A contemporary study has brought light to the efficacy of autologous hematopoietic stem cell transplantation (AHSCT) in patients with active secondary progressive multiple sclerosis (SPMS).¹ In the study, AHSCT was related to a slowdown in disability progression, and a greater opportunity for disability improvement than the standard immunotherapy.¹

SPMS is the second most prevalent type of multiple sclerosis (MS), leading to a progressive reduction in neurological function and daily activity limitations.² In SPMS, disruption of the blood-brain barrier (BBB) has an early effect on immune attack onset, as well as a later effect on the central nervous system (CNS) demyelination and neurodegeneration.³ AHSCT, a preferred therapeutic option in aggressive relapsing-remitting (RR) MS, has drawn conflicting opinions about its efficacy in SPMS.^4,5 While it has been shown to reduce continuous disability accrual (CDA) and normalize the annualized rate of brain atrophy (AR-BVL), CDA may still be primarily driven by inflammation in the SPMS subgroup and should be evaluated independently from any isolated disability worsening.⁴ The study by Boffa et al. thus sought to evaluate the efficacy of AHSCT in lengthening the time to confirm disability progression in comparison with other disease-modifying therapies (DMTs) in SPMS.¹

Data were retrieved from the Italian MS Register to identify SPMS patients who were treated with standard immunotherapy.¹ Out of 2,361 patients included, 1,975 (83.7%) commenced on a DMT and 386 (16.3%) were treatment-naïve, while 81 received AHSCT.¹ The primary endpoint was the cumulative proportion of patients with a 6-month confirmed disability progression (CDP) among patients on AHSCT for active SPMS vs. patients treated with other DMTs.¹ The definition of CDP was a rise of 1 point in the Expanded Disability Status Scale (EDSS) score, or 0.5 points if the baseline EDSS score was ≥5.5.¹

The time to CDP in AHSCT patients was significantly longer than in patients on “other DMTs” (HR=0.50; 95% CI: 0.31-0.81; p=0.005).¹ After 3 and 5 years, the proportion of patients in the AHSCT group free from CDP were 71.9% (95% CI: 58.5-81.5) and 61.7% (95% CI: 47.5-73.1), compared with 58.1% (95% CI: 50.3-64.9) and 46.3% (95% CI: 37.4-54.5) in the “other DMTs” group, respectively.¹

The difference in mean EDSS change was statistically significant (p<0.001) between the 2 groups over the 10 years, with -0.013 EDSS points/year (95% CI: -0.087-0.061) in the AHSCT group, as compared with the “other DMTs” group with +0.157 EDSS points/year (95% CI: 0.117-0.196).¹ Subsequently, the estimated EDSS change per year was -0.017 (95% CI: -0.099-0.065) and +0.18 (95% CI: 0.15-0.21) in the AHSCT and “other DMTs” groups, respectively (p<0.001).¹

The annualized relapse rate (ARR) of the first 2-year follow-up was 0.024 (95% CI: 0-0.051) and 0.32 (95% CI: 0.24-0.39) in the AHSCT and “other DMTs” groups, respectively [Rate ratio (RR)=0.075; 95% CI: 0.023-0.24; p<0.001].¹ The ARR over the entire follow-up period of mean 5.2 years was 0.020 (95% CI: 0.006-0.034) and 0.45 (95% CI: 0.36-0.55), respectively (RR=0.044; 95% CI: 0.021-0.091; p<0.001).¹

The EDSS improvement rate was significantly greater in AHSCT patients when compared with the “other DMTs” patients (HR=4.21; 95% CI: 2.42-7.33; p<0.001).¹ At 1 and 3 years, AHSCT patients who had at least 1 improvement event were 30.2% (95% CI: 20.6-42.8) and 38.8% (95% CI: 28.0-51.9), as compared with 3.4% (95% CI: 1.6-7.0) and 7.8% (95% CI: 4.2-13.3) in the “other DMTs” group, respectively (p<0.001).¹ In the AHSCT group, 34.7% (95% CI: 23.2-46.3) of patients achieved and maintained an improvement status 3 years later, while that of the “other DMTs” group was 4.6% (95% CI: 1.7-8.6).¹ Similarly, 5 years later, it was 18.7% (95% CI: 7.9-29.8) in the AHSCT patients and 4.1% (95% CI: 1.3-8.3) in the “other DMTs” patients.¹ These findings showed that there was a statistically significant efficacy of the AHSCT in delaying the time to first CDP, with 61.7% patients without CPD at 5 years.¹ This added to the ongoing debate of AHSCT’s efficacy, such that it has now been proven to retard the neurological progression in active SPMS patients.¹

In conclusion, AHSCT has an advantage over DMT in slowing the disability aggravation in patients with active SPMS, by targeting compartmentalized inflammation behind the BBB in these patients, thus decreasing the progression of disability.¹ Apart from providing more evidence to AHSCT, the results further supported the theory of ongoing inflammation during progressive MS that requires sufficient immunotherapy.¹