Autologous Hematopoietic Stem Cell Transplantation Fails to Show Superiority to Natalizumab as a Treatment for Progressive MS

Tomas Kalincik, MD, PhD

In a recent comparator study, autologous hematopoietic stem cell transplantation (AHSCT) proved to not be more beneficial for reducing disability progression than natalizumab (Tysabri; Biogen) among patients with progressive multiple sclerosis (MS).¹ These findings were presented in a late-breaking session at the 2022 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held October 26-28, in Amsterdam, Netherlands.

All told, those treated with AHSCT (n = 39) experienced comparable on-treatment frequency of relapses as the matched cohort on natalizumab-(n = 65). In the pairwise censored group, the annualized relapse rate (ARR) mean was 0.08 (±0.28) for the AHSCT-treated patients and 0.07 (±0.25) for natalizumab treated patients (HR for relapses, 1.04; 95% CI, 0.39-2.81) over the span of up to 6 years.¹

“In this combined multicentric study, we can conclude that AHSCT is not superior to natalizumab in reducing disability progression, facilitating disability improvement, or in reducing subsequent relapses. Complications of AHSCT are common, but fortunately among the 39 patients, we did not report any treatment related to mortality,” Tomas Kalincik, MD, PhD, head of the Clinical Outcomes Research Unit, University of Melbourne, said during the presentation.

Recruitment for patients with secondary or primary MS came from 6 AHSCT MS centers in Ottawa, Uppsala, Sheffield, Bergen, Sydney, and Melbourne. The patients collected from these MS centers were then combined with other patients from the MSBase registry. Patients were matched on a propensity score which included categories of sex, age, disability score (EDSS), the number of relapses before baseline at 12 and 24 months, time from the MS onset, the most effective prior therapy, and the country. Investigators included pairwise-censored groups which were compared on ARR, freedom from relapses, and cumulative hazards of 6-month confirmed EDSS worsening.

Kalincik said in the oral presentation, “Among the treated, we used pairwise censoring to preserve the quality of the match throughout the comparison to follow up. The matching may have improved the closeness of the compared groups when we compare the distances before matching to after matching.”

Of those treated with AHSCT (n = 39), 37were diagnosed with secondary progressive MS. The majority of patients were women (64%), and the mean age of the cohort was 37 years. Notably, the mean EDSS was 5.7 along with recent pre-baseline EDSS progression (28%) and relapse mean rate of 0.5 that was recorded during the preceding year. At the conclusion of the study, the cumulative hazards of 6-month EDSS worsening (HR 1.50, 95% CI, 0.22-10.26) and the improvement (HR, 1.49, 95% CI, 0.70-3.13) were also similar.

“In this matched cohort, the annualized relapse rate after the baseline was low as 0.08. This is significant when we consider that this patient had a high relatively high degree of activity prior to the baseline, as one would expect from enrollment in the HSCT treatment regimens. Most importantly, we find no difference in the ARR between the HSCT and natalizumab cohorts. In both cohorts, the value of the ARR was 0.08, which was also corroborated by the cumulative hazard analysis of the probability of relapse,” Kalincik said in his presentation.

There were 3 patients from the AHSCT group that experienced febrile neutropenia during mobilization. Additionally, 9 patients from the same arm experienced serum sickness,6 patients required ICU admission, and 36 patients experienced complications after discharge; of these, 21 had infectious complications. Overall, there were no reports of treatment-related deaths.

Kalincik added to his oral presentation, stating “The patients with progressive MS tended to accumulate disability more often than those with relapsing MS, and unlike in relapsing MS, where you see the stabilization of disability, we do not see the same trend in progressive disease.”

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REFERENCES
1. Kalincik T, Sharmin S, Roos I, et al. Effectiveness of autologous haematopoietic stem cell transplantation in comparison with natalizumab in progressive MS. Presented at: ECTRIMS Congress 2022; October 26-28; Amsterdam, Netherlands. Late Breaking Oral Abstract