given the risks of PML with Rituximab, is HSCT safer for people with SPMS and positive JC virus (value being 3.84)?

Question:
Given the risks of PML with Rituximab, is HSCT safer for people with SPMS and positive JC virus (value being 3.84)?

Answer:
The risk of PML on rituximab is actually very low.The most recent publication on the risk of PML for FDA approved inflammatory conditions is 2.5 per 100,000 people treated. This is lower than the risk of PML with tecfidera and gilenya (which are also low risk by the way but certainly associated with PML) and much lower than the risk of PML with tysabri.

HSCT (hematopoietic stem cell transplantation) has only been demonstrated to be effective in Relapsing Remitting MS (NOT SPMS), and is generally reserved for people with severe aggressive MS (SAMS), failing one or two prior DMTs.  All of the HSCT studies in SPMS demonstrate a higher risk of complications, including death, in SPMS and less overall effectiveness compared to the treatment effects observed in RRMS. However, as of now there has NOT been a randomized controlled study of HSCT in SPMS, so further studies may demonstrate effectiveness in a subgroup of patients with SPMS.

It is very hard to know at present if there is an increased risk of PML in MS patients after HSCT, since less than 3000 people with MS worldwide have been treated with HSCT and tracked in ongoing registries. PML has certainly been reported in people receiving HSCT for other conditions. There are additional severe risks with HSCT other than PML, and this treatment should only be used in experienced centers with an independent review board that ensures patients are selected carefully for treatment.

Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego