Summary: A new study reveals immunosupressive therapy coupled with stem cell transplantation can induce sustained remission in RRMS patients.
New clinical trial results provide evidence that high-dose immunosuppressive therapy followed by transplantation of a person’s own blood-forming stem cells can induce sustained remission of relapsing-remitting multiple sclerosis (MS), an autoimmune disease in which the immune system attacks the central nervous system.
Five years after receiving the treatment, called high-dose immunosuppressive therapy and autologous hematopoietic cell transplant (HDIT/HCT), 69 percent of trial participants had survived without experiencing progression of disability, relapse of MS symptoms or new brain lesions. Notably, participants did not take any MS medications after receiving HDIT/HCT. Other studies have indicated that currently available MS drugs have lower success rates.
The trial, called HALT-MS, was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded Immune Tolerance Network (ITN) (link is external). The researchers published three-year results from the study in December 2014, and the final five-year results appear online Feb. 1 in Neurology.
“These extended findings suggest that one-time treatment with HDIT/HCT may be substantially more effective than long-term treatment with the best available medications for people with a certain type of MS,” said NIAID Director Anthony S. Fauci, M.D. “These encouraging results support the development of a large, randomized trial to directly compare HDIT/HCT to standard of care for this often-debilitating disease.”
MS symptoms vary widely and may include motor and speech difficulties, weakness, fatigue and chronic pain. The most common form of MS is relapsing-remitting MS, which is characterized by periods of mild or no symptoms interspersed with symptom flare-ups or relapses. Over years, the disease can worsen and shift to a progressive form.
In HALT-MS, researchers tested the safety, efficacy and durability of HDIT/HCT in 24 volunteers aged 26 to 52 years with relapsing-remitting MS who, despite taking clinically available medications, experienced active inflammation, evidenced by frequent severe relapses, and worsened neurological disability.
The experimental treatment aims to suppress active disease and prevent further disability by removing disease-causing cells and resetting the immune system. During the procedure, doctors collect a participant’s blood-forming stem cells, give the participant high-dose chemotherapy to deplete the immune system, and return the participant’s own stem cells to rebuild the immune system. The treatment carries some risks, and many participants experienced the expected side effects of HDIT/HCT, such as infections. Three participants died during the study; none of the deaths were related to the study treatment.
Five years after HDIT/HCT, most trial participants remained in remission, and their MS had stabilized. In addition, some participants showed improvements, such as recovery of mobility or other physical capabilities.
“Although further evaluation of the benefits and risks of HDIT/HCT is needed, these five-year results suggest the promise of this treatment for inducing long-term, sustained remissions of poor-prognosis relapsing-remitting MS,” said Richard Nash, M.D., of Colorado Blood Cancer Institute and Presbyterian-St. Luke’s Hospital. Dr. Nash served as principal investigator of the HALT-MS study.
“If these findings are confirmed in larger studies, HDIT/HCT may become a potential therapeutic option for patients with active relapsing-remitting MS, particularly those who do not respond to existing therapies,” said Daniel Rotrosen, M.D., director of NIAID’s Division of Allergy, Immunology and Transplantation.
About this genetics research article
Funding: This work was sponsored by NIAID, NIH, and conducted by the ITN under award number AI109565 and NIAID-funded statistical and clinical coordinating centers under award number AI117870. The ClinicalTrials.gov identifier for the Phase 2 study High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is NCT00288626 (link is external).
Source: Hillary Hoffman – NIH/NIAID Image Source: NeuroscienceNews.com image is in the public domain. Original Research: Abstract for “High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS” by Richard A. Nash, MD, George J. Hutton, MD, Michael K. Racke, MD, Uday Popat, MD, Steven M. Devine, MD, Kaitlyn C. Steinmiller, MS, Linda M. Griffith, MD, MHS, PhD, Paolo A. Muraro, MD, PhD, Harry Openshaw, MD, Peter H. Sayre, MD, Olaf Stuve, MD, PhD, Douglas L. Arnold, MD, Mark H. Wener, MD, George E. Georges, MD, Annette Wundes, MD, George H. Kraft, MD and James D. Bowen, MD in Neurology. Published online February 1 2017 doi:10.1212/WNL.0000000000003660
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]NIH/NIAID “Emapthetic People Experience Dogs’ Expressions More Strongly.” NeuroscienceNews. NeuroscienceNews, 5 February 2017. <https://neurosciencenews.com/stem-cell-transplants-ms-6061/>.[/cbtab][cbtab title=”APA”]NIH/NIAID (2017, February 5). Emapthetic People Experience Dogs’ Expressions More Strongly. NeuroscienceNew. Retrieved February 5, 2017 from https://neurosciencenews.com/stem-cell-transplants-ms-6061/[/cbtab][cbtab title=”Chicago”]NIH/NIAID “Emapthetic People Experience Dogs’ Expressions More Strongly.” https://neurosciencenews.com/stem-cell-transplants-ms-6061/ (accessed February 5, 2017).[/cbtab][/cbtabs]
High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS
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.
ClinicalTrials.gov 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.
“High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS” by Richard A. Nash, MD, George J. Hutton, MD, Michael K. Racke, MD, Uday Popat, MD, Steven M. Devine, MD, Kaitlyn C. Steinmiller, MS, Linda M. Griffith, MD, MHS, PhD, Paolo A. Muraro, MD, PhD, Harry Openshaw, MD, Peter H. Sayre, MD, Olaf Stuve, MD, PhD, Douglas L. Arnold, MD, Mark H. Wener, MD, George E. Georges, MD, Annette Wundes, MD, George H. Kraft, MD and James D. Bowen, MD in Neurology. Published online February 1 2017 doi:10.1212/WNL.0000000000003660