Contributions
Abstract: EP1565
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Objective: To characterize infusion related reactions (IRRs) in patients with relapsing forms of multiple sclerosis (MS) before and after their first ocrelizumab (OCR) dose following the discontinuation of rituximab (RTX) by comparing associations with B-cell reconstitution and changes in cytokine profiles.
Background: RTX is an anti-CD20 medication that is often used off-label for the treatment of MS. Many of these patients switched to OCR with approval of this new anti-CD20 medication in March 2017. IRRs are common with RTX and have been associated with B-cell reconstitution. Here we examine some of the factors associated with IRRs in patients switching from RTX to OCR.
Methods: Patients at the Rocky Mountain MS Center at the University of Colorado with relapsing forms of MS (n=200) with ≥2 RTX doses were split evenly into 2 cohorts: 1) a comparator arm that continued 2 standard of care doses of RTX, 2) a switch arm (SWT) that transitioned to OCR and received doses on Days 1, 15, and Week 24. For the first 60 SWT patients, plasma samples collected before and after Day 1 and Day 15 infusions, were analyzed using a V-PLEX Human Cytokine 44-Plex kit, using a mesoscale SECTOR Imager 2400. B-cell reconstitution was assessed at OCR Day 1. IRRs were evaluated using the National Cancer Institute's Common Terminology for Adverse Events Scale. SAS was used to perform paired sample T-tests.
Results: Of the first 60 SWT patients, 39 (65%) were female, the mean age was 44.47 (+/-11.4 SD), had MS for 11.49 years (+/-7.8 SD) and had a median EDSS of 3 (2.0-4.3 IQR). They received OCR 235.5 (+/-62.6 SD) days after their last RTX infusion and had received 4.2 courses of RTX. Of these patients, 7 had an IRR on Day 1, of which 1 was grade 1 and 6 were grade 2. (28/58) patients had begun to reconstitute their peripheral B-cells. Seventeen of the 45 cytokines examined significantly changed pre and post OCR infusion on Day 1. Cytokine changes were similar between Day 1 and Day 15, with smaller changes seen at Day 15. Larger changes were observed at Day 1 in patients with B-cell reconstitution. In patients with IRRs, IL-16 (76.6 pg/mL, p=0.019) and IL-27 (359.7 pg/mL, p=0.008) increased significantly, while Eotaxin (-48.6 pg/mL, p=0.032) decreased.
Conclusions: Cytokines changed significantly following OCR infusions. Changes were generally smaller in B-cell depleted patients and on Day 15 infusions. Eotaxin, IL-16, and IL-27 differed in patients who experienced IRRs.
Disclosure: Ian Shelton has nothing to disclose. Nassim Zanganeh has nothing to disclose. Sean Selva has nothing to disclose. Stefan H Sillau has nothing to disclose. Kavita V Nair has consulted and/or received research support from Astellas, Genentech, Novartis, and Biogen; consulting for Astellas and Genentech. Timothy Vollmer has received compensation for activities such as advisory boards, lectures and consultancy with Academic CME; Alcimed; Anthem Blue Cross; Genentech/Roche; Biogen IDEC; Novartis; CellGene; Epigene; Rocky Mountain MS Center;GLG Consulting; Ohio Health; TG Therapeutics; Topaz Therapeutics; Deleara Lawyers; Teva Neuroscience He received research support from Teva Neuroscience; NIH/NINDS; Rocky Mountain MS Center; Actelion; Roche/Genentech; UT Southwestern and TG Therapeutics, Inc. Enrique Alvarez has consulted for Biogen, Genzyme, Genentech, Teva, and Novartis; and received research funding from Rocky Mountain MS Center, Biogen, Novartis, Acorda, and Alkermes.
Abstract: EP1565
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Objective: To characterize infusion related reactions (IRRs) in patients with relapsing forms of multiple sclerosis (MS) before and after their first ocrelizumab (OCR) dose following the discontinuation of rituximab (RTX) by comparing associations with B-cell reconstitution and changes in cytokine profiles.
Background: RTX is an anti-CD20 medication that is often used off-label for the treatment of MS. Many of these patients switched to OCR with approval of this new anti-CD20 medication in March 2017. IRRs are common with RTX and have been associated with B-cell reconstitution. Here we examine some of the factors associated with IRRs in patients switching from RTX to OCR.
Methods: Patients at the Rocky Mountain MS Center at the University of Colorado with relapsing forms of MS (n=200) with ≥2 RTX doses were split evenly into 2 cohorts: 1) a comparator arm that continued 2 standard of care doses of RTX, 2) a switch arm (SWT) that transitioned to OCR and received doses on Days 1, 15, and Week 24. For the first 60 SWT patients, plasma samples collected before and after Day 1 and Day 15 infusions, were analyzed using a V-PLEX Human Cytokine 44-Plex kit, using a mesoscale SECTOR Imager 2400. B-cell reconstitution was assessed at OCR Day 1. IRRs were evaluated using the National Cancer Institute's Common Terminology for Adverse Events Scale. SAS was used to perform paired sample T-tests.
Results: Of the first 60 SWT patients, 39 (65%) were female, the mean age was 44.47 (+/-11.4 SD), had MS for 11.49 years (+/-7.8 SD) and had a median EDSS of 3 (2.0-4.3 IQR). They received OCR 235.5 (+/-62.6 SD) days after their last RTX infusion and had received 4.2 courses of RTX. Of these patients, 7 had an IRR on Day 1, of which 1 was grade 1 and 6 were grade 2. (28/58) patients had begun to reconstitute their peripheral B-cells. Seventeen of the 45 cytokines examined significantly changed pre and post OCR infusion on Day 1. Cytokine changes were similar between Day 1 and Day 15, with smaller changes seen at Day 15. Larger changes were observed at Day 1 in patients with B-cell reconstitution. In patients with IRRs, IL-16 (76.6 pg/mL, p=0.019) and IL-27 (359.7 pg/mL, p=0.008) increased significantly, while Eotaxin (-48.6 pg/mL, p=0.032) decreased.
Conclusions: Cytokines changed significantly following OCR infusions. Changes were generally smaller in B-cell depleted patients and on Day 15 infusions. Eotaxin, IL-16, and IL-27 differed in patients who experienced IRRs.
Disclosure: Ian Shelton has nothing to disclose. Nassim Zanganeh has nothing to disclose. Sean Selva has nothing to disclose. Stefan H Sillau has nothing to disclose. Kavita V Nair has consulted and/or received research support from Astellas, Genentech, Novartis, and Biogen; consulting for Astellas and Genentech. Timothy Vollmer has received compensation for activities such as advisory boards, lectures and consultancy with Academic CME; Alcimed; Anthem Blue Cross; Genentech/Roche; Biogen IDEC; Novartis; CellGene; Epigene; Rocky Mountain MS Center;GLG Consulting; Ohio Health; TG Therapeutics; Topaz Therapeutics; Deleara Lawyers; Teva Neuroscience He received research support from Teva Neuroscience; NIH/NINDS; Rocky Mountain MS Center; Actelion; Roche/Genentech; UT Southwestern and TG Therapeutics, Inc. Enrique Alvarez has consulted for Biogen, Genzyme, Genentech, Teva, and Novartis; and received research funding from Rocky Mountain MS Center, Biogen, Novartis, Acorda, and Alkermes.