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

J 2020

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

CUNEO, A., A. R. MATO, G. M. RIGOLIN, A. PICIOCCHI, M. GENTILE et. al.

Basic information

Original name

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

Authors

CUNEO, A. (380 Italy, guarantor), A. R. MATO (840 United States of America), G. M. RIGOLIN (380 Italy), A. PICIOCCHI (380 Italy), M. GENTILE (380 Italy), L. LAURENTI (380 Italy), J. N. ALLAN (840 United States of America), J. M. PAGEL (840 United States of America), DM BRANDER (840 United States of America), B. T. HILL (840 United States of America), A. WINTER (840 United States of America), N. LAMANNA (840 United States of America), C. S. TAM (36 Australia), R. JACOBS (840 United States of America), F. LANSIGAN (840 United States of America), P. M. BARR (840 United States of America), M. SHADMAN (840 United States of America), A. P. SKARBNIK (840 United States of America), J. F. J. PU (840 United States of America), A. R. SEHGAL (840 United States of America), S. J. SCHUSTER (840 United States of America), N. I. N. SHAH (840 United States of America), C. S. UJJANI (840 United States of America), L. ROEKER (840 United States of America), E. M. ORLANDI (380 Italy), A. BILLIO (380 Italy), L. TRENTIN (380 Italy), M. SPACEK (203 Czech Republic), M. MARCHETTI (380 Italy), A. TEDESCHI (380 Italy), F. ILARIUCCI (380 Italy), G. GAIDANO (380 Italy), Michael DOUBEK (203 Czech Republic, belonging to the institution), L. FARINA (380 Italy), S. MOLICA (380 Italy), F. DI RAIMONDO (380 Italy), M. COSCIA (380 Italy), F. R. MAURO (380 Italy), J. DE LA SERNA (724 Spain), A. M. PEREZ (724 Spain), I. FERRARINI (380 Italy), G. CIMINO, M. CAVALLARI (380 Italy), R. CUCCI (380 Italy), M. VIGNETTI (380 Italy), R. FOA (380 Italy) and P. GHIA (380 Italy)

Edition

Cancer Medicine, Houston, John Wiley & Sons Ltd. 2020, 2045-7634

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.452

RIV identification code

RIV/00216224:14110/20:00116594

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/cam4.3470

UT WoS

000572155000001

Keywords in English

bendamustine; chronic lymphocytic leukemia; ibrutinib; real-world analysis; unfit patients

Abstract

V originále

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) 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.

Citovat

CUNEO, A., A. R. MATO, G. M. RIGOLIN, A. PICIOCCHI, M. GENTILE, L. LAURENTI, J. N. ALLAN, J. M. PAGEL, DM BRANDER, B. T. HILL, A. WINTER, N. LAMANNA, C. S. TAM, R. JACOBS, F. LANSIGAN, P. M. BARR, M. SHADMAN, A. P. SKARBNIK, J. F. J. PU, A. R. SEHGAL, S. J. SCHUSTER, N. I. N. SHAH, C. S. UJJANI, L. ROEKER, E. M. ORLANDI, A. BILLIO, L. TRENTIN, M. SPACEK, M. MARCHETTI, A. TEDESCHI, F. ILARIUCCI, G. GAIDANO, Michael DOUBEK, L. FARINA, S. MOLICA, F. DI RAIMONDO, M. COSCIA, F. R. MAURO, J. DE LA SERNA, A. M. PEREZ, I. FERRARINI, G. CIMINO, M. CAVALLARI, R. CUCCI, M. VIGNETTI, R. FOA and P. GHIA. 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. Cancer Medicine. Houston: John Wiley & Sons Ltd., 2020, vol. 9, No 22, p. 8468-8479. ISSN 2045-7634. Available from: https://dx.doi.org/10.1002/cam4.3470.

