Immunoglobulin substitution in patients with secondary antibody deficiency in chronic lymphocytic leukemia and multiple myeloma: a representative analysis of guideline adherence and infections

Abstract

Abstract Introduction In secondary immunodeficiency, immunoglobulin replacement therapy (IgRT) is recommended by guidelines (GL) for patients with IgG level < 4 g/l and more than 3 infections or a severe infection. IgRT may be appropriate if IgG level < 4 g/l and/or 1–3 less severe infections (≤ grade 2). Methods This was a retrospective sample analysis representative for practices and hospitals in Germany. The treatments and infection data were collected from patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). GL adherence (GLAD) was analyzed. Results Data from 1086 patients (CLL 490, MM 596) were collected from 86 centers. Of all patients, 34.8% developed IgG deficiency during therapy (CLL 35.5%; MM 34.2%). IgRT was given in 23.5% of CLL and 14.4% of MM patients. GLAD in hypogammaglobulinemia and indication to IgRT was 23.3% of 86 CLL and 22.1% of 77 MM patients. Without GLAD, the hazard ratio (HR) for any infection was 4.49 (95% CI 3.72–5.42; p < 0.001) and for severe infections (grade ≥ 3) 10.64 (95% CI 7.54–15.00; p < 0.001). Significant independent risk factors for infections were a higher Charlson Comorbidity Index, IgG deficiency, and 3rd + line treatment, as well as therapy with BTK inhibitors or chemotherapy in CLL. Multivariable analysis showed a significantly lower risk of severe infections after start of IgRT with a HR of 0.47 (95% CI 0.28–0.77; p = 0.003). Conclusions Guideline adherence correlated with fewer and less severe infections but was low in patients with indication to IgRT. Risk factors for infection can be identified. Risk of severe infections was significantly lower in patients with IgRT.