Long-Lasting DMT Use Prior to Stem Cell Transplant Shows No Impact on Efficacy, Safety


Although neutropenic fever was common among patients, there was no significant difference between disease-modifying therapies, including those with long-lasting effects.

Oivind Torkildsen, MD, PhD, Department of Neurology, Haukeland University Hospital

Oivind Torkildsen, MD, PhD

Recently published retrospective, observational data showed that prior use of either alemtuzumab (Lemtrada; Sanofi Genzyme), cladribine (Mavenclad; EMD Sorono), or rituximab (Rituxan; Genentech) did not impact the frequency of early and late adverse events (AEs) following autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsing multiple sclerosis (MS).1

In a cohort of 104 individuals, 81% (n = 84) achieved No Evidence of Disease Activity (NEDA)-3 status, including 100% of all patients on either of those 3 disease-modifying therapies (DMTs) before AHSCT. Neutropenic fever, a common AHSCT-related complication that was reported in 66% (n = 69) of the sample, was not associated with any specific DMT.

Senior investigator Oivind Torkildsen, MD, PhD, Department of Neurology, Haukeland University Hospital, and colleagues aimed to explore whether previous DMTs with long-lasting effects on the immune system affected treatment-related complications, long-term outcome, and risk of new MS disease activity. The cohort had a mean number of 2.1 prior DMTs used, while 16.3% (n = 17) had used at least 4 DMTs.

In total, 76% (n = 79) of the patients had been exposed to a DMT in the 6 months prior to AHSCT, with a mean follow-up time of 39.5 months (range, 1-95). DMTs with long-lasting effects—the aforementioned rituximab, alemtuzumab, and cladribine—were used in 25% (n = 26) of the sample. The rest of the patients had been treated with natalizumab (Tysabri; Biogen), fingolimod (Gilenya; Novartis), interferons, dimethyl fumarate, glatiramer acetate, and teriflunomide (Aubagio; Sanofi).

All cases of neutropenic fever were treated by intravenous antibiotics. DMTs with long-term effects on the immune system made up 29% (n = 20) of these cases. There was no treatment-related mortality and all patients who needed inpatient care were discharged from the hospital within 23 days.

Evidence of disease activity was found in 19% (n = 20) of the sample during the follow-up period, including increases of 1 to 3 points in patients with Expanded Disability Status Scale scores between 4.0 and 5.5. Among those with disease activity, 9 had new relapses and MRI activity, 8 only had new MRI activity, and 3 had sustained disease progression. The time span before new disease activity varied from 1 to 64 months after AHSCT.

READ MORE: The Current State and Future Promise of Neurology

In terms of late AEs, 19% (n = 20) of the cohort had a secondary autoimmune disease recorded in the follow-up period. Of them, 10% (n = 11) and 7% (n = 7) were hyperthyroidism and hypothyroidism, respectively. The remaining AEs were one patient with hypothyroidism and psoriasis vulgaris (1%) and one patient (1%) with autoimmune thrombocytopenic purpura. Secondary autoimmunity was found in 4% of those treated with a DMT with a long-lasting effect, which was not statistically significantly different from other pre-AHSCT DMTs. Notably, 2 patients previously treated with alemtuzumab were diagnosed with hyperthyroidism.

The use of stem cells to treat patients with MS has become more of a reality than phenomenon in recent years. One notable innovation, BrainStorm Cell Therapeutics’ NurOwn autologous mesenchymal stromal cells secreting neurotrophic factors (MSC-NTF) cells, has made headway in the field, capped off by a positive phase 2 study in patients with progressive MS. In March 2021, the company announced the approach met its primary end point of safety, with 80% of the 18-patient cohort completing the study. Procedure-related AEs resulted in 2 patients discontinuing.2

Efficacy outcomes of NurOwn were compared with a 48-patient matched clinical cohort from the Comprehensive Longitudinal Investigations in MS at the Brigham & Women’s Hospital study. All told, 38% of patients who received the treatment showed at least a 10-point improvement in the 12-Item MS Walking Scale from baseline to week 28.

In October 2021, MS expert Jeffrey Cohen, director of the Mellen Center for MS Treatment and Research at Cleveland Clinic, discussed the use of MSC-NTF cells in progressive MS and the benefits they may bring. Watch below as he details the intrigue behind this approach.

1. Kvistad SA, Burman J, Lehmann AK, et al. Impact of previous disease-modifying treatment on safety and efficacy in patients with MS treated with AHSCT. J Neurol Neurosurg Psychiatry. Published online May 4, 2022. doi:10.1136/jnnp-2022-328797
2. BrainStorm announces positive topline data in phase 2 study evaluating NurOwn as a treatment for progressive MS. News release. BrainStorm Cell Therapeutics. March 24, 2021. Accessed May 23, 2022. https://www.prnewswire.com/news-releases/brainstorm-announces-positive-topline-data-in-phase-2-study-evaluating-nurown-as-a-treatment-for-progressive-ms-301254709.html
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