Hypogammaglobulinemia, Infections, and Mortality in Patients Treated with Blinatumomab

Introduction Blinatumomab, a bispecific antibody targeting CD3 and CD19, utilizes a unique mechanism of action to selectively engage cytotoxic T cells and CD19-positive B cells, resulting in direct lysis of tumor cells and exerting antileukemia effect. Hypogammaglobulinemia and infectious complications post-blinatumomab are reported but not well characterized. Methods We performed a retrospective evaluation of 208 patients at a single center receiving blinatumomab therapy and evaluated demographics, hypogammaglobulinemia (IgG ≤ 600 mg/dL), and infections prior to and after blinatumomab therapy, and risk factors for hypogammaglobulinemia, infection, hospitalizations, and mortality. Incidence rates and risk for infections were calculated using Poisson regression. Risk factors for mortality were calculated using Cox proportional hazards regression. Results We identified 208 patients who had received blinatumomab (mean age 49.7 years [range 3-84], 54.3% male). Of the patients with IgG evaluated, 51/101 (50.5%) had hypogammaglobulinemia pre-blinatumomab therapy, which increased to 108/119 (90.8%) post-blinatumomab therapy. Mean IgG levels decreased from 640 mg/dL to 375 mg/dL pre- to post-blinatumomab (p < 0.0001). 50% of patients developed a serious infection post-blinatumomab therapy, with 15.6% of patients developing a serious infection within the first 30 days after blinatumomab initiation. Risk factors for hypogammaglobulinemia included younger age and hypogammaglobulinemia pre-blinatumomab therapy (hazard ratio [HR] 1.90; 95% CI 1.09-3.29; p = 0.023). When adjusted for age, sex, ANC/ALC, and prior stem cell transplant, risk factors for infection after blinatumomab included male sex and hypogammaglobulinemia pre-blinatumomab (adjusted IRR 1.57; 95% CI 1.15-2.15; p = 0.005). Risk factors for mortality after blinatumomab included age ≤ 18 years, hypogammaglobulinemia pre-blinatumomab (adjusted HR 2.35; 95% CI 1.15-4.82; p = 0.02), and severe infections (particularly in the first 30 days of therapy) (adjusted HR 5.44; 95% CI 2.41-12.25; p ≤ 0.0001). Conclusion Hypogammaglobulinemia and infection are common with blinatumomab therapy and may be higher than previously reported. Pre-blinatumomab hypogammaglobulinemia was associated with an increased risk of hypogammaglobulinemia, infection, and mortality post-therapy. Further research is needed to understand the role of immunoglobulin replacement given the frequency of hypogammaglobulinemia observed.