If CD19 is still zero 6 months after Ocrevus infusion, is it safe to postpone the next infusion until B cells have started to repopulate?

Here is my Question:
First, thank you for your continued support and advice, I've learned so much from your Virtual MS Center. On your blog post, Is there information on the long-term impact of B cell depletion therapies (whether treating MS or otherwise)?,  I wanted to ask if there is yet a way to determine whether the cells which return during the bone marrow repletion process are less autoreactive and/or better regulated? I'm hoping you will say yes, but I suspect you'll say no, not yet anyway.

Another question: in general, if CD19 is still zero 6 months after Ocrevus infusion, is it safe to postpone the next infusion until B cells have started to repopulate?

Answer:

You are correct. At present we have no validated way to determine if the differentiated B cells which return post repletion are less autoreactive or, to reverse the question, when they can become less regulated and more autoreactive. We can look at the clonal size of certain autoreactive cells, but this still only tells us about structure and this information has not been associated with measures of actual MS disease activity.

Can you postpone an Ocrevus infusion if CD19+ B cells are undetectable? You actually asked if it is "safe" to postpone infusions, but I am not sure what that means. The risks of postponing infusions in a relapsing or progressive MS patient are small. The real question is how long can you postpone infusions? We really do not know the answer to this question, but there you can ask how long is it safe to continue infusions every 6 months. This answer will depend on many factors including age, prior treatments, comorbid conditions, level of disability and how long you've been on Ocrevus or another anti-CD20 agent. Certainly, if you have an increased risk of infection or demonstrate increased infections on treatment or if your IgG level drops too much, then the risks may be considered too high. These are all individual decisions you must make with a clinician you trust who knows your condition and your goals of therapy.

Revere P (Rip) Kinkel, MDProfessor of Neurosciences
Director of the Multiple Sclerosis Program
University of California San Diego