TY - JOUR
T1 - Rethinking the feasibility and safety of venetoclaxobinutuzumab in chronic lymphocytic leukemia
T2 - nontraditional factors may play a role in clinical practice
AU - Frustaci, Anna Maria
AU - Galitzia, Andrea
AU - Lucignano, Mariano
AU - Appio, Lorena
AU - Olivieri, Jacopo
AU - Sanna, Alessandro
AU - Baraté, Claudia
AU - Pane, Fabrizio
AU - Schiattone, Luana
AU - Casadei, Beatrice
AU - Ferrarini, Isacco
AU - Figuera, Amalia
AU - Sportoletti, Paolo
AU - Loseto, Giacomo
AU - Stelitano, Caterina
AU - Visentin, Andrea
AU - Celli, Melania
AU - Mauro, Francesca Romana
AU - Palombi, Massimiliano
AU - Coscia, Marta
AU - Innao, Vanessa
AU - Moia, Riccardo
AU - Motta, Marina
AU - Russo, Filomena
AU - Tani, Monica
AU - Arcari, Annalisa
AU - Boccellato, Elia
AU - Borella, Chiara
AU - Capochiani, Enrico
AU - Ferrari, Angela
AU - Gentile, Massimo
AU - Giachetti, Roberta
AU - Giordano, Annamaria
AU - Bullo, Martina
AU - Lista, Enrico
AU - Malandruccolo, Luigi
AU - Musso, Maurizio
AU - Varettoni, Marzia
AU - Vozella, Federico
AU - Cibien, Francesca
AU - Merli, Michele
AU - Nocilli, Laura
AU - Pasquini, Maria Cristina
AU - Romeo, Azzurra Anna
AU - Rossi, Valentina
AU - Turri, Gloria
AU - Vanazzi, Anna
AU - Cavaliere, Marina
AU - Gozzetti, Alessandro
AU - Crucitti, Lara
AU - Lucesole, Moira
AU - Deodato, Marina
AU - Tomasso, Annamaria
AU - Zappaterra, Arianna
AU - Murru, Roberta
AU - Patti, Caterina
AU - Laurenti, Luca
AU - Tedeschi, Alessandra
PY - 2026/1/1
Y1 - 2026/1/1
N2 - The concept of fitness to receive treatment with novel agents in chronic lymphocytic leukemia (CLL) remains debated. Comorbidities and treatment-related logistics are increasingly recognized as key factors in treatment feasibility. Venetoclax- obinutuzumab (VO) has demonstrated efficacy in both fit and unfit patients in clinical trials, yet real-world data remain limited. This retrospective, multicenter study analyzed disease- and patient-related factors affecting VO management and outcomes in 271 patients. Fitness was assessed using comorbidity indices (CLL-CI, CIRS, CCI), Eastern Cooperative Oncology Group performance status, and caregiver need. Adverse events (AE) and treatment modifications were evaluated across four treatment phases. The median age of the patients was 66 years (19% ≥75 years old); 83% had comorbidities, 34% required polypharmacy, and 10% needed caregiver support. Overall, 96% completed debulking, 89% the full regimen, while 11% discontinued due to toxicity (Tox-DTD). Grade ≥3 AE occurred in 55%, tumor lysis syndrome in 6%, severe infusion-related reactions in 5%. Overall, 3.3% of the patients died during treatment. Unfit patients did not show a significantly higher risk of treatment modifications due to AE. Dose adjustments were more frequent during debulking. None of the validated fitness scores predicted treatment feasibility or Tox-DTD. Global feasibility was impacted by age (P=0.002), prior malignancies (P=0.003), prolonged steroid pre-treatment (P<0.001), and baseline thrombocytopenia (P=0.013). Tox-DTD correlated with caregiver need (P=0.029), endocrine comorbidities (P=0.025), prior malignancies (P=0.002), hypogammaglobulinemia (P=0.003), high lymphocyte count (P=0.034), and prolonged steroid pre-treatment (P=0.006). In conclusion, this study confirms the feasibility of VO treatment in CLL clinical practice, highlighting the role of traditionally overlooked factors that ultimately do have an impact.
AB - The concept of fitness to receive treatment with novel agents in chronic lymphocytic leukemia (CLL) remains debated. Comorbidities and treatment-related logistics are increasingly recognized as key factors in treatment feasibility. Venetoclax- obinutuzumab (VO) has demonstrated efficacy in both fit and unfit patients in clinical trials, yet real-world data remain limited. This retrospective, multicenter study analyzed disease- and patient-related factors affecting VO management and outcomes in 271 patients. Fitness was assessed using comorbidity indices (CLL-CI, CIRS, CCI), Eastern Cooperative Oncology Group performance status, and caregiver need. Adverse events (AE) and treatment modifications were evaluated across four treatment phases. The median age of the patients was 66 years (19% ≥75 years old); 83% had comorbidities, 34% required polypharmacy, and 10% needed caregiver support. Overall, 96% completed debulking, 89% the full regimen, while 11% discontinued due to toxicity (Tox-DTD). Grade ≥3 AE occurred in 55%, tumor lysis syndrome in 6%, severe infusion-related reactions in 5%. Overall, 3.3% of the patients died during treatment. Unfit patients did not show a significantly higher risk of treatment modifications due to AE. Dose adjustments were more frequent during debulking. None of the validated fitness scores predicted treatment feasibility or Tox-DTD. Global feasibility was impacted by age (P=0.002), prior malignancies (P=0.003), prolonged steroid pre-treatment (P<0.001), and baseline thrombocytopenia (P=0.013). Tox-DTD correlated with caregiver need (P=0.029), endocrine comorbidities (P=0.025), prior malignancies (P=0.002), hypogammaglobulinemia (P=0.003), high lymphocyte count (P=0.034), and prolonged steroid pre-treatment (P=0.006). In conclusion, this study confirms the feasibility of VO treatment in CLL clinical practice, highlighting the role of traditionally overlooked factors that ultimately do have an impact.
KW - Humans
KW - Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy
KW - Aged
KW - Male
KW - Female
KW - Bridged Bicyclo Compounds, Heterocyclic/adverse effects
KW - Middle Aged
KW - Retrospective Studies
KW - Aged, 80 and over
KW - Sulfonamides/adverse effects
KW - Feasibility Studies
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Antibodies, Monoclonal, Humanized/adverse effects
KW - Adult
KW - Treatment Outcome
U2 - 10.3324/haematol.2025.287799
DO - 10.3324/haematol.2025.287799
M3 - Original Article
C2 - 40568727
SN - 0390-6078
VL - 111
SP - 206
EP - 218
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
IS - 1
ER -