Abstract Background: Patients with hematologic malignancies are at significantly higher risk for severe COVID-19 due to disease-related and treatment-induced immunosuppression. Despite widespread vaccine availability, many patients fail to mount effective immune responses. Additionally, vaccine uptake rates have plummeted, exacerbating the risk faced by this vulnerable population. On March 22, 2024, the FDA issued Emergency Use Authorization for pemivibart (Pemgarda™), a long-acting monoclonal antibody for pre-exposure prophylaxis in individuals with moderate-to-severe immunocompromise. While initial approval was based on laboratory and pharmacokinetic data, real-world evidence on Pemivibart's safety and effectiveness in high-risk populations remains limited. This study evaluates adverse reactions and breakthrough infections following Pemivibart use in immunocompromised patients with hematologic malignancies. Methods: We analyzed 166 adult patients with lymphoid malignancies who received Pemivibart between March 2024 and July 2025 after obtaining appropriate IRB approvals. Clinical data included age, sex, vaccine history, adverse reactions, and incidence of COVID-19 infection after Pemivibart. COVID-19 infection was confirmed through antigen or PCR testing. Descriptive statistics summarized the cohort. Results: All patients had lymphoid malignancies (CLL, n=102 (61.4% of the cohort)) at various disease and treatment course points, and had received at least one Pemivibart dose. The mean age was 69.7 years; 36.1% were female. The average number of prior COVID-19 vaccine doses was 4.04, and 58 patients (34.9%) received two or more Pemivibart doses. Median follow-up was 203 days. Adverse reactions occurred in 4.2% (7/166), including grade 3 anaphylaxis in 1 (0.9%) patient that resolved with supportive care, and grade 2 infusion-related reactions in 2 (1.8%) patients, all of which responded well to supportive care. Eight patients (4.8%) developed COVID-19 after Pemivibart administration, corresponding to an incidence rate of 7.2 breakthrough COVID-19 infections per 1000 patient-months. Of these, none resulted in hospitalization, ICU admission, or death. All eight patients experienced mild COVID-19 infections per IDSA guidelines, and six patients (75%) had received prior COVID-19 vaccination. Conclusion:Pemivibart was well-tolerated in immunocompromised patients with lymphoid malignancies, with a low incidence of adverse reactions and breakthrough infections. No patients on Pemivibart were hospitalized, highlighting the continued importance of layered COVID-19 prevention strategies. Additionally, our observed incidence rate of breakthrough infection was comparable to or superior to that of immunocompromised patients receiving vaccination alone. These real-world findings support using Pemivibart as an adjunct to vaccination in high-risk populations and underscore the need for pre-exposure prophylaxis, especially in patients with a compromised ability to generate adequate vaccine-mediated immunity. Detailed data will be provided at the conference.
Sunderraj et al. (Mon,) studied this question.