#AANAM – Blacks, Whites Respond Differently to B-cell Targeting Therapies

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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B-cell targeting therapies

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Common B-cell depleting therapies, such as rituximab and Ocrevus (ocrelizumab), may result in shorter duration B-cell depleting effects in African American patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) than in white patients, a study suggests.

“While previous research has shown that this type of [into-the-vein] therapy is effective for people with those diseases, we also know that Black people tend to have more severe courses of MS,” llya Kister, MD, said in a press release. Kister, of the NYU Grossman School of Medicine in New York, is the study’s senior author and a fellow of the American Academy of Neurology.

“Our findings raise the question of whether the same therapy dose may be equally effective for all people, and that could have implications for the way Black people with autoimmune diseases like MS and neuromyelitis optica spectrum disorder are treated in the future,” Kister said.

The results were presented by Lucia Saidenberg, MD, the study’s first author, through an oral presentation at the Emerging Science Session of the 2021 virtual American Academy of Neurology Annual Meeting, running April 17–22.

The presentation was titled “African American patients with MS/NMOSD have more rapid B-cell repopulation than white patients following infusion of anti-CD20 B-cell depleting therapy.”

MS and NMOSD are two autoimmune diseases characterized by abnormal immune attacks against proteins of the nervous system, leading to neurodegeneration. One of the known players in these abnormal responses are immune B-cells, and are therefore considered good therapeutic targets.

B-cell targeting therapies, such as rituximab and Ocrevus, are “highly effective treatments,” for these conditions and “are known to cause a near complete depletion of B-cells in the blood soon after infusion,” Saidenberg said.

Of note, rituximab is used off-label in both patient populations, while Ocrevus is approved for the treatment of progressive and relapsing MS. Both therapies comprise antibodies that target the CD20 receptor found at the surface of B-cells and are administered directly into the bloodstream.

However, B-cell return after this type of treatment has not been well-studied in these patients, “particularly in African-American patients who are underrepresented in clinical trials for these drugs and tend to have more severe disease and faster disease progression compared to white patients with MS,” Sainderberg said.

As such, Kister and his team set out to assess how quickly B-cells came back in Black versus white patients after treatment with rituximab or Ocrevus.

They retrospectively analyzed the demographic, clinical, and lab data from 168 adults, 134 with MS and 32 with NMOSD, who had their B-cell numbers and subsets measured after at least one infusion of either of these therapies at the NYU MS Care Center.

Most (71%) patients were female; they had a mean age of 43.6 years. A total of 61 patients identified as African American and 60 as white. Most (68%) patients had been treated with rituximab, while one-third was given Ocrevus.

B-cell assessments were conducted at a mean interval of 6.6 months after treatment and up to more than 10 months.

Results showed that 50 (29.8%) patients had detectable B-cell repopulation after a median of 6.8 months following B-cell targeting therapy.

Specifically, none of the 40 patients with B-cell measurements within four months after treatment had detectable B-cells, while 18 (23%) of the 79 with available data between four and six months and 25 (61%) of the 41 with a six- to 12 month-assessment showed B-cell return.

This percentage increased progressively over time, with 90% of patients with B-cell measurement at more than 10 months after treatment showing detectable B-cells.

Notably, similar proportions of African American and white patients (20.8% vs. 17.9%) had B-cell return from four to six months following treatment.

However, at six to 12 months after treatment, “a significantly higher percentage of African American patients had B-cell repopulation, compared to White patients, 76% versus 33%,” Sainderberg said.

Moreover, the team found that most of the detected B-cells likely emerged from the bone marrow — where they are naturally produced — and that there were no differences in their subset ratios between African American and white patients showing B-cell return.

“We found that African-American patients with MS or [NMOSD] have faster B-cell repopulation following [anti-CD20 targeting therapies] compared to White patients, particularly at six to twelve months following infusion,” Sainderberg said.

“However, they had similar relative composition of B cell subsets in their repopulated samples,” she added.

“This may be clinically relevant for the timing of lab draws and [anti-CD20 therapy] dosing in African-American patients with MS or [NMOSD],” Sainderberg concluded.

One of the study’s limitations was that researchers retrospectively analyzed available B-cell assessments at different time points after treatment infusion, rather than prospectively conducting these measurements at the same specified times in all patients.

More research is needed to determine the clinical impact of this finding and whether faster return of B-cells in Black people means they are more likely to have poor treatment responses and more disease activity, the researchers noted.

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