Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study Journal Article
| Authors: | Cuneo, A.; Mato, A. R.; Rigolin, G. M.; Piciocchi, A.; Gentile, M.; Laurenti, L.; Allan, J. N.; Pagel, J. M.; Brander, D. M.; Hill, B. T.; Winter, A.; Lamanna, N.; Tam, C. S.; Jacobs, R.; Lansigan, F.; Barr, P. M.; Shadman, M.; Skarbnik, A. P.; Pu, J. J.; Sehgal, A. R.; Schuster, S. J.; Shah, N. N.; Ujjani, C. S.; Roeker, L.; Orlandi, E. M.; Billio, A.; Trentin, L.; Spacek, M.; Marchetti, M.; Tedeschi, A.; Ilariucci, F.; Gaidano, G.; Doubek, M.; Farina, L.; Molica, S.; Di Raimondo, F.; Coscia, M.; Mauro, F. R.; de la Serna, J.; Medina Perez, A.; Ferrarini, I.; Cimino, G.; Cavallari, M.; Cucci, R.; Vignetti, M.; Foà, R.; Ghia, P.; the GIMEMA; European Research Initiative (ERIC) on CLL; US study group |
| Article Title: | Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study |
| Abstract: | Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. |
| Keywords: | adult; aged; major clinical study; overall survival; neutropenia; advanced cancer; drug dose reduction; drug efficacy; rituximab; progression free survival; infection; bendamustine; retrospective study; protein p53; risk factor; febrile neutropenia; rash; comorbidity; aging; dermatitis; chronic lymphatic leukemia; cytopenia; creatinine clearance; chronic lymphocytic leukemia; tp53 gene; ibrutinib; very elderly; human; male; female; priority journal; article; mortality risk; real-world analysis; unfit patients |
| Journal Title: | Cancer Medicine |
| Volume: | 9 |
| Issue: | 22 |
| ISSN: | 2045-7634 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2020-11-01 |
| Start Page: | 8468 |
| End Page: | 8479 |
| Language: | English |
| DOI: | 10.1002/cam4.3470 |
| PUBMED: | 32969597 |
| PROVIDER: | scopus |
| PMCID: | PMC7666748 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
