Cytomegalovirus reactivation in teclistamab-treated multiple myeloma patients: Clinical outcomes and risk factors

Abstract

Abstract Background: Teclistamab, a bispecific T-cell engager targeting BCMA, has demonstrated significant efficacy in relapsed/refractory multiple myeloma (MM) but is associated with profound immunosuppression. Cytomegalovirus (CMV) reactivation represents a potentially serious infectious complication, yet comprehensive data on incidence, risk factors, and clinical impact remain limited. Methods: We conducted a retrospective analysis of MM patients treated with teclistamab at University of Arkansas for Medical Sciences. All patients underwent systematic CMV monitoring with PCR testing as part of routine clinical care. We analyzed CMV reactivation incidence, timing, risk factors, treatment modifications, and clinical outcomes. CMV reactivation was defined as detectable CMV DNA >34.5 IU/ml. Results: Among 177 MM patients receiving Teclistamab (median age 63.8 years, 60.5% male, 78.5% White, 48% ECOG performance status 1), 35 patients (19.8%) had prior CMV reactivation before treatment initiation. Median time from diagnosis to first Teclistamab dose of 6.15 years (range 0.59-23.1 years). At treatment initiation, 85.9% of patients underwent baseline testing with negative CMV, and nine patients were concurrently receiving other immunosuppressants. During Teclistamab therapy, 38 patients (21.5%) developed CMV reactivation with a median initial positive level of 87.2 IU/ml (range 37.1-4,807.0) and median peak level of 288 IU/ml (range 45.3-20,000.0). Of those with reactivation, only 4 patients (10.5%) were symptomatic, 3 patients (7.9%) required antiviral treatment, and none developed end-organ damage. Eight patients (21.1%) experienced a second CMV viremia episode during continued Teclistamab treatment. Additional viral reactivations were observed including EBV (n=3), HHV-6 (n=2), parvovirus (n=7), and adenovirus (n=1). Patients with CMV reactivation demonstrated significant immunosuppression with median lowest laboratory values of hemoglobin 10.3 g/dl, WBC count 4.45 × 10³/µL, ANC 1.2 × 10³/µL, ALC 0.78 × 10³/µL, platelets 128 × 10³/µL, IgG 423 mg/dl, and functional IgG 325 mg/dl during reactivation episodes. Eight patients (21.1%) had elevated liver function tests during CMV reactivation. The median number of CMV tests performed before detection was 3 (range 0-11), and patients underwent a median of 4 CMV tests (range 0-44) throughout their treatment course. Univariable analysis identified age at diagnosis (p=0.005, OR 1.063) and prior CMV reactivation (p<0.001, OR 4.555) as significant predictors of CMV reactivation. Time to first Teclistamab dose was inversely associated with reactivation risk (p=0.010, OR 0.892). In multivariable analysis, prior CMV reactivation remained the strongest independent predictor (OR 3.34, p=0.005). Importantly, CMV reactivation did not impact overall survival (median 24.2 months, p=0.673), and no patients held or discontinued Teclistamab due to CMV reactivation. Conclusions: CMV reactivation occurs in approximately one-fifth of MM patients treated with Teclistamab, with prior CMV history being the primary risk factor. However, reactivation episodes are typically asymptomatic, rarely require treatment, and do not affect survival outcomes or necessitate therapy discontinuation. These findings suggest that while CMV monitoring during Teclistamab treatment may be clinically warranted, CMV reactivation should not be considered a significant barrier to continued therapy in most patients.