Secondary Hypogammaglobulinemia in Patients with Chronic Lymphocytic Leukemia Receiving Ibrutinib Therapy

• Published in: Indian journal of hematology & blood transfusion Vol. 38; no. 2; pp. 282 - 289
• Main Authors: Çelik, Serhat, Kaynar, Leylagül, Güven, Zeynep Tuğba, Baydar, Mustafa, Keklik, Muzaffer, Çetin, Mustafa, Ünal, Ali, Demirkan, Fatih
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.04.2022; Springer Nature B.V
• Subjects: Blood Transfusion Medicine; Case reports; Chemotherapy; Hematology; Human Genetics; Immunocompetence; Immunoglobulins; Inhibitor drugs; Leukemia; Medicine; Medicine & Public Health; Oncology; Original; Original Article; Side effects; Targeted cancer therapy; Bruton tyrozine kinase; Chronic lymphocytic leukemia; Hypogammaglobulinemia; Ibrutinib; Immunodeficiency
• ISSN: 0971-4502; 0974-0449; 0974-0449; 0971-4502
• DOI: 10.1007/s12288-021-01466-1

Secondary hypogammaglobulinemia (SHG) is characterized by a decrease in total serum immunoglobulin (Ig) levels and can lead to immunodeficiency associated with recurrent and severe infections and is a common complication of chronic lymphocytic leukaemia (CLL). SHG also increases with the treatment of CLL. Ibrutinib is one of these treatments and acts by inhibiting bruton tyrosine kinase. Twenty-seven patients with relapsed/refractory (R/R) CLL who received ibrutinib monotherapy were included. IgG levels, stage, bulky disease, previous treatments, genetics and laboratory features, overall survival (OS) and progression free survival (PFS) were compared with and without SHG. Nine patients (33.3%) had SHG and 18 patients (66.6%) didn’t have SHG. The mean IgG levels after ibrutinib treatment first, third, 6th and 12th months were 684, 531.3, 452 and 360 mg/dL respectively in SHG arm ( p  < 0.001) and 1156, 1058.2, 1012.8 and 886.9 mg/dL respectively in without SHG arm ( p  < 0.001). All patients with SHG had ibrutinib related other adverse effects(AEs) but 2 (11.1%) patients without SHG had AEs ( p  < 0.001). In SHG arm 7 (77.7%) had complete and partial remission but in other arm only 6 (33.3%) had ( p : 0.029). There was no significant difference in OS and PFS ( p values 0.95 and 0.64, respectively). IgG levels at the beginning of ibrutinib treatment is the best predicted value for SHG development in our study ( p  = 0.001). As a result, we reported a significant decrease in IgG values after ibrutinib monotherapy in R/R CLL patients. This decrease occurs every month after ibrutinib use, but after a maximum of 1 year.