Prospective Study of Cytomegalovirus Reactivation in Patients With Multiple Myeloma Receiving Anti-CD38 and BCMA...

Cytomegalovirus (CMV) is an opportunistic pathogen that causes infection in certain immunocompromised hosts, but the risk of clinically significant CMV infection in patients with multiple myeloma (MM) is not well understood.

We conducted a prospective observational study of CMV reactivation in CMV seropositive patients with MM who were receiving anti-CD38 and B-cell maturation antigen (BCMA) targeted therapies to characterize the rate of viral reactivation and clinically significant infection. We monitored CMV PCR biweekly for 12 weeks in patients with newly diagnosed and relapsed MM receiving these agents. The primary endpoint was CMVPCR ≥500 IU/mL; secondary endpoints included any detectable CMV viremia, CMV end-organ disease, and overall survival. An Anderson-Gill Cox model for recurrent events was used to model detectable CMV viremia at each visit, and a swimmer plot was used to present biweekly follow-up data for patients with CMV detection.

We included 40 patients, including 15 patients with newly diagnosed MM and 25 patients with relapsed MM. Three participants (7.5%) developed CMV viremia ≥ 500 IU/mL during follow-up, and 24 additional patients had CMV detection below that threshold. One patient received preemptive treatment with valganciclovir for asymptomatic viremia, but there was no symptomatic CMV infection, end-organ disease or mortality during study follow-up. In multivariate analysis, lagged lymphopenia (low absolute lymphocyte count at preceding visit), prior CMV infection, relapsed disease (compared to newly diagnosed MM), and younger age were associated with a higher risk of CMV detection.

Low-level CMV detection occurs frequently in patients with MM receiving agents targeting CD38 and BCMA, but viremia is usually self-limited, and in our study cohort, there was no symptomatic CMV infection despite relatively high rates of CMV detection.