Background

Teclistamab, a BCMA x CD3 bispecific antibody, is a highly effective novel therapeutic option for patients with relapsed/refractory multiple myeloma (RRMM). Clinical trials like MajesTEC-1 show impressive efficacy but also high early infection rates, likely due to immune disruption from T-cell redirection and hypogammaglobulinemia. Real-world data are limited, especially in heavily pretreated, diverse patient populations. This study examines the incidence, timing, and risk factors of infection in a real-world RRMM cohort treated with teclistamab across a large academic health system.

Methods

We conducted a retrospective cohort analysis using the electronic medical record (EMR) database at Northwell Health. RRMM patients receiving ≥1 dose of teclistamab from October 2022 to April 2025 were included. Extracted data included demographics, disease characteristics, prior therapies, laboratory values (e.g., IgG levels), infection events (microbiologically or radiographically confirmed), and use of supportive interventions such as intravenous immunoglobulin (IVIG) and antimicrobial prophylaxis. We assessed time to first infection, overall infection rates, infection type (bacterial, viral, fungal), hospitalizations, and clinical predictors. Statistical analyses were conducted with Stata v.18.

Results

Among the 35 included patients, 19 (54.3%) were male, and 11 (30.6%) had high-risk cytogenetics. Median age was 59.5 years, median BMI was 26.5, and median time from diagnosis to teclistamab initiation was 2118 days. Cytokine release syndrome (CRS) occurred in 25 patients (71.4%), and immune effector cell-associated neurotoxicity syndrome (ICANS) in 5 patients (14.3%).

Grade 3 or more infections occurred in 19 of 35 patients (54.3%) during teclistamab therapy, requiring hospitalization, with a median time to first infection of 37 days. Despite universal antimicrobial prophylaxis, only 26 patients (74.3%) received documented IVIG prophylaxis. Among the 9 patients who didn't receive IVIG, 7 (77.8%) developed infection (median time: 26 days, IQR 11–369), compared to 8 of 26 (30.8%) patients who received IVIG (median time: 21 days, IQR 3–371). Infection rates were higher in patients without IVIG (77.8% vs. 46.2%), though not statistically significant (χ² = 2.69, p = 0.101). There was no significant difference in median IgG levels prior to hospitalization between patients who developed grade ≥3 infections (1,063 mg/dL; IQR: 242–3,360) and those who did not (647.5 mg/dL; IQR: 396.5–1,438.5) (p = 0.77).

Infection types varied: viral infections occurred in 4 patients, including COVID-19 (n=2), COVID-19 with RSV (n=1), and rhino/enterovirus with pneumococcal co-infection and CRS (n=1). One patient had disseminated cryptococcosis with concurrent rhino/enterovirus. Gram-negative bacteremia occurred in 9 patients, with pathogens including Klebsiella pneumoniae (n=2), Pseudomonas (n=1), Haemophilus influenzae (n=2), Enterobacter cloacae (n=2, one with septic shock), Escherichia coli (n=1), and Sphingomonas paucimobilis (n=1, with CRS). Gram-positive bacteremia occurred in 6 patients, including Enterococcus faecalis (n=2), MRSA (n=1), Streptococcus mitis/oralis (n=1), Streptococcus spp. (n=1, with CRS), and Listeria monocytogenes (n=1). One patient had fungal infection with Candida tropicalis.

At a median follow-up of 206 days, 12 of 35 patients (34%) had died, including 3 who died as inpatients during the initial teclistamab ramp-up dose. Median overall survival (OS) was not reached (NR) for the entire cohort. However, median OS was 42 days (95% CI, 29–69) among patients without IVIG prophylaxis, compared to NR in those who received IVIG (95% CI not estimable) (p=0.007).

Conclusion

In this real-world cohort of teclistamab-treated RRMM patients, infections were common, early, and often led to hospitalization. Lack of IVIG support appears to be associated with a higher infection rate, though not statistically significant due to limited sample. Shorter median OS without IVIG prophylaxis suggest a survival benefit with IVIG use.These findings underscore the need for early risk stratification, routine immunoglobulin monitoring, and the consideration of preemptive IVIG and antimicrobial prophylaxis. Larger prospective studies are warranted to validate these findings and guide clinical practice.

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2025
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