@article{1683656,
   author = {Cuneo, A. and Mato, A. R. and Rigolin, G. M. and Piciocchi, A. and Gentile, M. and Laurenti, L. and Allan, J. N. and Pagel, J. M. and Brander, DM and Hill, B. T. and Winter, A. and Lamanna, N. and Tam, C. S. and Jacobs, R. and Lansigan, F. and Barr, P. M. and Shadman, M. and Skarbnik, A. P. and Pu, J. F. J. and Sehgal, A. R. and Schuster, S. J. and Shah, N. I. N. and Ujjani, C. S. and Roeker, L. and Orlandi, E. M. and Billio, A. and Trentin, L. and Spacek, M. and Marchetti, M. and Tedeschi, A. and Ilariucci, F. and Gaidano, G. and Doubek, Michael and Farina, L. and Molica, S. and Di Raimondo, F. and Coscia, M. and Mauro, F. R. and de la Serna, J. and Perez, A. M. and Ferrarini, I. and Cimino, G. and Cavallari, M. and Cucci, R. and Vignetti, M. and Foa, R. and Ghia, P.},
   article_location = {Houston},
   article_number = {22},
   doi = {http://dx.doi.org/10.1002/cam4.3470},
   keywords = {bendamustine; chronic lymphocytic leukemia; ibrutinib; real-world analysis; unfit patients},
   language = {eng},
   issn = {2045-7634},
   journal = {Cancer Medicine},
   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},
   url = {https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.3470},
   volume = {9},
   year = {2020}
}

TY  - JOUR
ID  - 1683656
AU  - Cuneo, A. - Mato, A. R. - Rigolin, G. M. - Piciocchi, A. - Gentile, M. - Laurenti, L. - Allan, J. N. - Pagel, J. M. - Brander, DM - Hill, B. T. - Winter, A. - Lamanna, N. - Tam, C. S. - Jacobs, R. - Lansigan, F. - Barr, P. M. - Shadman, M. - Skarbnik, A. P. - Pu, J. F. J. - Sehgal, A. R. - Schuster, S. J. - Shah, N. I. N. - Ujjani, C. S. - Roeker, L. - Orlandi, E. M. - Billio, A. - Trentin, L. - Spacek, M. - Marchetti, M. - Tedeschi, A. - Ilariucci, F. - Gaidano, G. - Doubek, Michael - Farina, L. - Molica, S. - Di Raimondo, F. - Coscia, M. - Mauro, F. R. - de la Serna, J. - Perez, A. M. - Ferrarini, I. - Cimino, G. - Cavallari, M. - Cucci, R. - Vignetti, M. - Foa, R. - Ghia, P.
PY  - 2020
TI  - 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
JF  - Cancer Medicine
VL  - 9
IS  - 22
SP  - 8468-8479
EP  - 8468-8479
PB  - John Wiley & Sons Ltd.
SN  - 20457634
KW  - bendamustine
KW  - chronic lymphocytic leukemia
KW  - ibrutinib
KW  - real-world analysis
KW  - unfit patients
UR  - https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.3470
L2  - https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.3470
N2  - 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) 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.
ER  -

CUNEO, A., A. R. MATO, G. M. RIGOLIN, A. PICIOCCHI, M. GENTILE, L. LAURENTI, J. N. ALLAN, J. M. PAGEL, DM BRANDER, B. T. HILL, A. WINTER, N. LAMANNA, C. S. TAM, R. JACOBS, F. LANSIGAN, P. M. BARR, M. SHADMAN, A. P. SKARBNIK, J. F. J. PU, A. R. SEHGAL, S. J. SCHUSTER, N. I. N. SHAH, C. S. UJJANI, L. ROEKER, E. M. ORLANDI, A. BILLIO, L. TRENTIN, M. SPACEK, M. MARCHETTI, A. TEDESCHI, F. ILARIUCCI, G. GAIDANO, Michael DOUBEK, L. FARINA, S. MOLICA, F. DI RAIMONDO, M. COSCIA, F. R. MAURO, J. DE LA SERNA, A. M. PEREZ, I. FERRARINI, G. CIMINO, M. CAVALLARI, R. CUCCI, M. VIGNETTI, R. FOA and P. GHIA. 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. \textit{Cancer Medicine}. Houston: John Wiley \&{} Sons Ltd., 2020, vol.~9, No~22, p.~8468-8479. ISSN~2045-7634. Available from: https://dx.doi.org/10.1002/cam4.3470.

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