Infection risk factors and burden in patients treated with T-cell engaging bispecific antibodies for relapsed B-cell lymphoma and multiple myeloma

Abstract

Abstract Background T-cell engaging bispecific antibodies (BsAbs) are increasingly utilized in patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). Although high response rates have been reported, infections were common on initial trials with these agents. Clinically significant infections (≥ grade 3) were reported in >10% of patients receiving CD20-targeting BsAbs for NHL and as many as 40-50% of those receiving BCMA-targeted BsAbs for MM. We sought to describe the incidence, characteristics, and risk factors associated with infections in patients receiving BsAbs. Methods We collected baseline, treatment and outcome information from our institutional databases, identifying patients with r/r NHL or MM treated with a BsAb as a single-agent between 2020–2024. To determine factors associated with incidence of infection, Wilcoxon rank sum test was used on numerical variables, and Fisher's exact test or Pearson's Chi-squared test for categorical variables. All tests were performed as two-tailed tests, with p < 0.05 considered statistically significant. Results We identified 200 patients, 56 (28%) NHL and 144 (72%) had MM. 113 (57%) had one or more infections during the treatment period or following BsAb discontinuation (90 days from last dose or until initiation of next line of therapy). Of these, 55 (49%) had 1 infection, 32 (28%) had 2 distinct infections and 26 (23%) had 3 or more. Of the total of 197 individual infection events, 21 (11%) led to death, 16 (8%) were grade 4, 66 (33%) were grade 3, and 94 (48%) were grade 1-2. Fifty percent of infections were confirmed or presumed based on clinical presentation and diagnostic evaluation to be bacterial, 37% viral, 8% fungal (excluding PJP) and 1% PJP, while the etiology was unknown in 4% of cases. A causal organism was identified in 127 (64%) of cases and the most common organisms were SARS-CoV-2 (16 cases; 8%), E. coli (13; 7%), Influenza (10; 5%), K. pneumoniae (9; 5%), Rhinovirus/Enterovirus (9; 5%), CMV (7; 4%), P. aeruginosa (8; 4%), C. difficile (6; 3%), Parainfluenza (6; 3%), RSV (4; 2%), MRSE (3; 2%), E. faecium (3; 2%), E. faecalis (3; 2%); Aspergillus sp. (3; 2%) and P. jirovecii (2; 1%). The incidence of grade≥ 3 infections varied among patients treated with different BsAbs (p<0.05): odronextamab (4/6, 67%), elranatamab (10/25, 40%), epcoritamab (13/34, 38%) teclistamab (22/81, 27%), talquetamab (6/38, 16%), mosunetuzumab (2/14, 14%). No grade 3 or higher infections were reported with glofitamab (0/2). Antiviral prophylaxis was prescribed in 189 (95%) of patients, and anti-PJP in 180 (90%), while anti-fungal and antibacterial prophylaxis were prescribed in 5 (2.5%) and 12 (6%), respectively. Prophylactic intravenous IVIG was prescribed in 85 (43%) cases. Receipt of IVIG was associated with decreased incidence of grade ≥ 3 infections (19% vs. 35%, p<0.05). Patients who experienced ICANS were more likely to have a grade ≥ 3 infection, 46% vs. 26% (p<0.05). The occurrence of CRS did not predispose to higher grade ≥ 3 infection risk (p=0.8) and neither did administration of tocilizumab (p=0.5). Patients who developed grade ≥ 3 infections had lower albumin (p<0.05) and higher LDH levels (p<0.05) at baseline. Baseline neutropenia was not related to incidence of infection (p=0.4), neither was development of severe neutropenia (ANC<0.5) while on BsAb (p=0.08). Although patients who developed any infection had longer time to resolution of neutropenia (median 34 vs. 22.5 days, p<0.05). Conclusions In our patient cohort, infection rates were higher than in trials for those diagnosed with NHL, while rates were lower for patients treated with teclistamab. This could reflect the use of prophylaxis as well as the deeper immunosuppressive effect of prior lines of therapy in NHL patients. The correlation of ICANS with infection risk is important, likely a result of steroid therapy and should prompt close observation of patients experiencing this complication. Our results highlight the effect of IVIG, and this measure should be considered in hypogammaglobulinemic patients. While non-bacterial infection prophylaxis was common, half of the infections were presumed or demonstrated to be bacterial, and prospective evaluation of antibacterial prophylaxis should be considered for high-risk patients.