Autologous Hematopoietic Stem Cell Transplant for Relapsing-Remitting MS

SYNOPSIS: This study analyzes relapsing-remitting multiple sclerosis patients treated with high-dosage immunosuppressants coupled with autologous stem cell transplant, displaying promising sustained disease control dampened by the treatment’s potential risk.

SOURCE: Nash RA, et. al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): A 3-year interim report. JAMA Neurol 2015;72:159-169.

Relapsing-remitting multiple sclerosis is an inflammatory/neurodegenerative disease typified by periods of drastic inflammation followed by remission. If left untreated, RRMS can progress into a primarily neurodegenerative secondary stage, in which relapses are followed by incomplete and progressively weaker remissions. Treatments tend to be most effective in the primary inflammatory, relapsing phase, specifically immunomodulation treatment, which unfortunately reveals little positive effects in treatment during the progressive neurodegenerative phase. There are currently 10 relapsing MS treatments approved by the FDA, each with different immune effects and benefit/risk profile. This variability of available medication has not, however, prevented the majority of patients’ bodies from resisting treatment. The majority of these treatments, furthermore, require continuity to sustain efficacy, giving rise to a whole host of issues regarding patient compliance and the potential for adverse side effects. A shorter duration treatment that could provide long-term relief would be a preferable route and the discovery of such a treatment would prove to be a huge boon to MS research. One potential such MS treatment, autologous hematopoietic stem-cell transplantation, was explored in the current study, deemed HALT-MS.

A continuous 5-year study, HALT-HS tested RRMS patients aged 18-60 who had been diagnosed less than 15 years prior and who had had at least two relapses in the previous year and a half. Filgrastim was used to stimulate hematopoietic stem-cell mobilization, while patients also underwent an intense chemotherapy regimen. To minimize risk of relapse during stem cell transplantation, patients took prednisone orally during periods of mobilization. At biannual marks during the first year and then annually from thereafter, comprehensive clinical evaluations including brain MRI testing ensured that information would be reasonably up to date. Patients displaying relevant neurological symptoms between yearly measurements were also brought in for evaluation.

The study subjected 24 RRMS patients to autologous hematopoietic stem cell transplantations (HDIT HCT) preceded by high-dose immunosuppressive therapy. The median time each patient had had the disease at the baseline testing was 4.9 years while their median expanded disabilities status scale score was a 4.5. The primary endpoint the study emphasized was the amount of time before a treatment failed. Treatment failure was defined as cases resulting in death, disease progression (increase in EDSS), significant relapse, or increase in T2 brain lesions displayed by MRI.

After three years the probability of event-free survival was calculated to be 78.4%. on average EDSS among the patients improved over the course of treatment. None of the compliant patients developed the lesions that would denote a treatment failure. Brain volume amongst compliant patients seemed appeared to stabilize after the 6-month mark. Every patient, however, experienced a severe, life-threatening adverse event — although the majority were expected and either reversible or treatable. Two patients died, one due to disease progression that was not halted and another due to a worsened pre-existing non-neurological condition. Elsewhere, rapid disease progression and/or death predicated by hematopoietic stem-cell transplantation have also been reported, further casting doubt on the feasibility of HDIT/HCT as an effective and safe short-term treatment.