Multinational retrospective study of association of antibiotic-associated dysbiosis with bispecific antibody outcomes in multiple myeloma

The gut microbiota plays a critical role in regulating immune homeostasis and modulating responses to cancer immunotherapies. A retrospective study at six European and North American centers evaluated the association between prior exposure to broad-spectrum antibiotic within 30 days before initiation of CD3-engaging bispecific antibodies (BsAbs) and outcomes in patients with relapsed or refractory multiple myeloma (R/R MM). The study included 237 adult R/R MM patients. Three months after initiating BsAb treatment, the best overall response rate was 73%, with a complete response rate of 47%; the 1-year overall survival (OS) probability was 74% (95% CI 68-81) and 1-year progression-free survival probability was 49% (43-56). Prior exposur to antibiotics (n=179) was associated with worse OS and PFS. In multivariable analyses, antibiotic exposure remained independently associated with poorer outcomes. The authors conclude that antibiotic-induced dysbiosis prior to BsAb therapy was associated with inferior outcomes in R/R MM.