High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS)
Year: 2014
Type: article
Study design: Clinical Trial
Abstract: IMPORTANCE: Most patients with relapsing-remitting (RR) multiple sclerosis (MS) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, in contrast, induce sustained remissions in early MS. OBJECTIVE: To evaluate the safety, efficacy, and durability of MS disease stabilization through 3 years after HDIT/HCT. DESIGN, SETTING, AND PARTICIPANTS: Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) is an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling. Participants are evaluated through 5 years after HCT. This report is a prespecified, 3-year interim analysis of the trial. Thirty-six patients with RRMS from referral centers were screened; 25 were enrolled. INTERVENTIONS: Autologous peripheral blood stem cell grafts were CD34+ selected; the participants then received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before autologous HCT. MAIN OUTCOMES AND MEASURES: The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes: (1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging. Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS: Grafts were collected from 25 patients, and 24 of these individuals received HDIT/HCT. The median follow-up period was 186 weeks (interquartile range, 176-250) weeks). Overall event-free survival was 78.4% (90% CI, 60.1%-89.0%) at 3 years. Progression-free survival and clinical relapse-free survival were 90.9% (90% CI, 73.7%-97.1%) and 86.3% (90% CI, 68.1%-94.5%), respectively, at 3 years. Adverse events were consistent with expected toxic effects associated with HDIT/HCT, and no acute treatment-related neurologic adverse events were observed. Improvements were noted in neurologic disability, quality-of-life, and functional scores. CONCLUSIONS AND RELEVANCE: At 3 years, HDIT/HCT without maintenance therapy was effective for inducing sustained remission of active RRMS and was associated with improvements in neurologic function. Treatment was associated with few serious early complications or unexpected adverse events.
Source: JAMA Neurology
Authors: Richard A. Nash, George J. Hutton, Michael K. Racke, Uday Popat, Steven M. Devine, Linda M. Griffith, Paolo A. Muraro, Harry Openshaw, Peter H. Sayre, Olaf Stüve, Douglas L. Arnold, Meagan E. Spychala, Kaitlyn C. McConville, Kristina M. Harris, Deborah Phippard, George E. Georges, Annette Wundes, George H. Kraft, James D. Bowen
Institutions: Colorado Blood Cancer Institute, Baylor College of Medicine, The Ohio State University, The University of Texas MD Anderson Cancer Center, The Ohio State University Wexner Medical Center, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Imperial College London, City Of Hope National Medical Center, University of California, San Francisco, Immune Tolerance Network, University of California San Francisco Medical Center, VA North Texas Health Care System, The University of Texas Southwestern Medical Center, Montreal Neurological Institute and Hospital, NeuroRx Research (Canada), McGill University, Rho (United States), University of Washington, University of Washington Medical Center, Fred Hutch Cancer Center, Swedish Medical Center
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2088520442