Real-World Experience of Infections with T-Cell Engagers in Multiple Myeloma and Non-Hodgkin’s Lymphoma

Introduction: T-cell Engagers (TCEs) offer new advances in the management of hematologic malignancies including multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). Since 2022, 6 TCEs have been approved for use in these two disease states. Despite its efficacy, a known adverse event to this drug class is an increased risk of infections. This study examines the incidence of infection and the impact on outcomes in patients treated with bispecific antibodies.

Methods: A retrospective chart review of 115 patients receiving TCEs for treatment of MM or NHL between 8/2022 and 4/2024 at the University of Kansas Health System was conducted. TCEs included in the analysis include: teclistamab, elranatamab, talquetamab, mosunetuzumab, epcoritamab, and glofitamab. Treatment held due to infection was defined as a treatment delay of > 2 weeks secondary to known or suspected infection. Overall response rate (ORR) was evaluated using the International Myeloma Working Group (IMWG) criteria or Lugano response criteria in MM and NHL, respectively. Descriptive statistics were used to summarize patient and disease characteristics, rates of infections, along with efficacy outcomes.

Results: Of the 115 patients, 60 (52%) had a diagnosis of MM, while 55 (48%) had a diagnosis of NHL. The median age was 70 years (range: 34-100 years), 86.1% were Caucasian, 67 (58.3%) were male, and median prior lines of therapy was 7 (range: 3-16) and 3 (range: 1-7) in MM and NHL, respectively. The most common subtype of MM and NHL was IgG Kappa (41.6%) and diffuse large B-cell lymphoma (56.4%), respectively. One hundred four patients (90.4%) received Herpes Simplex virus prophylaxis during treatment with TCE and 53 patients (46.1%) received Pneumocystis jiroveci pneumonia prophylaxis. Thirty-three (28.7%) and 22 (19.1%) patients received intravenous immunoglobulin (IVIG) and growth factor support, respectively. During treatment, 60 (52.2%) patients received additional corticosteroids for reasons other than pre-medication.

A total of 87 infections occurred; 27 (31%) known bacterial infections, 43 (49.4%) viral infections, 3 fungal (3.44%), and 14 (16.1%) unknown bacterial infection treated with empiric antibiotics. The most common type of infection that occurred were upper respiratory tract infections (40.2%), followed by pneumonia (16.1%), bacteremia (9.2%), and urinary tract infections (11.5%). The most frequently identified viruses were Rhinovirus/Enterovirus (42.9%) and COVID-19 (42.9%). Median time to first infection was 31 days (range:1-412). One or more infections occurred in 60 patients (52.2%) of the total patient population; 33 patients (55%) with MM and 27 patients (49.1%) with NHL developed one or more infection during the treatment period. Hospitalization due to infections occurred in 29 (25.2%) patients with a median length of stay of 6 days (range: 2-45 days). Cytomegalovirus (CMV) reactivation occurred in 16 patients (13.9%), with a median time to reactivation of 21 days (range: 0-363 days) from the initiation of treatment. Only 4 patients required treatment for CMV reactivation for a median duration of 21 days (range: 6-35 days).

Thirty-seven (32.2%) patients required treatment interruption due to infection or infectious symptoms. Only 24 (64.9%) patients resumed treatment following the interruption; the median duration of treatment interruption was 28 days (range: 14-112 days). The overall response rate was 62.1% in patients requiring treatment interruption, compared to 52.5% in those who did not require treatment interruption. Treatment discontinuation occurred in 89 patients (77.4%) with the most common reason being disease progression. The discontinuation rate due to infections or recurrent infections was 6.1%. Treatment-related mortality due to infection occurred in 6 patients (5.2%).

Conclusion: Infections are common among patients receiving TCEs – over 50% of patients in this cohort experienced infections with most patients infected with community acquired respiratory viruses. CMV reactivation occurred in nearly 15% of patients and justifies routine monitoring for CMV in these patients. Interestingly, treatment delays did not seem to affect response rates. Given the high incidence of infections, it is essential to explore additional strategies to reduce infection rates.