CLL-140 Booster and BTKi Interruption Improve Response to SARS-CoV-2 Vaccine in Patients With CLL

Introduction: Patients with chronic lymphocytic leukemia (CLL) have inadequate responses to vaccination, including SARS-CoV-2 mRNA vaccines. Treatment with anti-B-cell therapies, such as anti-CD20 monoclonal antibodies (mAb) and Bruton's tyrosine kinase inhibitors (BTKi), further suppress the antibody response to vaccines. Here, we aimed to evaluate clinical and laboratory parameters associated with vaccine response and the effect of BTKi interruption around the time of booster. Methods: A single-institution cohort study of patients with CLL was conducted at the National Institutes of Health. Treatment-naïve (TN) patients as well as those receiving treatment with a BTKi or venetoclax (VEN) were included. Patients who received IVIG, anti-SARS-CoV-2 mAb, or convalescent plasma within 3 months of vaccination were excluded. Anti-spike antibody titers were measured after completion of the primary series (two doses of Pfizer-BioNTech/Moderna vaccines or one dose of Janssen vaccine) and the first booster. Results: There were 86 patients in total (54 BTKi, 14 VEN, and 18 TN). The median age was 68.0, and 97.7% of patients received mRNA vaccine. After the primary series, seroconversion (anti-spike >0.8 U/mL) was detected in 53% of BTKi-treated patients, 43% of patients on single-agent VEN, and 67% of TN patients. After booster, seroconversion was detected in 87% of BTKi-treated patients, 50% of patients on single-agent VEN, and 83% of TN patients. Anti-spike antibodies increased after booster in 90% of patients who responded to the primary series. No patients who received anti-CD20 mAb within 12 months of vaccination (in combination with VEN) responded to the primary series or booster. Seroconversion was associated with higher serum IgM (P=0.023 after the primary series and P=0.039 after booster). Twelve patients interrupted BTKi for a median of 19 days (range 8–23) around the time of booster. Patients who interrupted BTKi had higher anti-spike antibodies (median 7,148 U/mL) than those who continued therapy (median 1,198 U/mL, P=0.018). Of the 12 patients who interrupted BTKi, 3 experienced lymph node pain and swelling and resumed BTKi earlier than intended. Conclusions: Increasing anti-spike antibodies with subsequent vaccinations support additional boosters in this population. BTKi interruption at the time of vaccination results in a more robust antibody response.