Clinical Lymphoma, Myeloma & Leukemia, Vol.22, Suppl.2 - October 2022

S83 E XABS-181-C LL I n fectio n Prophylaxis i n Chro n ic L y m phocytic L euke m ia Clare Su n , M D 1, * 1 Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA *Correspo n di n g author: clare.sun@nih.gov Keywords chronic lymphocytic leukemia, supportive care, vaccinations, immunoglobulin replacement, prophylaxis Introduction Supportive therapy is an important aspect in the management of chronic lymphocytic leukemia (CLL). CLL is characterized by profound and widespread immune dysfunction affecting both adaptive and innate immunity. These immune defects contribute to infections, second primary neoplasms, and autoimmune cytopenias. While most patients achieve long-term disease control with standard targeted therapy, they remain immunocompromised. As treatment options continue to improve, the morbidity and mortality associated with immune dysregulation may eventually outweigh that caused directly by CLL. Herein, I will discuss available therapies to bolster immunity in patients with CLL. Vaccinations Patients with CLL should follow an immunization schedule for immunocompromised people. Due to an increased risk of infection, vaccines may be administered to patients with CLL outside of routine age-based recommendations. 1 Despite these efforts, the immune response, and thus efficacy, of vaccines are impaired in CLL. Treatment targeting B cells, such as anti- CD20 monoclonal antibodies (mAb) and Bruton tyrosine kinase inhibitors (BTKi), further suppress antibody responses to vaccination. In general, the de novo immune response to vaccination against novel antigen (e.g., hepatitis B virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) is weaker than the amnestic response to recall antigen (e.g., varicella zoster virus). Two concurrent clinical trials of recombinant hepatitis B vaccine (HepB- CpG) and recombinant zoster vaccine (RZV) in CLL reported an antibody response rate to HepB-CpG of 28.1% in treatment naïve (TN) patients and 3.8% in BTKi-treated patients compared to an antibody response rate to RZV of 7 8.8% in TN patients and 40% in BTKi-treated patients. 2 The cellular response to RZV was also suppressed in patients on a BTKi. 3 An impaired antibody response to SARS-CoV-2 vaccination in CLL patients, worsened by treatment with BTKi or venetoclax in combination with anti- CD20 mAb, has been consistently observed. 4,5 Immunizations should be completed when patients with CLL are in active surveillance. An exception is live attenuated vaccines, which carry a risk of viral replication and infection and are contraindicated in patients with CLL. 6 For patients on treatment, vaccine deferral should be considered based on the specific type of treatment and its inhibitory effect on vaccine response. For example, the antibody response to vaccine is virtually absent within 12 months of anti-CD20 mAb therapy. In contrast, vaccine deferral is impractical in patients on a BTKi due to the continuous nature of treatment. Furthermore, the effect of BTKi on vaccine response is less uniform than anti-CD20 mAb therapy and varies between vaccine types. Passive Immunization Hypogammaglobulinemia is a progressive phenomenon in CLL and increases susceptibility to infections. 7 Patients with a serum IgG <4 g/L and a history of recurrent bacterial infections requiring systemic antibiotics should be considered for immunoglobulin replacement therapy (IgRT). 8 IgRT reduces the incidence and severity of bacterial infections, but does not affect viral or fungal infections. 8,9 The starting dose of IgRT is 400 mg/kg every 3 weeks until IgG is at steady state (approximately 10 weeks or 3 infusions) followed by a maintenance dose of 400 mg/kg every 5 weeks. 9 The dose can be titrated upward in patients with breakthrough infections. 10 Although most patients in the United States receive IgRT intravenously, subcutaneous injections have demonstrated higher IgG trough levels, fewer infections, and better tolerability. 11 Other forms of passive immunization during the coronavirus pandemic are anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma. Due to an inadequate antibody response to vaccination, patients with CLL should receive pre-exposure prophylaxis with anti-SAR-CoV-2 mAb, but cautioned about weakened activity against Omicron and likely future variants. 12,13 When antiviral therapies are unavailable, treatment with anti- SARS-CoV-2 mAb or convalescent plasma may be appropriate. Prophylactic Antimicrobials Despite altered immunity related to disease, prophylactic antimicrobials are generally reserved for patients with CLL on active treatment. The risk of infection, and hence the need for prophylaxis, depends on the type of treatment. Opportunistic infections such as herpes zoster and Pneumocystis jirovecci