Background
Although a variety of disease-modifying therapies (DMTs) are available to treat the damaging inflammation that affects people with relapsing-remitting MS (RRMS), DMTs are only partially effective and two-thirds of people with MS are reported to experience breakthrough disease activity despite treatment. Furthermore, people with RRMS treated with DMTs are often reliant on these medications for many years, since discontinuation of treatment can lead to rebound of MS symptoms. An alternative to first-line DMTs that has been under investigation includes cell-based therapies. High-dose immunosuppressive therapy (HDIT) combined with hematopoietic cell transplant (HCT) is one potential cell-based approach that is gaining interest among the MS research community. The aim of the treatment is to effectively remove disease-causing immune cells and then reset the immune system by transplanting an individual’s own bone marrow-derived stem cells. Similar treatments have been conducted in Canada, notably the MS Scientific Research Foundation (MSSRF)-funded Canadian Bone Marrow Transplantation (BMT) trial, which led to absence of new lesions and reduction in disability in people with aggressive forms of MS.
The Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) study group recently published preliminary findings at the 3-year mark of the 5-year-long study. The authors of the study, which include MS Society-funded researcher Dr. Douglas Arnold, set out to investigate both the effectiveness and safety profile of early intervention with HDIT/HCT in the control of inflammation and maintenance of remission in people with RRMS.
The Study
HALT-MS is a multi-centre, phase II clinical trial with 24 participants currently enrolled in the study and receiving treatment. Eligible participants are adults with RRMS who have been unsuccessfully treated with DMTs within 18 months prior to enrolment. Hematopoietic stem cells – stem cells originating in the bone marrow that develop into different types of blood cells – were harvested from blood samples from each participant, purified and stored. Participants were then exposed to a high-dose cocktail of chemotherapy drugs to eliminate the immune system in preparation for infusion with their own hematopoietic stem cells – a process referred to as autologous stem cell transplantation.
The researchers evaluated the effectiveness of the treatment by measuring the probability of event-free survival; in other words, survival without death or confirmed clinical relapse, loss of neurologic function, or new lesions in the brain detected by magnetic resonance imaging (MRI). They also evaluated drug safety by observing adverse events (AE). This is a single-arm study, meaning all participants received the treatment, and measurements taken over time were compared to a participant’s condition before the start of treatment.
Results
The study found that at the 3-year mark, combined HDIT/HCT therapy induced sustained remission of active RRMS along with improvements in neurologic function. Event-free survival was calculated to be 82.8% at 2 years and 78.4% at 3 years in the 24 participants who underwent the treatment. Moreover, participants overall experienced an improvement in neurologic function over 3 years based on clinical assessments. Some AEs were observed, although these were consistent with what is expected from aggressive HDIT, and most toxic effects were either managed effectively or resolved over time.
Comment
Treatment of RRMS with conventional DMTs can reduce relapses, but full remission along with improvement in neurologic function continues to be elusive. The preliminary results of this study offer hope to people with RRMS who are unresponsive to DMTs, since most of the participants undergoing HDIT/HCT therapy exhibited remission after three years along with improvements in neurologic function. This study adds to the knowledge and success achieved by the MSSRF-funded Canadian BMT trial which, in addition to managing disease activity in participants, advanced our understanding of the immunological changes that underlie relapses in people with MS. Nonetheless, HDIT/HCT is an aggressive therapy that presents substantial toxicity and risks. Thus, completion of the 5-year study along with a detailed analysis of the results is required before conclusions can be drawn about the long-term benefits of this therapy for people living with MS.
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. 2014 Dec. [Epub Ahead of Print]