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Lancet. 2016 Feb 20;387(10020):770-8. doi: 10.1016/S0140-6736(15)00667-4. Epub 2015 Dec 7.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

Author information

1
Department of Medicine III, Klinikum der Universität München, Campus Grosshadern, Munich, Germany. Electronic address: Martin.Dreyling@med.uni-muenchen.de.
2
Department of Hematology, Jagiellonian University, Krakow, Poland.
3
Skånes Universitetssjukhus, Lund, Lund, Sweden.
4
Instituto De Ensino E Pesquisa São Lucas, São Paulo, Brazil.
5
Hematology Division, Hematology and Oncology Department, Niguarda Cancer Center, Niguarda Hospital, Milan, Italy.
6
Vseobecna fakultni nemocnice, Interni Klinika-Klinika Hematologie, Urologicka klinika, Prague, Czech Republic.
7
UZ Gent-Departement Oncologie, Gent, Belgium.
8
Instituto Biosanitario de Salamanca, Hospital Clinico Universitario Salamanca, Salamanca, Spain.
9
Champalimaud Centre for the Unknown, Hematology Department, Lisbon, Portugal; Instituto Português de Oncologia, Lisbon, Portugal.
10
Klinikum der Ruprechts-Karls-Universität Heidelberg-Med. Klinik u. Poliklinik V, Heidelberg, Germany.
11
University Medical School of the Johannes Gutenberg-University, Department of Hematology, Oncology and Pneumology, Mainz, Germany.
12
The Ottawa Hospital-General Campus, Ottawa-Hospital General Campus, Ottawa, Canada.
13
Seoul St Mary's Hospital, Seocho-gu, Seoul, South Korea.
14
Janssen Research & Development, LLC, Raritan, NJ, USA.
15
Janssen Research & Development, LLC, Spring House, PA, USA.
16
Janssen Research & Development, LLC, Leiden, The Netherlands.
17
Derriford Hospital, Plymouth, Devon, UK.

Erratum in

  • Lancet. 2016 Feb 20;387(10020):750.

Abstract

BACKGROUND:

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma.

METHODS:

This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74).

FINDINGS:

Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]).

INTERPRETATION:

Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma.

FUNDING:

Janssen Research & Development, LLC.

PMID:
26673811
DOI:
10.1016/S0140-6736(15)00667-4
[Indexed for MEDLINE]

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