Presenting Author: Jordan Snyder, PharmD, BCOP, University of Kansas Health System, Kansas City, KS
BACKGROUND: Cytomegalovirus (CMV) reactivation is well described after allogeneic transplant and chimeric antigen receptor T-cell (CAR-T) therapies, but the implications are less well known in patients receiving bispecific antibodies (BsAbs). BsAbs have revolutionized the management of relapsed or refractory multiple myeloma (RRMM), but come with long-term adverse events, such as an increased risk for infections, including CMV.
OBJECTIVE: To evaluate the incidence of CMV reactivation in patients receiving BsAbs for RRMM.
METHODS: This multicenter, retrospective review included 555 patients who received teclistamab, elranatamab, or talquetamab. CMV reactivation was defined as any measurable CMV level. Descriptive statistics were utilized for patient and disease characteristics and for the rates of CMV reactivation. Logistic regression model was used to evaluate the risk factors for CMV reactivation.
RESULTS: In all, 308 (55%) patients received teclistamab, 36 (6%) received elranatamab, and 211 (38%) received talquetamab. The median age was 68 years (range, 32-89 years) and the median previous lines of therapy was 5 (range, 2-18), including 164 (30%) patients who received previous CAR-T. A total of 437 patients had CMV serostatus evaluated at some point during BsAb therapy, with 219 (50%) patients being CMV seropositive. Of the seropositive patients, 48 (22%) had CMV reactivation during BsAb treatment. CMV reactivation occurred in 8 (17%) patients who received dexamethasone treatment during step-up dosing, 6 (13%) patients who received tocilizumab treatment or prophylaxis, and 5 (10%) patients who received dexamethasone and tocilizumab during the step-up dose period. The median time to CMV reactivation was 1.2 months (range, 0-15.4 months) after treatment initiation. The median peak CMV was 289 IU/mL (range, 5-324,917 IU/mL). Of the 48 patients who had reactivation, 16 (33%) patients received CMV-directed therapy for a median duration of 24 days (range, 5-88 days). CMV disease occurred in 2 patients. One patient required hospitalization because of CMV reactivation, with hospitalization ongoing at time of data collection. No treatment discontinuations, interruptions, or deaths occurred from CMV. Age, the number of previous lines of therapy, previous BCMA-directed therapy, maximum-grade cytokine release syndrome, tocilizumab treatment, dexamethasone treatment, use of IVIG, and IgG levels at day 30 and day 90 were evaluated via logistic regression; none of the above factors predicted CMV reactivation.
CONCLUSION: CMV reactivation occurred in almost 25% of patients who are CMV seropositive and receiving bispecific antibodies for RRMM, with 33% of those patients requiring CMV-directed therapy. This incidence reflects the need for additional guidance for risk stratification, monitoring, and prophylactic strategies in this high-risk patient population.
- Noopur R, Anderson K, Einsele H, et al. Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel. Blood Cancer J. 2023;13:116.
- Pei C, Blackburn L, Sharma N, et al. Cytomegalovirus reactivation in patients with multiple myeloma treated with teclistamab: risk factors and clinical impact. Blood. 2024;144(suppl 1):4717.
- Mazahreh F, Mazahreh L, Schinke C, et al. Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis. Blood Adv. 2023;7:3069-3074.