Incidence of CMV-reactivation in multiple myeloma patients receiving bispecific antibodies

Abstract Introduction: Cytomegalovirus (CMV) reactivation is common following allogenic hematopoietic stem cell transplant and CAR T-cell therapy, but incidence in patients receiving T-cell directed therapies such as bispecific antibodies (bsAbs) is less well known. Use of bsAbs in relapsed/refractory multiple myeloma (RRMM) has increased over the past several years, however there is minimal guidance regarding monitoring or management of CMV in this patient population. This study aims to describe the incidence and risk factors of CMV reactivation in patients with RRMM receiving bsAbs. Methods: A multi-center, retrospective, chart review of 555 patients receiving teclistamab, elranatamab, and/or talquetamab for RRMM was conducted. All treatment was initiated prior to March 2025. ASTCT grading was used for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) grading. CMV serostatus and viral load were checked at the discretion of the treating prescriber. CMV reactivation was defined as any detectable CMV level. Descriptive statistics were utilized for patient and disease characteristics, and incidence of CMV reactivation. Logistic regression model was utilized to evaluate risk factors for CMV reactivation. Results: Of the 555 patients included in the analysis, 308 (55%) patients received teclistamab, 36 (6%) patients received elranatamab, and 211 (38%) patients received talquetamab. Median age of the entire patient population was 68 years (range: 32-89 years), 288 (51%) of patients were male and were predominately Caucasian (420, 76%) and African American (120, 22%). Median prior lines of therapy was 5 (range: 2-18). Intravenous immunoglobulin (IVIG) was administered in 356 (64%) patients and granulocyte colony-stimulating factor was utilized in 83 (15%) patients throughout treatment. Median IgG levels at 30 and 90 days post bsAbs initiation were 463 mg/dL (range: 21-10184 mg/dL) and 674 mg/dL (range: 18-8425 mg/dL), respectively. CRS occurred in 306 patients (55%) and was most commonly grade 1 (38%). ICANS occurred in 81 patients (14.6%), with grade 1 occurring in 39 patients (7%). Tocilizumab was required in 154 patients (27.7%), including 5 patients that received tocilizumab prophylaxis and dexamethasone was required in 160 patients (29%). One hundred and eighteen patients (21%) did not have serostatus checked or status was unknown and were excluded from the subsequent analysis. Two hundred nineteen of the remaining patients (50%) were CMV seropositive. Of patients who were CMV seropositive, 48 patients (22%) had CMV reactivation during treatment, 26 (12%) receiving teclistamab, 2 (0.9%) receiving elranatamab, and 20 (9%) receiving talquetamab. Median time to CMV reactivation was 1.2 months (range: 0-15.4 months) after treatment initiation. Median peak CMV was 289 IU/mL (range: 5-324917 IU/mL). Of the 48 patients that experienced reactivation, 16 patients (33%) received CMV-directed therapy for a median duration of 24 days (range: 5-88). CMV disease occurred in 2 patients, including one case each of disseminated skin and pneumonia, both occurring within the first two months of treatment. Neither patient had prior BCMA exposure or tocilizumab exposure. No treatment interruptions, treatment discontinuations, or deaths occurred due to CMV reactivation. On logistic regression, number of prior lines of therapy, prior BCMA-directed therapy, max CRS grade, tocilizumab treatment, dexamethasone treatment, use of IVIG, and IgG levels at day 30 and day 90 were nonsignificant for predicting CMV reactivation. Conclusion: In this retrospective study, 22% of patients experienced CMV reactivation with approximately a third of those patients requiring CMV-directed therapy. No baseline characteristics evaluated predicted CMV reactivation in patients with RRMM receiving a bsAbs. This incidence may reflect a potential need to provide routine monitoring for patients receiving bispecific antibodies, especially early in treatment. Further guidance on risk factors and thresholds for CMV treatment are necessary to ensure appropriate management of this high-risk patient population.