Abstract Details

Title B Cells, T Cells and Inflammatory CSF Biomarkers in Primary Progressive MS and Relapsing MS in the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Trial

Topic Multiple Sclerosis

Presentation(s) S40 - Multiple Sclerosis: Clinical Trials (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Background

OCR, an anti-CD20 molecule, reduces progression in MS. Less is known about biomarkers and mechanisms of anti-CD20 action in PPMS than in RMS. Presence of T1 gadolinium–enhancing lesions has been associated with higher baseline cerebrospinal fluid (CSF) NfL and serum NfL (sNfL) in PPMS and RMS and significant sNfL reductions in PPMS (ORATORIO trial, n=347; p<0.001).

Objective

To assess longitudinal changes in B cells, T cells, neurofilament light (NfL) and soluble inflammatory markers in patients with primary progressive (PPMS) and relapsing (RMS) multiple sclerosis following ocrelizumab (OCR) treatment.

Design/Methods

Twenty-eight patients with PPMS in OBOE received 600-mg OCR infusions every 24 weeks. CSF was collected at baseline and 52 weeks. Blood was collected at baseline and 6 postdose time points. Samples were assessed for NfL (Quanterix Advantage), CXCL13 and CCL19 (immunoassay) and CSF B and T cells (flow cytometry). Data were compared with previously reported RMS data.

Results

Baseline CSF B cells, T cells and CCL19 levels were indistinguishable between patients with PPMS and RMS, while CSF NfL (p=0.012) and CXCL13 (p=0.020) were decreased in patients with PPMS. PPMS CSF B cells (n=15; median percent change, −100 [IQR −100, −91.4]; p<0.001) and T cells (n=17; −63.69 [IQR −80.5, −12.9]; p=0.051) were reduced at 52 weeks post-treatment. Neither CSF NfL nor sNfL were decreased at 52 weeks overall (n=28; IQR −51.1, 51.6 and IQR −30.1, 22.5, respectively); however, NfL trended lower in 7 patients with PPMS with baseline T1 gadolinium–enhancing lesions vs those without. CSF CXCL13 levels were reduced in patients with PPMS following OCR treatment but did not achieve significance (n=28; IQR −59.1, 0; p=0.084).

Conclusions

Baseline CSF B cells, T cells and inflammatory biomarkers were similar in PPMS and RMS. In PPMS, similar to RMS, CSF B and T cells and CXCL13 were reduced following OCR treatment.

