Response to COVID-19 Infection and Vaccination in the CLL Population: A Large Single-Center Experience

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) are at increased risk of morbidity and mortality after infection with severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) and illness with coronavirus disease 2019 (COVID-19). Vaccination is of crucial importance in this patient population yet CLL patients demonstrate impaired vaccination responses with decreased ability to produce neutralizing anti-SARS-CoV-2 antibodies. COVID-19 boosters increase response rates in most patients with CLL, but their impact on "real-word” disease-related outcomes warrants further study. Therefore, we evaluated the outcomes of COVID-19 infection and response to COVID-19 vaccination and boosters in patients with CLL.

METHODS: This was a retrospective cohort study conducted in a single-center, North American academic teaching hospital in a large, urban area. Data was collected from January 2020 to December 2021. This time period coincided with SARS-CoV-2 Alpha and Delta variant predominant waves of infection in New York City, with Omicron (BA.1) dominating the last two weeks of December 2021. Patients with a diagnosis of CLL were evaluated for inclusion based on retrospective chart review. In total, 338 patients with CLL were included.

RESULTS: Of 338 patients with CLL, 252 patients (74.6%) underwent testing for COVID-19, of whom 57 (16.9%) had evidence of active or resolved infection. 10 patients tested positive by ECLIA, 38 by RT-PCR, and 9 by both detection methods. Characteristics of patients with documented infection are depicted in Figure 1A. 51 patients (89.5%) were symptomatic, and 6 (10.5%) were asymptomatic. 24 patients (42.1%) required hospitalization and 9 deaths were recorded (15.6% case fatality rate). 7 of 32 patients (21.8%) who had received CLL therapy died, versus 2 of 25 (8.0%) who never received therapy. Mortality was 19.6% in patients > 60 years compared to 0% in those ≤ 60 years.

269 patients were vaccinated against COVID-19, and 127 patients received a booster vaccination (third vaccine dose). The response rate in 114 evaluable patients who were tested for antibody response after 2 doses of vaccine was 66.6% (76/114, median assessment at 160 days [range, 1-253 days] after dose #2). 77 patients had antibody response evaluated only after receiving booster vaccination. In these patients, 70.1% had an antibody response at a median of 42 days (range, 5-145 days). In patients with both pre- and post-booster data (n=28), the response rate increased from 46.2% (13/28) to 85.7% (24/28) after receiving a third vaccination. Across the entire cohort, 74.3% (142/191) of evaluable patients responded to vaccination either on initial evaluation or on serial testing (Figure 1B-C).

11 COVID-19 infections occurred following at least one vaccination, and one patient died 2 days after receiving a second vaccination. Receipt of prior or current CLL-directed therapy differed between the antibody-positive and negative groups (53.5% vs 77.6%), although both groups had received a median of 2 lines of therapy. BTK inhibitors and combination venetoclax/anti-CD20 antibody were the most commonly used treatments in both groups. Median IgG (740 vs 504 mg/dL) and the proportion of patients with an IgG level < 700 mg/dL (43.0% vs 75.5%) differed between the antibody-positive and negative groups, respectively.

The case-fatality rate was 9.1% (1/11) in the vaccinated group compared to 17.8% (8/45) in the unvaccinated group. There were 6 documented COVID infections in patients who had a documented vaccination response and none in patients without documented response. No deaths occurred in the former group.

CONCLUSIONS: Serologic response to COVID-19 vaccination occurred in three-quarters of patients with CLL. This antibody response to vaccination compares very favorably to earlier, large studies that reported a response rate of 40-50%. A significant improvement in serologic response in patients between second and third vaccinations offers real-world evidence to support the efficacy of booster vaccination in this population. An additional expanded analysis including subsequent data from the Omicron variant predominant BA.1, BA.2, and BA.4/5 waves is in progress and will be presented.

Lipsky:AbbVie: Consultancy; AstraZeneca: Consultancy; Synthekine: Consultancy. Amengual:AstraZeneca: Consultancy; Daiichi Sankyo: Consultancy; Appia Pharmaceuticals: Research Funding. Heaney:CTI Pharma: Consultancy, Research Funding; BMS: Research Funding; Blueprint Medicines: Consultancy, Research Funding; Cogent Biosciences: Consultancy, Research Funding; Hoth Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Incyte Pharmaceuticals: Research Funding; Kartos Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; PhrmaEssentia: Consultancy; Sierra Oncology: Consultancy, Research Funding. Jurcic:Jazz Pharmaceuticals: Consultancy; Gilead/Forty Seven: Research Funding; Forma Theraputics: Research Funding; Celularity: Research Funding; Bristol Myer Squibb / Celgene: Consultancy, Research Funding; Arog: Research Funding; Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Syros Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lamanna:Oncternal: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Octapharma: Research Funding; Mingsight: Research Funding; Loxo Oncology/Eli Lilly and Company: Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZenenca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding.