Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study
Language English Country England, Great Britain Media print-electronic
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
26673811
DOI
10.1016/s0140-6736(15)00667-4
PII: S0140-6736(15)00667-4
Knihovny.cz E-resources
- MeSH
- Adenine analogs & derivatives MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphoma, Mantle-Cell drug therapy pathology MeSH
- Piperidines MeSH
- Antineoplastic Agents adverse effects therapeutic use MeSH
- Pyrazoles adverse effects therapeutic use MeSH
- Pyrimidines adverse effects therapeutic use MeSH
- Recurrence MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sirolimus adverse effects analogs & derivatives therapeutic use MeSH
- Neoplasm Staging MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Adenine MeSH
- ibrutinib MeSH Browser
- Piperidines MeSH
- Antineoplastic Agents MeSH
- Pyrazoles MeSH
- Pyrimidines MeSH
- Sirolimus MeSH
- temsirolimus MeSH Browser
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.
Department of Hematology Jagiellonian University Krakow Poland
Department of Medicine 3 Klinikum der Universität München Campus Grosshadern Munich Germany
Derriford Hospital Plymouth Devon UK
Instituto Biosanitario de Salamanca Hospital Clinico Universitario Salamanca Salamanca Spain
Instituto De Ensino E Pesquisa São Lucas São Paulo Brazil
Janssen Research and Development LLC Leiden The Netherlands
Janssen Research and Development LLC Raritan NJ USA
Janssen Research and Development LLC Spring House PA USA
Klinikum der Ruprechts Karls Universität Heidelberg Med Klinik u Poliklinik 5 Heidelberg Germany
Seoul St Mary's Hospital Seocho gu Seoul South Korea
Skånes Universitetssjukhus Lund Lund Sweden
The Ottawa Hospital General Campus Ottawa Hospital General Campus Ottawa Canada
References provided by Crossref.org
Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas
Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma
International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017)
