LAUSR

The CD38‐targeting monoclonal antibodies (CD38 mAbs) are well‐established therapies in multiple myeloma (MM), but responses to treatment are not always deep or durable. Natural killer (NK) cells deficient in Fc epsilon receptor gamma subunits, known as g‐NK cells, are found in higher numbers among individuals exposed to cytomegalovirus (CMV) and are able to potentiate the efficacy of daratumumab in vivo. Here, we present a single‐centre, retrospective analysis of 136 patients with MM with known CMV serostatus who received a regimen containing a CD38 mAb (93.4% daratumumab and 6.6% isatuximab). CMV seropositivity was associated with an increased overall response rate to treatment regimens containing a CD38 mAb (odds ratio 2.65, 95% confidence interval [CI] 1.17–6.02). However, CMV serostatus was associated with shorter time to treatment failure in a multivariate Cox model (7.8 vs. 8.8 months in the CMV‐seropositive vs. CMV‐seronegative groups respectively, log‐rank p = 0.18, hazard ratio 1.98, 95% CI 1.25–3.12). Our data suggest that CMV seropositivity may predict better response to CD38 mAbs, although this did not correspond to longer time to treatment failure. Larger studies directly quantitating g‐NK cells are required to fully understand their effect on CD38 mAb efficacy in MM.