Impact of previous disease-modifying treatment on safety and efficacy in patients with MS treated with AHSCT

Abstract

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is a highly effective treatment for multiple sclerosis (MS). The impact of previous long-lasting disease-modifying treatments (DMT) for safety and efficacy of AHSCT is unknown.ObjectiveTo explore whether previous DMTs with long-lasting effects on the immune system (anti-CD20 therapy, alemtuzumab and cladribine) affect treatment-related complications, long-term outcome and risk of new MS disease activity in patients treated with AHSCT.MethodsRetrospective observational study of 104 relapsing remitting patients with MS treated by AHSCT in Sweden and Norway from 2011 to 2021, grouped according to the last DMT used ≤6 months prior to AHSCT. The primary outcomes were early AHSCT-related complications (mortality, neutropenic fever and hospitalisation length), long-term complications (secondary autoimmunity) and proportion of patients with No Evidence of Disease Activity (NEDA-3 status): no new relapses, no MRI activity and no disease progression during the follow-up.ResultsThe mean follow-up time was 39.5 months (range 1–95). Neutropenic fever was a common AHSCT-related complication affecting 69 (66%) patients. There was no treatment-related mortality. During the follow-up period, 20 patients (19%) were diagnosed with autoimmunity. Occurrence of neutropenic fever, hospitalisation length or secondary autoimmunity did not vary dependent on the last DMT used prior to AHSCT. A total of 84 patients (81%) achieved NEDA-3 status, including all patients (100%) using rituximab, alemtuzumab or cladribine before AHSCT.ConclusionThis study provides level 4 evidence that AHSCT in patients previously treated with alemtuzumab, cladribine or rituximab is safe and efficacious.

CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy

“…Since newborn screening for GLD is not widely available ( Wasserstein et al, 2021 ; Schrier Vergano et al, 2022 ), new therapeutic approaches such as immunotherapies may be warranted. Applying immunotherapies could extend the therapeutic window for hematopoietic stem cell transplantation ( Kvistad et al, 2022 ) or enhance long-term outcomes from interventions such as gene therapy ( Heller et al, 2021 ; Hordeaux et al, 2022 ), and therein provide greater benefit to more patients. Future studies to address these issues should examine whether existing FDA-approved immunomodulatory therapeutics can modify GLD disease, both as a monotherapy and as a means to mitigate the early stages of disease and potentially expand eligibility among patients to qualify for other therapies.…”

G-CSF + plerixafor versus G-CSF alone mobilized hematopoietic stem cells in patients with multiple myeloma and lymphoma: a systematic review and meta-analysis

“…For patients with malignant hematological diseases, such as MM, NHL, and HL, AHSCT can potentially prolong survival [ 42–44 ]. Whether sufficient HSCs can be mobilized is the key to the success of transplantation.…”

The Place of Immune Reconstitution Therapy in the Management of Relapsing Multiple Sclerosis in France: An Expert Consensus

“…A recent meta-analysis (2022) showed that, compared with before treatment, aHSCT reduced the frequency of MS relapses, and MRI activity decreased disability (EDSS score), and promoted NEDA (68% of patients) [ 88 ]. Retrospective observational data suggest that aHSCT is effective in patients with insufficient response to previous IRT [ 89 ]. Further observational data suggested that aHSCT was more effective in preventing relapses than fingolimod (hazard ratio [HR] 0.55 [95% CI 0.37–0.91]), with a greater likelihood of improvement in EDSS score (HR 2.62 [95% CI 1.46–4.72]); the efficacy of aHSCT and natalizumab was broadly similar [ 90 ].…”