"Inexpensive" B cell depletion. Low dose IT rituxan...

A board to discuss the anticipated multiple sclerosis treatment Rituxan.
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Anonymoose
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"Inexpensive" B cell depletion. Low dose IT rituxan...

Post by Anonymoose » Mon Jul 13, 2015 6:30 am

http://www.ncbi.nlm.nih.gov/pmc/article ... 003053.pdf
Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally
ABSTRACT
Objective: We are conducting an open-label phase 1b study on the efficacy of intrathecal (IT) administration of rituximab, provided via an Ommaya reservoir, for the treatment of progressive multiple sclerosis (PMS). The objective of this initial study was to monitor B lymphocytes in peripheral blood (PB) and CSF from the first 10 patients 1 year posttreatment.
Methods: Dose titration was performed with daily escalation from 1 mg to 25 mg IT rituximab (n 5 3). Lymphocyte subpopulations were monitored daily during dose escalation in PB by flow cytometry and subsequently every 3 months for 1 year, after a total dose of 3 3 25 mg. PB B-lymphocyte subpopulations for the remaining patients (n 5 7) were monitored at regular intervals. CSF lymphocyte subpopulations for all patients were monitored by flow cytometry every 2–3 months.
Results: The PB B-lymphocyte count dropped rapidly after the first 2 injections (total dose of 3.5 mg IT rituximab) to undetectable levels. Three 25-mg doses given once per week depleted peripheral B lymphocytes entirely for the following 3–6 month period.
Conclusions: Monoclonal antibodies seem to rapidly redistribute to the peripheral compartment following IT injection. Ultra-low doses of rituximab given IT are sufficient to cause complete depletion of peripheral B lymphocytes, indicating that low-dose IT treatment has the potential to be effective in both the CNS and systemic compartments.
Classification of evidence: This study provides Class IV evidence that for patients with PMS, rituximab provided via an Ommaya reservoir depletes peripheral blood B lymphocytes. Neurol Neuroimmunol Neuroinflamm 2015;2:e79; doi: 10.1212/NXI.0000000000000079
More detail and graphs at link.

This would cost astronomically less than the traditional rituxan protocol...and no hours on end sitting in the infusion center. I would think this would open doors for a lot of people. I also think if I ever give rituxan another go, I'll save my $$ by going this route (last time did IT and IV). The LPs really aren't that bad...especially if you are saving $23000!

Good news!! :)

EricDrake
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Re: "Inexpensive" B cell depletion. Low dose IT rituxan...

Post by EricDrake » Mon Jul 13, 2015 9:09 am

Strange that they are still investigating rituximab in PMS, as far as I know they already had a trial for that:
http://www.ncbi.nlm.nih.gov/pubmed/19847908
I mean the old one shown some minor results but not such a big breakthrough and this new study does not mention anything about disease progression, strange.

Anonymoose
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Re: "Inexpensive" B cell depletion. Low dose IT rituxan...

Post by Anonymoose » Mon Jul 13, 2015 9:39 am

I think the new pms-rituxan studies are exploring the possibility that the treatment failed because IV administration barely penetrates the cns. The assumption is that it works in rrms because the bbb is open and therefore the rituxan can get into the cns. I believe this logic is also part of the suitability criteria for hsct protocols...no relapses, no joy or something like that. The new studies all have an IT component. There is conflicting information out there regarding the usefulness of rituxan in the cns. Some claim the cns B cells aren't cleared out by IT rituxan. Others claim they do. Based on successful use of IT rituxan for CNS lymphomas that were NOT managed by IV rituxan, I think the cns B cells are cleaned up by IT rituxan. I'm not a doctor though...just a rampant speculator.

To me, the importance of the linked paper isn't its effectiveness in controlling PMS. What's important is that for those that rituxan will help, it suddenly has become more financially achievable. Insurance usually won't pay for rituxan for ms so it's a huge out of pocket expense when administered the traditional way. The impossible becomes possible.

Rituxan is an old, relatively safe biologic. It doesn't carry the same risks big pharma's rituxan replacement for big $$$ does. This isn't the first study that has demonstrated the pb B cell depletion with low dose IT rituxan. The researchers are repeatedly making this point. I hope that translates into more affordable and effective treatments for pwms.

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