Abstract: Characterization of Peripheral Immune Cell Dynamics and Repopulation Patterns in the First 12 Months of Cladribine Tablets Treatment: Magnify-MS Study (2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers)

DMT33
Characterization of Peripheral Immune Cell Dynamics and Repopulation Patterns in the First 12 Months of Cladribine Tablets Treatment: Magnify-MS Study

Tuesday, October 26, 2021

Exhibit Hall (Rosen Shingle Creek)

Heinz Wiendl, MD , Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany

Klaus Schmierer, MD, PhD , The Blizard Institute (Neuroscience), Queen Mary University of London, London, United Kingdom

Suzanne Hodgkinson, MD , Immune Tolerance Group, Ingham Institute for Applied Medical Research, UNSW Medicine, Liverpool, Australia

Tobias Derfuss, MD , Neurology Clinic and Policlinic and Research Center for Clinical Neuroimmunology and Neuroscience, Departments of Medicine and Biomedicine, University Hospital and University of Basel, Basel, Switzerland

Andrew Chan, MD , Ambulantes Neurozentrum, Inselspital, Bern, Switzerland

Finn Sellebjerg, MD , Department of Neurology, Multiple sclerosis & Neuroimmunology Division, University of Texas Southwestern Medical Center, Dallas, TX

Anat Achiron, MD, PhD , Sheba Medical Center, Ramat Gan, Israel

Xavier Montalban, MD, PhD , Division of Neurology, St Michael’s Hospital, University of Toronto, Toronto, ON, Canada

Alexandre Prat, MD , Department of Neurosciences, Université de Montréal, Montréal, QC, Canada

Nicola De Stefano, MD, PhD , University of Siena, Siena, Italy

Frederik Barkhof, MD, PhD , Institutes of Neurology and Healthcare Engineering, University College London, London, United Kingdom, Department of Radiology, VU University Medical Center, Amsterdam, Netherlands

Letizia Leocani, MD , Ospedale San Raffaele, Milano, Italy

Patrick Vermersch, PhD , University of Lille, Inserm U1172 LilNCog, CHU Lille, FHU Imminent, Lille, France

Anita Chudecka, MA , Cytel, Inc., Cambridge, MA

Sanjeev Roy, MD , Merck KGaA, Darmstadt, Germany, Aubonne, Switzerland

Ursula Boschert, PhD , Merck KGaA, Darmstadt, Germany, Eysins, Switzerland

Background:

The action of cladribine tablets (CladT) on immune cells may be key for both onset and durability of its effect in people with multiple sclerosis (MS).

Objectives:

To report on peripheral immune cell subset dynamics and immunoglobulin levels in the first 12 months of CladT therapy.

Methods:

Longitudinal evaluation of peripheral blood immune cells in patients receiving CladT in a sub-study of MAGNIFY-MS (NCT03364036). Absolute cell counts and percent change from baseline were assessed for adaptive immune cell subtypes and immunoglobulins. Immunophenotyping was completed at baseline and months 1, 2, 3, 6, and 12.

Results:

Full analysis set: 57 patients (median age 37 years; 61% female; ≥2 relapses in previous year, 70%). Effector and regulatory B cells were reduced from Month 1 and showed a subtype-specific repopulation pattern. Change from baseline for CD19+ B cells: Month 1, -77%; Month 2, -90%; Month 12, -35%. Memory B cells: Month 1, -74%; Month 3, -93%; Month 12,-87%. Plasmablasts: Month 1, -28%; Month 3, -78%; Month 12, -51%. Regulatory B cells (CD19+, CD24bright, and CD38bright): Month 1, -45%; Month 3, +176%; Month 6, +171%; Month 12, +50%. Naïve/transitional B cells: Month 1, -79%/-61%; Month 3, -69%/+35%; Month 12, +35%/+23%. Decrease in T cell subsets was moderate and slower, nadir occurring between 3 and 6 months. T-helper 17 CD4+ and terminally differentiated effector memory CD8+ T cell counts reached nadir at Month 3 (-35% and -25%, respectively). No clinically meaningful change in serum IgG or IgM was observed over 12 months.

Conclusions:

Assessment of lymphocyte dynamics following CladT over 1 year demonstrates that effects occur from Month 1, and are sustained in several immune cell subpopulations. CladT exerts a pronounced effect on memory B cells, while immunoglobulin levels are unaffected over 12 months. Results suggest early onset of CladT action, underpinned by MAGNIFY-MS MRI results, may be mediated through this specific pattern of sustained decrease and reconstitution of B and T cell subtypes in a highly active MS population.

DMT33 Characterization of Peripheral Immune Cell Dynamics and Repopulation Patterns in the First 12 Months of Cladribine Tablets Treatment: Magnify-MS Study

DMT33
Characterization of Peripheral Immune Cell Dynamics and Repopulation Patterns in the First 12 Months of Cladribine Tablets Treatment: Magnify-MS Study