Authors/Disclosures
Amit Bar-Or, MD, FRCPC (University of Pennsylvania) PRESENTER	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Jeffrey L. Bennett, MD, PhD, FAAN (University of Colorado School of Medicine)	Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immpact Bio. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beigene. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MIAC. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CorEvitas. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Vindico. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Touch IME. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Efficient LLC. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Pavich. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Marie Bush. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Marks Gray. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Knight, Nicastro, MacKay. The institution of Dr. Bennett has received research support from Alexion. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
H.-Christian C. von Büdingen, MD, FAAN (F. Hoffmann-La Roche Ltd)	Dr. Von Buedingen has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd.. Dr. Von Buedingen has received stock or an ownership interest from F. Hoffmann-La Roche Ltd.
Robert L. Carruthers, MD	Dr. Carruthers has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Carruthers has received personal compensation in the range of $0-$499 for serving as a Consultant for Roche and Genentech. The institution of Dr. Carruthers has received research support from Roche and Genentech .
Keith R. Edwards, MD, FAAN (MS Center of Northeastern New York)	No disclosure on file
Robert J. Fallis, MD (Vanderbilt University Medical Center)	No disclosure on file
Damian Fiore	No disclosure on file
Jeffrey M. Gelfand, MD, MAS, FAAN (University of California, San Francisco)	Dr. Gelfand has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ventyx Bio. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities.
Paul S. Giacomini, MD (Montreal Neurological Institute)	Dr. Giacomini has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Innodem Neurosciences. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for F. Hoffmann- La Roche. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Giacomini has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Giacomini has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Giacomini has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffmann-La Roche. Dr. Giacomini has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Giacomini has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for F. Hoffman-La Roche. Dr. Giacomini has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. Dr. Giacomini has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi.
Benjamin M. Greenberg, MD, FAAN (UT Southwestern Medical Center)	Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Greenberg has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Clene. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Greenberg has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Siegel Rare Neuroimmune Association. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Husch Blackwell. Dr. Greenberg has stock in GenrAb. Dr. Greenberg has stock in Clene. The institution of Dr. Greenberg has received research support from Anokion. The institution of Dr. Greenberg has received research support from Regeneron. Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Greenberg has received publishing royalties from a publication relating to health care.
David A. Hafler, MD, FAAN (Yale University School of Medicine, Dept of Neurology)	Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genetech. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Hafler has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Joint Commission International.
Erin Longbrake, MD, PhD, FAAN (Yale University)	Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Longbrake has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ACTRIMS. Dr. Longbrake has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Longbrake has received research support from Genentech. The institution of Dr. Longbrake has received research support from Race to Erase MS. The institution of Dr. Longbrake has received research support from NINDS K23. The institution of Dr. Longbrake has received research support from Robert Patterson Leet Trust. The institution of Dr. Longbrake has received research support from Biogen. The institution of Dr. Longbrake has received research support from National MS Society. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Programmatic Review with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with National Institute of Health .
	No disclosure on file
Carolina Ionete, MD (UMass Memorial)	Dr. Ionete has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Ionete has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Zenas. Dr. Ionete has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Ionete has received research support from Genetech. The institution of Dr. Ionete has received research support from NIH.
Ulrike Kaunzner, MD (Weill-Cornell)	Dr. Kaunzner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Kaunzner has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medlearning.
Christopher Lock, MD, MBBS, PhD (Stanford University)	Dr. Lock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Lock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Lock has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Turning Point Litigation. Dr. Lock has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Goodell, DeVries, Leech & Dann, LLP. Dr. Lock has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for McQuaide Blasko Attorneys at Law. Dr. Lock has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for BENNETT BIGELOW & LEEDOM P.S. .
Xiaoye Ma	Xiaoye Ma has received personal compensation for serving as an employee of Genentech.
Bruno C. Musch, MD	No disclosure on file
Gabriel Pardo, MD, FAAN (Oklahoma Medical Research Foundation)	Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche Genentech. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen . Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Pardo has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche Genentech. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Pardo has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for TG Therapeutics. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Horizon Therapeutics. Dr. Pardo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals.
Jinglan Pei	Jinglan Pei has nothing to disclose.
Fredrik L. Piehl, MD, PhD (Neuroimmunology Unit, Dept Clinical Neuroscience, Karolinska Institutet)	Dr. Piehl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parexel/Chugai. The institution of Dr. Piehl has received research support from UCB. The institution of Dr. Piehl has received research support from Merck KGaA. Dr. Piehl has received personal compensation in the range of $10,000-$49,999 for serving as a member scientific advisory board with Swedish Medical products Agency.
	No disclosure on file
Tjalf Ziemssen, MD, FAAN (University Clinic Dresden)	Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. The institution of Dr. Ziemssen has received research support from Biogen. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from Celgene.
Ann Herman	Ann Herman has received personal compensation for serving as an employee of Genentech, Inc. Ann Herman has received stock or an ownership interest from F. Hoffman-La Roche Ltd.
Christopher Harp	Christopher Harp has received personal compensation for serving as an employee of Genentech. Christopher Harp has received stock or an ownership interest from Genentech, Inc..
Anne H. Cross, MD, FAAN (Washington University School of Medicine)	Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech / F. Hoffman la Roche. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb . Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Cross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Consortium of MS Centers. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Cross has received research support from Genentech. Dr. Cross has received intellectual property interests from a discovery or technology relating to health care.

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