Cytomegalovirus seropositivity is associated with improved responses to CD38 monoclonal antibody therapies in multiple myeloma: A single-centre retrospective study

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.