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The CD38-targeting antibody daratumumab has strong activity against multiple myeloma (MM), but is associated with a modest increase in infectious complications. Normal plasma cells (PC) are an important part of humoral immunity because they produce the majority of serum antibodies which contribute to the protection against a wide range of pathogens and toxins. The effect of daratumumab on normal PC is currently unknown. A better understanding of this is critical in order to provide recommendations on infectious prophylaxis, including vaccinations. Here, we show that daratumumab reduced the frequency of normal PC in bone marrow (BM) samples from patients with relapsed/refractory (RR) MM and that this was accompanied by reduced levels of polyclonal IgA, IgE and IgM. Polyclonal IgG levels remained unchanged, which may be explained by a subset of normal PC with reduced CD38 expression that survived during daratumumab therapy. In addition, daratumumab-

haematologica

Effect of daratumumab on normal plasma cells, polyclonal immunoglobulin levels, and vaccination responses in extensively pre-treated multiple myeloma patients