Academic Journal
Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: a phase 1/2 trial of the European MCL network (SAKK 36/13).
| العنوان: | Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: a phase 1/2 trial of the European MCL network (SAKK 36/13). |
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| المؤلفون: | Novak, U., Fehr, M., Schär, S., Dreyling, M., Schmidt, C., Derenzini, E., Zander, T., Hess, G., Mey, U., Ferrero, S., Mach, N., Boccomini, C., Böttcher, S., Voegeli, M., Cairoli, A., Ivanova, V.S., Menter, T., Dirnhofer, S., Scheibe, B., Gadient, S., Eckhardt, K., Zucca, E., Driessen, C., Renner, C. |
| المصدر: | EClinicalMedicine, vol. 64, pp. 102221 |
| سنة النشر: | 2023 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Bortezomib, High risk biology, Ibrutinib, Mantle cell lymphoma |
| الوصف: | The Bruton's tyrosine kinase inhibitor ibrutinib and the proteasome inhibitor bortezomib have single-agent activity, non-overlapping toxicities, and regulatory approval in mantle cell lymphoma (MCL). In vitro, their combination provides synergistic cytotoxicity. In this investigator-initiated phase 1/2 trial, we established the recommended phase 2 dose of ibrutinib in combination with bortezomib, and assessed its efficacy in patients with relapsed or refractory MCL. In this phase 1/2 study open in 15 sites in Switzerland, Germany and Italy, patients with relapsed or refractory MCL after ≤2 lines of chemotherapy and both ibrutinib-naïve and bortezomib-naïve received six cycles of ibrutinibb and bortezomib, followed by ibrutinib maintenance. For the phase 1 study, a standard 3 + 3 dose escalation design was used to determine the recommended phase 2 dose of ibrutinib in combination with bortezomib. The primary endpoint in phase 1 was the dose limiting toxicities in cycle 1. The phase 2 study was an open-label, single-arm trial with a Simon's two-stage min-max design, with a primary endpoint of overall response rate (ORR) assessed by CT/MRI. This study was registered with ClinicalTrials.gov, NCT02356458. Between August 2015 and September 2016, nine patients were treated in the phase 1 study, and 49 patients were treated between November 2016 and March 2020 in the phase 2 of the trial. The ORR was 81.8% (90% CI 71.1, 89.8%, CR(u) 21.8%) which increased with continued ibrutinib (median 10.6 months) to 87.3%, (CR(u) 41.8%). 75.6% of patients had at least one high-risk feature (Ki-67 > 30%, blastoid or pleomorphic variant, p53 overexpression, TP53 mutations and/or deletions). In these patients, ibrutinib and bortezomib were also effective with an ORR of 74%, increasing to 82% during maintenance. With a median follow-up of 25.4 months, the median duration of response was 22.7, and the median PFS was 18.6 months. PFS reached 30.8 and 32.9 months for patients with a CR or Cru, respectively. The combination of ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37781158; info:eu-repo/semantics/altIdentifier/eissn/2589-5370; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_B8178ECC6BDA2; https://serval.unil.ch/notice/serval:BIB_B8178ECC6BDA; https://serval.unil.ch/resource/serval:BIB_B8178ECC6BDA.P001/REF.pdf |
| DOI: | 10.1016/j.eclinm.2023.102221 |
| الاتاحة: | https://serval.unil.ch/notice/serval:BIB_B8178ECC6BDA https://doi.org/10.1016/j.eclinm.2023.102221 https://serval.unil.ch/resource/serval:BIB_B8178ECC6BDA.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_B8178ECC6BDA2 |
| Rights: | info:eu-repo/semantics/openAccess ; CC BY-NC-ND 4.0 ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.E7055A80 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.eclinm.2023.102221 |
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