High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS

Area of Science:

• Neurology
• Immunology
• Hematology

Background:

• Multiple Sclerosis (MS) is a chronic, immune-mediated disease affecting the central nervous system.
• Relapsing-remitting MS (RRMS) is characterized by distinct neurological relapses followed by periods of remission.
• High-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (HCT) is an intensive treatment strategy explored for aggressive autoimmune diseases.

Purpose of the Study:

• To assess the safety, efficacy, and long-term durability of HDIT/HCT in patients with active relapsing-remitting multiple sclerosis (RRMS).
• To evaluate disease stabilization, including event-free survival (EFS), progression-free survival, and relapse-free survival.
• To monitor adverse events (AE) associated with HDIT/HCT and assess neurological disability changes.

Main Methods:

• The High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) trial enrolled patients with RRMS experiencing relapses and disability progression (EDSS 3.0-5.5) despite existing therapies.
• Participants underwent HDIT/HCT, and were monitored for 5 years post-transplant.
• Primary endpoint was event-free survival (EFS), defined as survival without death or disease activity (disability progression, relapse, or new MRI lesions). Adverse events were graded using NCI-CTCAE criteria.

Main Results:

• Twenty-four of twenty-five evaluated participants received HDIT/HCT, with a median follow-up of 62 months.
• Event-free survival (EFS) at 5 years was 69.2%. Progression-free, relapse-free, and MRI activity-free survival rates were 91.3%, 86.9%, and 86.3%, respectively.
• Adverse events were consistent with expected toxicities of HDIT/HCT, with no significant late neurological adverse effects. A significant improvement in neurological disability was observed (median EDSS change -0.5, p=0.001).

Conclusions:

• HDIT/HCT, without maintenance therapy, demonstrated effectiveness in achieving long-term sustained remissions in patients with active RRMS.
• The treatment was associated with expected toxicities, but showed significant improvements in neurological disability.
• This approach offers a potential therapeutic option for managing aggressive RRMS.