Protective Role Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukemia: FOCUS on Subcutaneous Immunoglobulin Formulations

INTRODUCTION. Secondary antibody deficiency is a common complication in chronic lymphocytic leukemia (CLL) that could be present at diagnosis or can be acquired during the follow-up due to CLL progression, perturbation of non-neoplastic immune system and chemoimmunotherapy. Despite new and active target therapies a significant amount of CLL patients still develops severe and life-threatening infections. Intravenous immunoglobulin (IG) (IVIG) replacement therapy (IGRT) has been proven to be an effective supportive treatment in patients with primary and secondary antibody deficiency such as CLL. Subcutaneous immunoglobulin (SCIG) is a new valid treatment option that allows patients self-administration without access to the clinic which proved to be as effective as IVIG in primary immunodeficiencies. However, the activity SCIG is CLL patients with IG defect has been little investigated. The aim of this study was to retrospectively evaluate IG levels, infection rate and safety of patients treated with SCIG as compared to those managed with IVIG. METHODS. Inclusion criteria were: diagnosis of CLL according to iwCLL guideline, age >18 years, received at least 1 IVIG or SCIG infusion. IGRT was started according to hospital policies in patient with severe symptomatic hypogammaglobulinemia. The physician was responsible for the choice between IGRT formulations (the first patient received SCIG since Nov 2008). IG levels (IgG, IgA and IgM) were recorded within 3 months before starting IGRT (baseline), after 6 months and within three months from the last available follow-up. Continuous variables were compared with Wilcoxon's tests while categorical variables with Fisher's exact or Chi-square tests when appropriate. Time to IGRT discontinuation was calculated from the beginning IGRT to death or discontinuation (event) or last available follow-up /(censored). RESULTS. We gathered data from 116 CLL patients followed in 2 hematology centers who received IGRT: 63% were male, the median age at diagnosis was 58 years, 77 were at Binet A stage, 48% and 16% were unmutated IGHV and harbor TP53 abnormalities, respectively. 91% received at least one therapies, the median numbers of treatments were 3 (range 0-9) and 36% died during the follow-up due to infections in 22 cases, CLL progression in 5, Richter transformation in 6 patients and 9 other causes such as second cancers or major bleedings. Forty-nine patients received IVIG and 88 SCIG (41 the 20% formulation and 47 the 16% dr