A new study published online before print in the journal JAMA Neurology reports that three years on, most members of a small subject group of patients with active relapsing-remitting (RR) multiple sclerosis (MS) who had received an experimental high-dose immunosuppressive therapy (HDIT) followed by a transplant of their own hematopoietic stem cells, remain in sustained remission with lasting neurological function improvement.
The Open Source research update, entitled “High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) – A 3-Year Interim Report,” (JAMA Neurol. Published online December 29, 2014; DOI: 10.1001/jamaneurol.2014.378) is coauthored by Richard A. Nash, MD, George J. Hutton, MD; Michael K. Racke, MD; Uday Popat, MD; Steven M. Devine, MD; Linda M. Griffith, MD, PhD; Paolo A. Muraro, MD, PhD; Harry Openshaw, MD; Peter H. Sayre, MD, PhD9,10; Olaf Stüve, MD, PhD11,12,13; Douglas L. Arnold, MD; Meagan E. Spychala, DrPH; Kaitlyn C. McConville, MS Kristina M. Harris, PhD; Deborah Phippard, PhD; George E. Georges, MD, Annette Wundes, MD; George H. Kraft, MD, MS, and James D. Bowen, MD, representing 22 different medical research institutions in the U.S..Canada, and the U.K.
In an article study, lead author Richard A. Nash, M.D. of the Colorado Blood Cancer Institute at Presbyterian/St. Luke’s Medical Center, Denver, and coauthors report on the safety, efficacy and sustainability of MS disease stabilization though three years after the procedures.
The coauthors observe that most patients with relapsing-remitting multiple sclerosis who are treated with approved disease-modifying therapies will experience breakthrough disease and accumulate neurologic disability. However RRMS patient participants in a clinical trial who received high-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, by contrast, experience sustained remissions in cases of MS treated early.
The update published this week in JAMA Neurology evaluates the safety, efficacy, and durability of MS disease stabilization achieved in the three years after the HDIT/HCT therapy was administered to a group of 25 participants, 24 of whom ultimately received the experimental treatment.
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 have experienced relapses involving neurologic function loss during treatment with other disease-modifying therapies within 18 months prior to enrolment. Participants are to be evaluated through five years after receiving the HCT treatment, and this report is a scheduled three-year interim analysis of the trial in which autologous peripheral blood stem cell grafts were CD34+ selected, after which participants received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before receiving autologous HCT.
The main end point objective of HALT-MS is “event-free survival,” which is defined as survival without death or disease activity from any of specified outcomes: 1) confirmed loss of neurologic function, 2) clinical relapse, or 3) observation of new lesions using magnetic resonance imaging (MRI). Any toxic effects associated with the experimental treatment are to be reported using National Cancer Institute Common Terminology Criteria for Adverse Events. The median follow-up interval was 186 weeks, and overall event-free survival averaged 78.4% (ranging 90% CI, 60.1%-89.0%) at the three year mark. Progression-free survival and clinical relapse-free survival were 90.9 percent and 86.3 percent, respectively, at three years. The researchers report that adverse events observed were consistent with what had been expected with HDIT/HCT, and no acute treatment-related neurologic adverse events were observed. Improvement was observed in subjects’ neurologic disability, quality-of-life, and functional scores.
The scientists conclude that at the three-year mark in the trial, HDIT/HCT without and maintenance therapy was observed to be effective at inducing sustained remission of active RRMS and also associated with neurologic function improvements, and only a few serious early complications or unexpected adverse events.
The JAMA Neurology report’s coauthors note that researchers have been investigating autologous hematopoietic cell transplant (HCT) therapy for more than 20 years — the hoped-for objective being removal of disease-inducing immune cells and an immune system reset. However, many patients with advanced disabilities and progressive forms of MS who participated in early clinical trials of high-dose immunosuppressive therapy (HDIT)/HCT continued to lose neurologic function, consistent with the noninflammatory factors and progressive neurodegeneration associated with these stages of the disease. However in 15 years of monitoring, patients with active central nervous system inflammation before HDIT/HCT enjoyed significantly better outcome compared with those without active inflammation before HDIT/HCT, indicating that the therapy may achieve greater success if received in earlier MS inflammatory stages.
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