Risk factors for hypogammaglobulinemia in chronic lymphocytic leukemia patients treated with anti-CD20 monoclonal antibody-based therapies

Background: Hypogammaglobinemia is a well-recognized complication in chronic lymphocytic leukemia (CLL); however, the risk factors that lead to this complication after treatment with anti-CD20 monoclonal antibodies are not well understood. Methods: Using the Mayo Clinic CLL database, a retrospective chart review was conducted on patients enrolled between January 1995 and September 2017 who had pre- and post-treatment immunoglobulin values. The relationship between immunoglobulin values prior to treatment as well as post-treatment with clinical variables and overall survival (OS) was evaluated. Hypogammaglobinemia was defined as serum immunoglobulin G (IgG) levels <500 mg/dL and evaluated at both baseline and following treatment. Follow-up hypogammaglobinemia was treated as a time-dependent variable in Cox models. Results: A total of 179 patients met the eligibility criteria, 24 (13%) of whom had hypogammaglobinemia pre-treatment. Patients with hypogammaglobulinemia prior to treatment were more likely to have higher expression of CD49d (p value = 0.007). There was no difference in infection risk, other comorbidities, or OS between the pre- and post-treatment hypogammaglobinemia. In the subset of 155 subjects without hypogammaglobinemia at baseline, 22 developed hypogammaglobinemia. The median time to hypogammaglobinemia for these subjects was 36.6 months. Conclusion: Hypogammaglobinemia is commonly observed in CLL patients, at baseline as well as with the additional use of anti-CD20 therapies. The mean time to onset of hypogammaglobinemia after anti-CD20 therapies was 36 months. Time to hypogammaglobinemia does not significantly differ based on any of the CLL clinical factors studied. The presence of hypogammaglobinemia did not appear to impact survival or time to infection.