Real-World Incidence of Infections in BCMA-Targeting Bi-Specific Antibodies in Relapsed/Refractory Multiple Myeloma

Introduction: B-cell maturation antigen (BCMA) targeting bispecific antibodies (BsAbs) are highly effective in relapsed/refractory multiple myeloma (RRMM). Complications of BCMA BsAbs include cytopenias and an increased risk of infections including upper respiratory infections and pneumonia. Currently, there are 2 BCMA BsAbs available, teclistamab and elranatamab, with more in development. While these complications are known, there is no standardized practice surrounding the infection risk and incidence associated with treatment. Therefore, optimal management of these infections should be evaluated.

Methods: A retrospective review of 84 patients with RRMM who received teclistamab or elranatamab from August 2022 through May 2024 at the University of Kansas Medical Center or Levine Cancer Institute was conducted. High-risk cytogenetics were defined as: t(4;14), t(14;16), t(14;20), del17p, 1q12 gain, 1p del. Frequencies and proportions were used to summarize categorical outcomes while descriptive statistics were used to summarize continuous factors. Kaplan Meier methods were used to estimate median time to first infection. Data cutoff was 7/1/2024.

Results: Of the 84 patients included, 77 patients received teclistamab and 7 received elranatamab. The median age was 69 years (range 32-87), 46 (54.8%) were males, and 12 (14.3%) were Black. Forty-eight patients (57.1%) had IgG immunophenotype and 49 patients (60.5%) had high risk cytogenetics. The median duration of treatment with BsAbs was 3 months (range 0.03-17 months) and 33 (39.3%) had a change in dose frequency during treatment. As of data cutoff, 27 patients remained on treatment. To reduce the risk of infectious complications, 84 (100%) and 52 (61.9%) patients received herpes zoster and Pneumocystis jiroveci pneumonia (PJP) prophylaxis, respectively. Fifty-one patients (60.7%) experienced hypogammaglobulinemia. Of those, 34 patients received intravenous or subcutaneous immune globulin therapy while receiving BsAbs. Grade 4 neutropenia occurred in 16 (19.1%) patients and growth factor support was administered in 11 (68.8%) of these patients.

Among the 84 patients, 47 patients (56%) experienced at least 1 infection of any grade; grade 3 or higher infections occurred in 16 patients (19.1%). Seventeen patients (20.2%) experienced more than one infection while on treatment. Median time to first infection was 3.2 months (95% CI 1.9-5.1). Over a third of patients (36.9%) experienced infections during the first 3 months of therapy. Additionally, 23 patients (27.4%) had at least one pneumonia infection. Thirty-two patients (38.1%) experienced a treatment hold due to an infectious complication. Among the 70 total infections experienced by patients, the most common were bacterial (50%) and viral (47.1%). Most infections (65.7%) occurred prior to a change in the weekly dosing schedule.

Thirty-eight patients (45.2%) receiving teclistamab or elranatamab experienced an unplanned hospital admission during therapy with 11 (13.1%) patients experiencing multiple hospitalizations. Infection was the primary cause of admission for 27 (32.1%) patients in our cohort. Among the 49 total hospitalizations experienced by patients, median length of stay for an infection was 5 days (range 1-25). Four hospitalizations (11.4%) involved ICU-level care for an infectious complication.

Conclusion: This study illustrates the high rate of infections that occur in patients receiving BCMA-targeted BsAbs with over half of patients experiencing at least one infection. Rates of infections occurred in this study at similar rates to previously published studies; infections occurred in 76.4% and 69.9% in MajesTEC-1 and MagnetisMM-3, respectively. With most patients experiencing infections early in treatment, while receiving weekly dosing, there may be an argument to reducing treatment frequency earlier than 6 months that is currently recommended in the package insert. Additional strategies, such as standardized antimicrobial prophylaxis and/or decreased dose frequency, are needed to further reduce the longer-term infection risk.

Mahmoudjafari:Janssen: Consultancy; Sanofi: Consultancy. Ahmed:Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.