Characterization of Hypogammaglobulinemia, Infection Incidence, and Mortality in Patients Receiving B-cell Maturation Antigen Chimeric Antigen Receptor (CAR) T-cell Therapy.

Chimeric antigen receptor T-cell therapy (CAR-T) targeting B-cell maturation antigen (BCMA) has emerged as a novel therapy demonstrating efficacy in the treatment of multiple myeloma. While previous research has shown many patients develop infections and hypogammaglobulinemia after therapy, there is a lack of data on the degree and clinical significance of these occurrences. We performed a retrospective evaluation of 147 patients receiving BCMA CAR-T for multiple myeloma in our large healthcare system. Demographics and hypogammaglobulinemia (immunoglobulin G [IgG] ≤600 mg/dL), categorized as mild (400 < IgG ≤ 600 mg/dL), moderate (200 < IgG ≤ 400 mg/dL), and severe (IgG ≤ 200 mg/dL), were evaluated. Risk factors for infections, mortality, and hypogammaglobulinemia pre- and post-CAR-T up to one year following treatment were estimated using odds ratio (OR), incidence ratio rate (IRR), and hazard ratio (HR) from Poisson regression. We identified 147 patients with multiple myeloma treated with BCMA CAR-T. The majority were male (56.5%) with a mean age 65.1 years (SD ± 9.2). Following CAR-T therapy, severe hypogammaglobulinemia was most prevalent (42%), followed by moderate (26%) and mild (12%) hypogammaglobulinemia. 44/147 (29.9%) patients developed a severe infection and 37/147 (25%) were hospitalized for infection. Prior to CAR-T therapy, 97/146 (69%) of patients had hypogammaglobulinemia (IgG ≤ 600 mg/dL), which increased to 117/145 (80%) after CAR-T. Additionally, 81/146 (55%) had moderate or severe hypogammaglobulinemia (IgG ≤ 400 mg/dL) pre-CAR-T, which increased to 99/145 (68%) post-CAR-T. Moderate to severe hypogammaglobulinemia was present <3 months post-CAR-T in 66/106 (62%) and persisted for >12 months in 99/145 (68%). Hypogammaglobulinemia pre-CAR-T therapy was associated with increased risk of hypogammaglobulinemia (adjusted OR: 16.07; 95% CI: 2.21-117.02; P < .006) and infection (adjusted IRR: 2.02; 95% CI = 1.06-3.83; P = .03) after therapy. Lower IgG levels (adjusted HR: 1.26; 95% CI = 1.13-1.41; P = .0001) and larger differences between pre- and post-CAR-T IgG level (adjusted HR: 1.40; 95% CI = 1.21-1.61; P < .0001) were associated with an increased risk of mortality. Severe infections and persistent hypogammaglobulinemia lasting over one year were common following BCMA CAR-T. Hypogammaglobulinemia was a risk factor associated with infection and mortality.