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

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.

An updated perspective on immunoglobulin replacement in chronic lymphocytic leukaemia in the era of targeted therapies

“…There is little evidence in relation to the role of IgRT in persons with CLL treated with BTKi or inhibitors of BCL-2. The results of a recent, large, retrospective study suggests that adherence to IgRT guidelines positively correlates with fewer and less severe infections ( 6 ). This finding corroborates the results of a recent European expert conference on recommendations for the diagnosis and treatment of antibody deficiency with IgRT in patients with malignant hematologic diseases ( 56 ) This consensus document supports the initiation of IgRT in persons with IgG of less than 4g/L and at least one major infection treated with parenteral antibiotics or three infections over a twelve month period.…”

“…Such patients with a monoclonal component had shortened survival, irrespective of age, with biclonal paraproteins associated with the shortest survival outcomes (38). IgRT in the era of targeted agents: More evidence is needed It is generally agreed that persons with CLL with significant hypogammaglobulinemia characterized by an IgG of less than 4g/L, in the presence of recurrent or severe bacterial infection despite antibiotic prophylaxis, are candidates for long-term IgRT (6). IgRT is usually administered at replacement doses of 0.2-0.4g/kg per month (39).…”

“…It is generally agreed that persons with CLL with significant hypogammaglobulinemia characterized by an IgG of less than 4g/L, in the presence of recurrent or severe bacterial infection despite antibiotic prophylaxis, are candidates for long-term IgRT ( 6 ). IgRT is usually administered at replacement doses of 0.2-0.4g/kg per month ( 39 ).…”

“…Current guidelines recommend immunoglobulin replacement therapy (IgRT) to reduce the risk of bacterial infections and hospitalization in patients with recurrent severe infections and low immunoglobulin G (IgG) levels ( 6 ). In addition, there is evidence that IgRT with polyvalent human IgG has immunomodulatory effects on the innate immune system, whilst the effect of such therapy on B-cell function appears to be more complex and poorly defined ( 7 ).…”

Increased Access to Immunoglobulin Replacement Therapy for Patients with Primary Immunodeficiency in Poland Based on Clinical Usage Data of Immunoglobulin G over a 5-Year Period

“…In our opinion, this is an area that needs improvement. The implementation of a registry and audit of compliance would help assess the needs and tools for treatment efficacy in patients with SID [ 26 ]. In addition to drug programs, immunoglobulins were used for weak, off-label indications and indications where the benefit of IgG treatment is doubtful or unclear.…”