B Cell Depletion: The Latest Information on Disease Processes, Therapies

Dr. Hiepe

Depletion Strategies
Falk Hiepe, MD, a professor of medicine at the Charité University of Medicine, Berlin, Germany, concluded the session by describing two promising strategies to deplete long-lived plasma cells: proteosome inhibitors and anti-CD38 antibodies.

He suggested that proteosome inhibitors, such as bortezomib, would be able to effectively target plasma cells and explained how bortezomib treatment, while associated with fever and allergic skin reaction, was able to deplete plasma cells in refractory lupus.

He also highlighted results from a multicenter double-blind randomized controlled trial of bortezomib in refractory anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis and in other refractory antibody-mediated diseases that suggested the therapeutic effect of bortezomib is not only due to plasma cell depletion, but also blockade of nuclear factor kappa B (NF-κB). Dr. Hiepe cautioned that although these preliminary results are promising, use of the novel proteosome inhibitors remains limited by their toxicity.

All told, the new data have implications for the treatment of diseases mediated by B cells.

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

References

1. Radbruch A, Muehlinghaus G, Luger EO, et al. Competence and competition: The challenge of becoming a long-lived plasma cell. Nat Rev Immunol. 2006 Oct;6(10):741–750.
2. Bhoj VG, Arhontoulis D, Wertheim G, et al. Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood. 2016 Jul 21;128(3):360–370.