RESUMEN
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.
RESUMEN
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.
RESUMEN
Patients with relapsed warm antibody autoimmune hemolytic anemia (wAIHA) have limited treatment options. Fostamatinib is a potent, orally administered spleen tyrosine kinase inhibitor approved in the United States and Europe for the treatment of adults with chronic immune thrombocytopenia (ITP). This phase 2 study evaluated the response to fostamatinib, administered at 150 mg BID orally with or without food in adults with wAIHA and active hemolysis with hemoglobin (Hgb) <10 g/dL who had failed at least one prior treatment. Hemoglobin levels and safety assessments were performed at visits every 2 weeks. The primary endpoint was Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by week 24 without rescue therapy or red blood cell transfusion. Eleven of 24 (46%) patients achieved the primary endpoint. Increases in median Hgb were detected at week 2 and sustained over time. Median lactate dehydrogenase levels and reticulocyte counts generally declined over time with little change in median haptoglobin levels. The most common adverse events (AEs) were diarrhea (42%), fatigue (42%), hypertension (27%), dizziness (27%), and insomnia (23%). AEs were manageable and consistent with the fostamatinib safety database of over 3900 patients across multiple diseases (rheumatoid arthritis, B-cell lymphoma, COVID-19, and ITP). No new safety signals were detected. Fostamatinib may be a promising therapeutic option for wAIHA. A randomized, double-blind, phase 3 study is nearing completion.