Use of Human Immunoglobulins in Secondary Immunodeficiencies Associated with Hematological Malignancy in Real-Life Practice: Which Patients, Which Treatment?

Introduction

Patients with hematologic malignancies suffer of frequent, severe, and potentially life-threatening infections. Secondary immune deficiency (SID) could be due to the disease and/or to its treatment (immunosuppressants, immunomodulators, monoclonal anti-CD20 antibodies, corticosteroids for auto-immune cytopenia). Polyvalent immunoglobulins (Ig) prevent infections by restoring serum Ig level. Ig may be administered intravenously (IVIG) or subcutaneously (SCIG), in hospital setting or at home with same clinical benefit but various constraints. According to the recommendations, it is legitimate to propose Ig replacement therapy for these patients if the residual Ig rate is less than 5 g/L and/or several infectious accidents occurred. These recommendations are old and based on scarce data (1980’s and 1990’s studies), meantime, new therapies and clinical protocols have been developed to treat hematologic malignancies. Recent data regarding the clinical profile of patients receiving substitutive Ig in France are still scarce.

Objective

The EPICURE study aims to describe the clinical profile of patients with hematologic malignancies and SID who start a substitutive treatment with Ig. Secondary objectives are to describe the modalities of treatment with Ig (route, place for administration and dosing) and physicians expectation to this treatment.

Patients and methods

Starting in 2011, EPICURE is an observational, prospective, longitudinal study involving 40 French centers. All adult SID patients with hematologic malignancies, receiving substitutive Ig may enter the study. To date, 240 patients have been included. We report the baseline data of the first 130 patients monitored.

Results

The analysis focused on 130 patients (88 men, 42 women), aged 67 ± 12 years, with myeloma (N=27), chronic lymphocytic leukemia (N=47), non-Hodgkin B lymphoma either aggressive (N=19) or indolent (N=21) or other hematologic malignancies (N=21). Ten patients (7.7%) presented also autoimmune cytopenia (AIC). 50 patients (38.5%) were receiving antineoplastic chemotherapy (N=47) and/or immunosuppressants (N=8). 34 patients (26.2 %) have received a bone marrow transplant. Serum IgG level was < 5g/L in 67.4% of patients who had no monoclonal peak. Auto-immune disease (apart from AIC) (N=4), renal failure (N=6) and diabetes (N=13) potentially increased the risk of infection. 119 patients (91.5%) had a history of infection within the last 12 months for a total of 236 infectious episodes. 66 (28.0%) of these episodes have been severe (OMS grading ≥ 3), 77 (32.6%) have led to hospitalization for a total number of 972 days, 136 (57.6%) have required oral antibiotics and 59 (25.0%) have required intravenous antibiotics. Replacement therapy with Ig was started as IVIG in 62 patients (47.7%) and as SCIG in 68 patients (52.3%). Treatment with Ig was started in hospital setting for almost all patients (IVIG 100%, SCIG 95.6%) and was planned to be pursued at home for 1.6% of patients with IVIG but 98.5% of patients with SCIG. Physicians were expecting to avoid further infections, to improve quality of life and to decrease hospitalization rate. Mean dosing was 436±257 mg/kg/month in line with current recommendations.

Conclusion

Patients with SID associated with hematologic malignancies who start a replacement therapy with Ig were at high risk of severe infections and most of them had a low serum level of Ig. Ig replacement therapy was started subcutaneously in half of patients for a further planned administration at home. The other half of patients received IVIG for a further planned administration in hospital setting. Longitudinal monitoring will describe physician’s satisfaction regarding replacement therapy, evaluate infection incidence rate over the treatment period and define therapeutic profiles for a better care of these patients.