Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib?
| Autor: | Claudia Baratè, Marta Coscia, Francesca Morelli, Paolo Sportoletti, Claudia Ielo, Chiara Cavalloni, Massimiliano Postorino, Annalisa Chiarenza, Alessandra Tedeschi, Marco Montillo, Roberto Cairoli, Alberto Fresa, Annalisa Biagi, Valentina Rossi, Giovanni Del Poeta, Roberta Murru, Stefania Ciolli, Giulia Zamprogna, Antonino Greco, Ramona Cassin, Anna Maria Frustaci, Angelo Curto Pelle, Francesco Di Raimondo, Gianfranco Lapietra, Luca Laurenti, Gianluigi Reda, Chiara Borella, Marzia Varettoni, Candida Vitale, Francesca Romana Mauro, Marina Deodato |
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| Přispěvatelé: | Tedeschi, A, Frustaci, A, Mauro, F, Chiarenza, A, Coscia, M, Ciolli, S, Reda, G, Laurenti, L, Varettoni, M, Murru, R, Barate, C, Sportoletti, P, Greco, A, Borella, C, Rossi, V, Deodato, M, Biagi, A, Zamprogna, G, Pelle, A, Lapietra, G, Vitale, C, Morelli, F, Cassin, R, Fresa, A, Cavalloni, C, Postorino, M, Ielo, C, Cairoli, R, Di Raimondo, F, Montillo, M, Del Poeta, G |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
drug safety medicine.medical_treatment retrospective study chemistry.chemical_compound Piperidines hemic and lymphatic diseases Prospective Studies event free survival Prospective cohort study progression free survival Lymphoid Neoplasia fitne Hematology aged comorbidity Cumulative Illness Rating Scale ECOG Performance Statu female Pharmaceutical Preparations risk factor Ibrutinib disease severity chronic lymphatic leukemia medicine.medical_specialty overall survival Neutropenia Article cancer chemotherapy male Internal medicine drug tolerance medicine Humans neutropenia human drug dose reduction neoplasms Retrospective Studies Chemotherapy business.industry Proportional hazards model Adenine aging medicine.disease Settore MED/15 Comorbidity Leukemia Lymphocytic Chronic B-Cell major clinical study predictor variable Clinical trial chemistry Concomitant treatment outcome business |
| Zdroj: | Blood Advances |
| Popis: | Key points Age per se does not influence outcome in CLL patients on ibrutinib, whereas CIRS score is predictive of treatment management, PFS, and EFS.ECOG-PS and neutropenia resulted as the only baseline parameters affecting overall survival. Visual Abstract Functional reserve of organs and systems is known to be relevant in predicting immunochemotherapy tolerance. Age and comorbidities, assessed by the cumulative illness rating scale (CIRS), have been used to address chemotherapy intensity. In the ibrutinib era, it is still unclear whether age, CIRS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) retain their predictive role on treatment vulnerability. In this series of 712 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia resulted as the most accurate predictors of treatment feasibility and outcomes. Age did not independently influence survival and ibrutinib tolerance, indicating that not age per se, but age-related conditions, may affect drug management. We confirmed the role of CIRS > 6 as a predictor of a poorer progression- and event-free survival (PFS, EFS). The presence of a severe comorbidity was significantly associated with permanent dose reductions (PDRs), not translating into worse outcomes. As expected, del(17p) and/or TP53mut and previous therapies affected PFS, EFS, and overall survival. No study so far has analyzed the influence of concomitant medications and CYP3A inhibitors with ibrutinib. In our series, these factors had no impact, although CYP3A4 inhibitors use correlated with Cox regression analysis, with an increased risk of PDR. Despite the limitation of its retrospective nature, this large study confirmed the role of ECOG-PS as the most accurate predictor of ibrutinib feasibility and outcomes, and importantly, neutropenia emerged as a relevant tool influencing patients’ vulnerability. Although CIRS > 6 retained a significant impact on PFS and EFS, its value should be confirmed by prospective studies. |
| Databáze: | OpenAIRE |
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