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Simple Summary: We prospectively analyzed COVID-19 morbidity and severity in 200 consecutive patients with CLL. Increased COVID-19 morbidity was observed in vaccinated patients with CLL. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19. Most patients, 36.5%, experienced COVID-19 during the Omicron pandemic, 26% of patients were hospitalized, and 4% died. Moreover, 10% had re-infections. In multivariate analysis of elderly patients, TP53 disrupted, heavily pre-treated, and those in early treatment with targeted agents showed increased vulnerability to COVID-19. Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in patients with CLL. High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients. [ABSTRACT FROM AUTHOR]

Intrahospital COVID-19 infection outbreak management: Keep calm and carry on Patients who could not be discharged, were transferred to COVID units or COVID-free departments, based on the NPS result. Seven of nineteen infected patients deceased: in two, death occurred due to the disease progression in presence of asymptomatic/paucisymptomatic COVID-19; in five patients (26.3%) instead, COVID-19 was considered as the main reason of death. [Extracted from the article]

RS mutation profile was tested on pre-treatment cell free DNA. Rate of unmeasurable MRD and impact of mutations and chronic lymphocytic leukemia-RS clonal relation on outcomes will be presented at the meeting. B Introduction: b Chemoimmunotherapy is the standard first line treatment of diffuse large B-cell lymphoma (DLBCL) variant of Richter syndrome (RS). [Extracted from the article]

P110-γ and -δ act in lymphocytes chemotaxis, presenting distinct, nonredundant roles in B- and T-cell migration and adhesion to stromal cells. Moreover, phosphoinositide-3-kinase-γ inhibition contributes to regulate macrophage polarization inhibiting cancer growth. Duvelisib (IPI-145) is an oral first-in-class, dual phosphoinositide-3-kinase inhibitor targeting p110-δ/γ exerting its activity in preclinical studies across different prognostic groups. In a large Phase III study, duvelisib showed superior progression-free survival and overall response rate compared with ofatumumab, thus leading to its approval for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Immune-related effects are the main reason for treatment suspension, thus affecting survival benefit. Nevertheless, the correct management of adverse events, eventually including dose modification, allows patients to remain on treatment. In conclusion, duvelisib represents a promising treatment in chronic lymphocytic leukemia and a salvage therapy after ibrutinib. [ABSTRACT FROM AUTHOR]