Study Characterizes Infections in Patients Treated With Bispecific Antibodies for Multiple Myeloma

Patients with multiple myeloma (MM) can be significantly impacted by infection, but clinical trial data related to infections during bispecific antibody (BsAb) therapy are limited. A study published in Blood Cancer Journal aimed to characterize the epidemiology and outcomes of infections in patients treated with BsAb therapy for MM.

BsAb therapy with multiple targets, such as BCMA, GPRC5D, and FCRH5, is becoming more common and has shown good rates of response for patients with MM. The incidence of infections of any grade has been reported at 13% to 76%, and the rate of grade 3 or higher infections has been reported at 3% to 45% in trials, the study authors noted—but diagnostic criteria and infection episodes have not been well described in prior research.

The new study aimed to characterize the epidemiology of infections and describe their outcomes to help improve antimicrobial prophylaxis and treatment strategies in patients with MM treated with BsAb therapy.

Electronic medical records from a total of 39 patients with MM who were treated with BsAb therapy between January 2018 and May 2022 were included in the retrospective study. The median (IQR) follow-up time was 152 (51-277) days. Most patients (97%) previously had hematopoietic stem cell transplant, and the median (IQR) number of prior therapy lines in the overall cohort was 6 (4-7). The median (IQR) patient age was 62 (56-70) years, and the majority of patients (62%) were male. The median (IQR) number of completed BsAb therapy cycles was 5 (2-11).

A total of 35 patients (90%) experienced at least 1 episode of infection (microbiologically defined [MDI], clinically defined [CDI], or fever of unknown focus [FUF]). Of those patients, 15 (38%) had an MDI. Grade 3 or higher infection episodes occurred in 16 (41%) of patients overall.

During the study period, 111 infection episodes occurred. Patients experienced infections at a median (IQR) of 2 (1-7) cycles of BsAb treatment. Of these episodes, 33 (30%) were MDI, 43 (39%) were CDI, and 35 (32%) were FUF. Among the MDI, 22 (58%) viruses, 15 (39%) bacteria, and 1 (3%) acid-fast bacilli were isolated. The respiratory system and gastrointestinal tract were the most common sites of infection.

A total of 63 episodes of infection led to hospital admission, and the median length of stay was 4 days. Four episodes (4%) led to intensive care admission. A median of 5 days of intravenous or oral antibiotics were required in patients who experienced infections.

The most common viral infections were rhinovirus/enterovirus, cytomegalovirus, and adenovirus (36%, 18%, and 18% of patients, respectively). Most bacterial infections were gastrointestinal (Salmonella sp., Escherichia coli, Pseudomonas aeruginosa, Clostridium difficile, Enterococcus faecalis), and there were no invasive fungal disease episodes recorded in the study.

In the 2 weeks prior to infection incidence, median (IQR) nadir neutrophil and lymphocyte counts were 1.8 (1.1-2.3) × 10⁹/L and 0.3 (0.1-0.7) × 10⁹/L, respectively. In 104 (94%) infection episodes, patients had received prophylactic valaciclovir; trimethoprim/sulfamethoxazole was administered in 104 cases (94%); and antifungal prophylaxis had been administered in 38 (34%) cases. Within 30 days prior to infection incidence, the median (IQR) cumulative prednisone-equivalent dose that patients received was 266.7 (106.7-266.7) mg.

Regarding other adverse events, 28 patients (72%) experienced cytokine release syndrome (CRS) and 2 (5%) experienced immune effector cell-associated neurotoxicity syndrome (ICANS). Median (IQR) neutropenia duration was 1 (0-3) day, and median (IQR) lymphopenia (<1.0 × 10⁹/L) duration was 22 (13-61) days in the study population. Further, 34 (87%) of patients experienced hypogammaglobulinemia, and 18 (53%) received immunoglobulin replacement.

“In this study of heterogenous BsAb platforms, incidence of any infection was comparable to current generation of therapies for relapsed disease including monoclonal antibody therapy with 90% of patients with median 6 lines of prior therapy experiencing at least 1 episode of infection,” the authors wrote. The rate of severe infections and the respiratory tract being a main site of infection were also in line with previous literature, they added.

Although the study cohort was small and the analysis was retrospective, the authors noted that this study was the first to fully describe infections in patients with MM treated with BsAb therapy.

“Infection remains a significant burden for MM patients treated with BsAb with severe infection rates of 41% and viral infections predominate,” the authors concluded. “Further studies are required in order to optimize prophylactic and preventative strategies.“

Reference

Sim BZ, Longhitano A, Er J, Harrison SJ, Slavin MA, The BW. Infectious complications of bispecific antibody therapy in patients with multiple myeloma. Blood Cancer J. Published online March 10, 2023. doi:10.1038/s41408-023-00808-8