Baseline cytomegalovirus IgG levels predict reactivation in patients with multiple myeloma receiving elranatamab

Abstract Background: Elranatamab is a bispecific antibody approved for patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM). While effective, it is associated with treatment-related toxicities, including cytomegalovirus (CMV) reactivation. However, the incidence and risk factors for CMV reactivation in this setting remain undefined. Methods: We conducted a retrospective study of RRMM patients who initiated elranatamab therapy at the Japanese Red Cross Medical Center between June 2024 and July 2025. CMV seropositivity was defined as CMV immunoglobulin G (IgG) ≥6.0 AU/mL. CMV reactivation was defined as CMV DNA >500 copies/mL or ≥7 pp65-positive cells per 50,000 leukocytes when DNA testing was unavailable. Weekly CMV PCR monitoring was preferred but performed at the physician's discretion. Cumulative incidence was estimated using competing risks methodology. Baseline CMV IgG levels and other potential predictors of CMV reactivation were evaluated. Results: A total of 32 patients (median age, 65.5 years; 46.9% female) received elranatamab. Baseline CMV IgG titers were available for 27 patients (median, 166.1 AU/mL). The cumulative incidence of CMV reactivation was 26.5% at 3 months and 37.3% at 6 months. Preemptive valganciclovir was initiated upon reactivation. Among 13 patients with reactivation, 4 experienced recurrence after discontinuation of antiviral therapy, and 1 patient developed CMV retinitis, which was successfully treated with early antiviral intervention. Receiver operating characteristic analysis identified 88.7 AU/mL as the optimal baseline CMV IgG threshold for predicting reactivation. Patients with high baseline CMV IgG (≥88.7 AU/mL, n=19) had significantly higher cumulative incidence of reactivation at 3 and 6 months (42.2% and 57.9%) than those with low CMV IgG (<88.7 AU/mL, n=8; 9.1% at both time points; p=0.012). No significant differences were observed between the groups in monitoring frequency or duration, baseline characteristics, or the use of tocilizumab and corticosteroids for cytokine release syndrome (CRS). In the overall cohort, prior CAR-T therapy, corticosteroid or tocilizumab use, and prophylactic immunoglobulin were not significantly associated with reactivation risk. However, within the high IgG group, patients who received prophylactic immunoglobulin had a significantly lower 3-month cumulative incidence of reactivation compared to those who did not (27.3% vs. 100%, p<0.01). Conclusion: High baseline CMV IgG titers were associated with an increased risk of CMV reactivation following elranatamab therapy, consistent with findings in allogeneic transplantation and CAR-T cell therapy settings. Prophylactic immunoglobulin may help reduce reactivation risk in high-risk patients. Although limited by its single-center, retrospective design and small sample size, this study suggests that baseline CMV IgG titers may serve as a useful biomarker to guide risk-adapted CMV monitoring and prevention strategies during elranatamab treatment.