OBJECTIVE:To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous haematopoietic cell transplantation (HCT).
METHODS:High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0-5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years post-transplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE).
RESULTS:Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12-72). EFS was 69.2% (90% confidence interval [CI] 50.2-82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%-97.2%), 86.9% (90% CI 69.5%-94.7%), and 86.3% (90% CI 68.1%-94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late
neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of -0.5 (interquartile range -1.5 to 0.0; p = 0.001) among participants who survived and completed the study.
CONCLUSION: HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years.
It is clear that HSCT is amongst the most effective and is probably the most effective immunotherapy. It should be it is replacing the immune system.
The rates of control are very good, but these are selected pwMS, albeit with very active MS, and not the general population. How would this fair if we look at 500 people is a phase III study. The sucess rates of alemtuzumab were good in phase II but dropped in phase III. I would hazard a guess it would be up there. However, will this be a treatment for all…I wonder.
I rather dispare at the risk-averse neurologists that can tolerate MS brains that are battlefields full of clusterbomb holes and still support the softly, softly approach. Its not their brains that are being shredded.
Maybe it would be good to do a Freedom of Information request of prescriptions of each Hospital in UK to see what their neurologists are prescribing. A shedful of beta interferon, alemtuzumab or worse.. nothing. I am sure pharma have this info already. I know we have been FOI’d. I’ld love to have a map of the UK to see who does what.
Would the East End of London be an injectable first line dessert, where would be the oasis of patronisation, doing nothing?
Anyway back to the HSCT, many places have haematology clinics doing cancer treatment and one wonders whether this system has any slack that could be filled by pwMS will to give this approach ago.
Importantly the MS Society have a question of what is the benefit of hard and early treatment as one of their JLA priorities and strategies. Maybe they will be supporting some studies in the UK.
P.S. HSCT depletes B memory cells;-)