Adult; Disability Evaluation; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Multiple Sclerosis, Relapsing-Remitting; Transplantation, Autologous; Treatment Outcome
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;
CONCLUSION: HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years.
CLINICALTRIALSGOV IDENTIFIER: NCT00288626.
CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that participants with RRMS experienced sustained remissions with toxicities as expected from HDIT/HCT.
Neurosciences (Brain & Spine)
Nash, Richard A; Hutton, George J; Racke, Michael K; Popat, Uday; Devine, Steven M; Steinmiller, Kaitlyn C; Griffith, Linda M; Muraro, Paolo A; Openshaw, Harry; Sayre, Peter H; Stuve, Olaf; Arnold, Douglas L; Wener, Mark H; Georges, George E; Wundes, Annette; Kraft, George H; and Bowen, J D, "High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS." (2017). Articles, Abstracts, and Reports. 2414.