Cladribine treatment leads to a selective depletion of memory B-cells in patients with relapsing-remitting multiple sclerosis (RRMS), researchers report.
The results are in the presentation “Cladribine for the Effective Control of Multiple Sclerosis via Memory B Cell Depletion” being given Friday, the final day of the 2018 Annual Meeting of the American Academy of Neurology (AAN).
Originally developed as an anti-cancer agent, cladribine in various forms has shown potential as an RRMS therapy. It works by selectively targeting white blood cells (lymphocytes) associated with MS development.
In this study, cladribine was given as a subcutaneous (under the skin) injection. As an oral treatment under the brand name Mavenclad, developed by Merck KGaA of Darmstadt, Germany, cladribine is an approved RRMS therapy in Europe.
Researchers developed a compassionate-use program for patients ineligible for licensed disease-modifying therapies (DMTs). They aimed to assess specifically the impact of subcutaneous cladribine on a subset of immune cells called memory B-cells. These cells keep a “memory” of past “foreign” (non-human) proteins and are long-lived, generating a faster and stronger response upon re-stimulation with “foreign” invaders.
Memory B-cells are known to impact MS, and several MS therapeutics — such as Novartis’ Gilenya (fingolimod), Biogen’s Tecfidera (dimethyl fumarate), Genzyme’s Lemtrada (alemtuzumab), among others — were shown to decrease the number of memory B-cells.
The team hypothesized that subcutaneous cladribine also successfully depletes memory B-cells, similar to other highly effective DMTs.
Enrolled MS patients received under-the-skin injections of cladribine at doses adapted to an individual based on that patient’s lymphocyte levels to avoid any risk of severe lymphopenia, a massive decrease in white blood cells.
After 12 months, researchers analyzed the patients’ content of memory B-cells.
Results showed that within 12 months, cladribine treatment resulted in a marked decrease — about 85 percent — of memory B-cells (identified as CD19+ B-cells).
“Cladribine selectively induces marked and long-lasting memory B-cell depletion similar to alemtuzumab [Lemtrada] creating a central unifying mechanism of action for cladribine and other highly effective DMT,” the researchers wrote.
The team also emphasized that “personalized dosing based on individual lymphocyte response may de-risk the use of cladribine further.”