Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma
(2022) In New England Journal of Medicine 386(26). p.2482-2494- Abstract
BACKGROUND Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end... (More)
BACKGROUND Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P=0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P=0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs.
(Less)
- author
- author collaboration
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- publishing date
- 2022-06-30
- type
- Contribution to journal
- publication status
- published
- subject
- in
- New England Journal of Medicine
- volume
- 386
- issue
- 26
- pages
- 13 pages
- publisher
- Massachusetts Medical Society
- external identifiers
-
- scopus:85132779020
- pmid:35657079
- ISSN
- 0028-4793
- DOI
- 10.1056/NEJMoa2201817
- language
- English
- LU publication?
- yes
- id
- 16b2edf4-cde8-4336-baa0-7faa798e513e
- date added to LUP
- 2022-10-24 15:43:38
- date last changed
- 2024-06-14 10:32:46
@article{16b2edf4-cde8-4336-baa0-7faa798e513e,
abstract = {{<p>BACKGROUND Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P=0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P=0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs.</p>}},
author = {{Wang, Michael L. and Jurczak, Wojciech and Jerkeman, Mats and Trotman, Judith and Zinzani, Pier L. and Belada, David and Boccomini, Carola and Flinn, Ian W. and Giri, Pratyush and Goy, Andre and Hamlin, Paul A. and Hermine, Olivier and Hernández-Rivas, José Ángel and Hong, Xiaonan and Kim, Seok Jin and Lewis, David and Mishima, Yuko and Özcan, Muhit and Perini, Guilherme F. and Pocock, Christopher and Song, Yuqin and Spurgeon, Stephen E. and Storring, John M. and Walewski, Jan and Zhu, Jun and Qin, Rui and Henninger, Todd and Deshpande, Sanjay and Howes, Angela and Le Gouill, Steven and Dreyling, Martin}},
issn = {{0028-4793}},
language = {{eng}},
month = {{06}},
number = {{26}},
pages = {{2482--2494}},
publisher = {{Massachusetts Medical Society}},
series = {{New England Journal of Medicine}},
title = {{Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma}},
url = {{http://dx.doi.org/10.1056/NEJMoa2201817}},
doi = {{10.1056/NEJMoa2201817}},
volume = {{386}},
year = {{2022}},
}