Diminished Humoral and Cellular Responses to SARS-CoV-2 Vaccines in Patients with Chronic Lymphocytic Leukemia

Prior publications have demonstrated low rates of seroconversion to the SARS-CoV-2 mRNA vaccines in patients with chronic lymphocytic leukemia (CLL). In this national collaboration of 11 cancer centers around the United States, we aimed to further characterize and understand the vaccine-induced immune response, including T-cell responses and the impact of CLL therapeutics (NCT04852822). Eligible patients were enrolled into two cohorts: 1) at the time of the initial vaccination and 2) at the time of booster vaccination. Serologic response rates (anti-S) from the 210 patients in the initial vaccination cohort and 117 in the booster vaccination cohort were 56% (95% CI, 50-63%) and 68% (95% CI, 60-77%), respectively. Compared to patients not on therapy, those receiving B-cell-directed therapy were less likely to seroconvert (OR 0.27, 95% CI 0.15-0.49). Persistence of response was seen at 6 months;anti-S titers increased with administration of booster vaccinations. In the initial vaccination cohort, positive correlations were seen between quantitative serologic response and CD4 T-cell response for the Wuhan variant and to a lesser degree, for the Omicron variant (Spearman ρ = 0.45 for Wuhan, ρ = 0.25 for Omicron). In the booster vaccination cohort, positive correlations were seen between serologic response and CD4 T-cell responses for both variants (ρ = 0.58 Wuhan, ρ= 0.57 Omicron) and to a lesser degree for CD8 T-cell responses (ρ = 0.33 Wuhan, ρ = 0.22 Omicron). While no deaths from COVID-19 were reported after booster vaccinations, patients should use caution as newer variants emerge and escape vaccine-induced immunity.

Diminished Humoral and Cellular Responses to SARS-CoV-2 Vaccines in Patients with Chronic Lymphocytic Leukemia.

Prior publications have demonstrated low rates of seroconversion to the SARS-CoV-2 mRNA vaccines in patients with chronic lymphocytic leukemia (CLL). In this national collaboration of 11 cancer centers around the United States, we aimed to further characterize and understand the vaccine-induced immune response, including T-cell responses and the impact of CLL therapeutics (NCT04852822). Eligible patients were enrolled into two cohorts: 1) at the time of the initial vaccination and 2) at the time of booster vaccination. Serologic response rates (anti-S) from the 210 patients in the initial vaccination cohort and 117 in the booster vaccination cohort were 56% (95% CI, 50-63%) and 68% (95% CI, 60-77%), respectively. Compared to patients not on therapy, those receiving B-cell-directed therapy were less likely to seroconvert (OR 0.27, 95% CI 0.15-0.49). Persistence of response was seen at 6 months; anti-S titers increased with administration of booster vaccinations. In the initial vaccination cohort, positive correlations were seen between quantitative serologic response and CD4 T-cell response for the Wuhan variant and to a lesser degree, for the Omicron variant (Spearman P = 0.45 for Wuhan, P = 0.25 for Omicron). In the booster vaccination cohort, positive correlations were seen between serologic response and CD4 T-cell responses for both variants (P = 0.58 Wuhan, P = 0.57 Omicron) and to a lesser degree for CD8 T-cell responses (P = 0.33 Wuhan, P = 0.22 Omicron). While no deaths from COVID-19 were reported after booster vaccinations, patients should use caution as newer variants emerge and escape vaccine-induced immunity.

Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma.

BACKGROUND: Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS: We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS: Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = 0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS: Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs. (Funded by Janssen Research and Development and Pharmacyclics; SHINE ClinicalTrials.gov number, NCT01776840.).

Immunogenicity of Pfizer mRNA COVID-19 Vaccination Followed by J&J Adenovirus COVID-19 Vaccination in Two Patients with Chronic Lymphocytic Leukemia.

Individuals with chronic lymphocytic leukemia (CLL) have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role a heterologous boost would have in patients who did not respond to the initial two-dose mRNA vaccine series. SARS-CoV-2 specific immune responses, including antibodies and memory B-cells, CD4 and CD8 T-cells were assessed prior to vaccination, as well as postinitial vaccination series and post-third dose in two subjects. One subject seroconverted, had RBD-specific memory B-cells and spike-specific CD4 T-cells while the other did not. Both subjects had a spike-specific CD8 T-cell response after the original mRNA vaccination series that was further boosted after the third dose or remained stable. The results of this study, however small, are especially promising to CLL individuals who did not seroconvert following the initial mRNA vaccination series.