from RRMS NTZ treated patients was separated using flow cytometry into CD34+and two subpopulations of CD19+ cells, CD19+/CD27+ (memory) and CD19+/IgD+/CD27− (naive) cells. DNA templates were 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 “early” EID NTZ (35 – 36d) and “late” EID NTZ (42–56) were compared to those on standard interval dose (SID) schedule (28 – 34d). Results: 20 EID and 10 SID patients: mean age (range) EID 44.8 (28–70); SID 43 (19–60) years; total NTZ infusions mean (range) EID 46 (14–102) (2–9) SID 41 (16–77) ; days between infusions over the last 12months mean (range) EID 44.8 (35–56) SID 28 (27–29) ; JCV index mean (range) EID 0.58 (0.19–2.82) and SID 0.16 (0.09 – 0.26). Frequency of CD34+ cell mobilization was reduced in patients with “late” vs “early” EID extension (p=0.0017). Conclusions: This ongoing study is evaluating biological effects of EID NTZ dosing that may be pertinent to PML risk. Preliminary data shows reduced CD34+ mobilization with NTZ dosing extended to 42–56 days. Additional patient samples under evaluation will be presented. Disclosure: Dr. Zhovtis Ryerson has received personal compensation for activities with Biogen Idec and Teva as a speaker and advisory board member. Dr. Zhovtis Ryerson has received research support from Biogen Idec. Dr. Monaco has nothing to disclose. Dr. Kister has nothing to disclose. Dr. Zuniga - Estrada has nothing to disclose. Dr. Jacob has nothing to disclose. Dr. Bacon has nothing to disclose. Dr. Jensen has nothing to disclose. Dr. Major has received license payments from the NIH Office of Technology Transfer as well as an ELISA assay technology.