Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.

4th Department of Internal Medicine Haematology Faculty of Medicine in Hradec Králové University Hospital and Charles University Prague Hradec Kralove Czech Republic

Amsterdam UMC Amsterdam The Netherlands

AO S Croce e Carle Cuneo Italy

Center of Immunology Department Stefan S Nicolau Institute of Virology Bucharest Romania

Central European Institute of Technology Masaryk University Brno Czech Republic

Centre for Research and Technology Hellas Thessaloniki Greece

Colentina Clinical Hospital Bucharest Romania

Department of Medicine Faculty of Medicine and Health Örebro University Örebro Sweden

Department of Medicine Faculty of Medicine Kuwait University Safat Kuwait

Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece

Hospital de la Santa Creu 1 Sant Pau Josep Carreras Leukaemia Research Institute Barcelona Spain

IRCCS San Raffaele Hospital Milan Italy

Laboratory Medicine Service IRCCS San Raffaele Hospital Milano Italy

Medical University of Lublin Lublin Poland

St Antonius Hospital Nieuwegein The Netherlands

Tel Aviv Sourasky Medical Center Tel Aviv Israel

Tel Aviv University Tel Aviv Israel

Turin University Turin Italy

University Emergency Hospital Bucharest Romania

University Hospital Brno Brno Czech Republic

University of Medicine and Pharmacy Carol Davila Bucharest Romania

Vita Salute San Raffaele University Milan Italy

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Realizing precision medicine in chronic lymphocytic leukemia: Remaining challenges and potential opportunities