High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS

Richard A. Nash, George J. Hutton, Michael K. Racke, Uday Popat, Steven M. Devine, Kaitlyn C. Steinmiller, Linda M. Griffith, Paolo A. Muraro, Harry Openshaw, Peter H. Sayre, Olaf Stuve, Douglas L. Arnold, Mark H. Wener, George E. Georges, Annette Wundes, George H. Kraft, James D. Bowen

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Abstract

Objective: To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT). Methods: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0-5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE). Results: Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12-72). EFS was 69.2% (90% confidence interval [CI] 50.2-82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%-97.2%), 86.9% (90% CI 69.5%-94.7%), and 86.3% (90% CI 68.1%-94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of -0.5 (interquartile range -1.5 to 0.0; p = 0.001) among participants who survived and completed the study. Conclusion: HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years.

Original languageEnglish (US)
Pages (from-to)842-852
Number of pages11
JournalNeurology
Volume88
Issue number9
DOIs
StatePublished - Feb 28 2017

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ASJC Scopus subject areas

  • Clinical Neurology

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Nash, R. A., Hutton, G. J., Racke, M. K., Popat, U., Devine, S. M., Steinmiller, K. C., Griffith, L. M., Muraro, P. A., Openshaw, H., Sayre, P. H., Stuve, O., Arnold, D. L., Wener, M. H., Georges, G. E., Wundes, A., Kraft, G. H., & Bowen, J. D. (2017). High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology, 88(9), 842-852. https://doi.org/10.1212/WNL.0000000000003660