A new head-to-head trial has reported that nonmyeloablative hematopoietic stem-cell transplantation is superior to disease-modifying drugs (DMD) with respect to time to disease progression in patients with highly-active relapsing-remitting multiple sclerosis (Burt et al. JAMA 2019;321:165-174).

Over a 10-year period, 110 patients (66% female, mean age 36 years) were enrolled in the study. All subjects had experienced at least two relapses in the prior year while on a DMD and had an EDSS score of 2.0-6.0. Patients were randomized to receive HSCT (with cyclophosphamide 200 mg/kg and antithymocyte globulin 6 mg/kg) or drug treatment. At entry, the prior DMD was switched to a different class of drug or a higher-efficacy agent at the discretion of the investigator. Treatments included natalizumab, dimethyl fumarate, fingolimod and mitoxantrone. Other drugs used were corticosteroids, cyclophosphamide and rituximab. A total of 98 patients were evaluated at 1 year; 23 were evaluated annually for five years. Mean follow-up was 2.8 years.

Overall, disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMD group. The median time to progression was 24 months with drug treatment and could not be calculated due to too few events in the HSCT group (hazard ratio 0.07). At one year, the mean EDSS score improved (from 3.38 to 2.36) in the HSCT group and worsened (from 3.31 to 3.98) in the DMD group. There were no deaths or grade 4 nonhematologic toxicities reported in the HSCT group.

An interim analysis was presented at the American Academy of Neurology annual meeting last year (Burt et al. AAN 2018; abstract (S36.004). However, in that report the primary endpoint was treatment failure, defined as an increase in EDSS score >1 point sustained for 6 months. The rate of treatment failure was 6% with HSCT versus 60% with DMDs.

Prior studies of HSCT in MS have suggested that the benefits of transplantation are sustained over the longer term. A Canadian phase II study of immunoablation followed by autologous HSCT in 24 MS patients reported a disease-free survival rate at three years of 69.6% (Atkins et al. Lancet 2016;388:576-585). One-third of patients had a sustained improvement in EDSS score. There was one death.

In the phase II HALT-MS trial, which also used high-dose immunosuppression followed by aHSCT, the rate of progression-free survival was 91.3% after a median follow-up of 62 months (range 12-72 months) (Nash et al. Neurology 2017;88:842-852). Moreover, 86.9% of patients were relapse-free and 86.3% had no disease activity on MRI at five years.