#AANAM – Exploring Mavenclad’s Effects on Immune Cells

Editor’s note: The Multiple Sclerosis News Today team is providing in-depth coverage of the 2021 Virtual AAN Annual Meeting, held April 17–22. Go here to read stories from the conference.

After starting treatment with the multiple sclerosis (MS) therapy Mavenclad (cladribine), some types of immune cells are more affected than others, a new analysis suggests.

The findings may have important implications for understanding how Mavenclad works in MS patients, as well as understanding how vaccines still may be effective in people taking this immune-suppressing therapy.

The results were presented recently at the 2021 virtual American Academy of Neurology Annual Meeting (AANAM), in the talk, “Characterization of Peripheral Immune Cell Dynamics and Repopulation Patterns in the First 12 Months of Cladribine Tablets Treatment: MAGNIFY-MS Study.”

Mavenclad is an approved treatment for active relapsing forms of MS in the U.S. Originally developed to treat certain cancers, Mavenclad is believed to work by reducing levels of immune cells that drive inflammation in MS. However, it’s not clear exactly how immune cell dynamics are affected by Mavenclad treatment, or how these dynamics are tied to changes in MS symptoms following treatment.

At AANAM, Heinz Wiendl, MD, a professor at the University of Münster in Germany, shared data from the clinical trial MAGNIFY-MS (NCT03364036), which aims to address these questions. MAGNIFY-MS is sponsored by EMD Serono (Merck KGaA outside of the U.S. and Canada), which markets Mavenclad.

Wiendl shared data from 57 people with highly active relapsing MS who were treated with Mavenclad for a year in the trial. The patients’ median age was 37 years, 61% were female, and nearly three-quarters had experienced two or more MS relapses in the year before starting the trial.

After one, two, three, six, and 12 months of treatment, participants’ blood was drawn, and researchers analyzed different populations of immune cells to see how they were affected. The researchers also assessed levels of antibodies, also called immunoglobulins, which are proteins made by the immune system that fight infection.

The results broadly showed that different types of immune cells were affected differently by Mavenclad treatment. Specifically, shortly after starting treatment, levels of B-cells — the immune cells primarily responsible for making antibodies — decreased sharply. As treatment continued over time, levels of some specific subtypes of B-cells increased to near levels prior to treatment, while others remained at low levels through a year of treatment.

“You have a very quick drop in many, many B-cell subpopulations, with a recovery of some of them, but not all of them,” Wiendl said.

More specifically, data suggested that Mavenclad treatment substantially reduced levels of memory B-cells, while another type — naïve B-cells —  recovered quickly. Notably, memory B-cells are thought to be major drivers of the inflammation that damages the nervous system in MS.

Wiendl said this “might indicate that this contributes to the long-term effect of [Mavenclad] and might have implications for individual durability of the treatment effect,” though he noted that more data is needed to be sure.

Also notable, particularly in the setting of the present pandemic, it is the naïve B-cells that are generally more important in mounting the type of immune response by which vaccines exert their protective effect.

“These important data indicate that in addition to addressing MS relapses and progression, patients treated with Mavenclad may be able to simultaneously mount a proper vaccine response — a particularly important finding at this time,” Wiendl said in a press release.

In contrast to the dramatic effects on B-cells, levels of other types of immune cells (specifically T-cells and natural killer cells) showed a more modest decrease after beginning Mavenclad treatment, and remained generally stable through a year of the therapy.

Levels of antibodies in participants’ blood also did not substantially change over the course of a year of Mavenclad therapy.

“The findings presented at [AANAM] further our understanding of how Mavenclad impacts the immune system, and how it may exert a therapeutic effect in patients with multiple sclerosis while repopulating cells which support immune responses,” Wiendl said.