Academic Journal
A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial.
| العنوان: | A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial. |
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| المؤلفون: | Fox, CP, Ali, AS, McIlroy, G, Thust, S, Martinez-Calle, N, Jackson, AE, Hopkins, LM, Thomas, CM, Kassam, S, Wright, J, Chaganti, S, Smith, J, Chau, I, Culligan, D, Linton, KM, Collins, GP, Ferreri, AJM, Lewis, D, Davies, AJ, Johnson, R, Auer, DP, Cwynarski, K |
| المساهمون: | Chau, Ian |
| سنة النشر: | 2022 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| الوصف: | Relapsed or refractory primary central nervous system lymphoma (rrPCNSL) confers a poor prognosis with no accepted standard of care. Very few prospective studies have been conducted in this patient group. This study was a multicenter phase 1/2 study that investigated thiotepa in combination with ifosfamide, etoposide, and rituximab (TIER) for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. A 3 + 3 design investigated the recommended phase 2 dose of thiotepa for a single-stage phase 2 cohort by assessing the activity of 2 cycles of TIER against rrPCNSL. The primary outcome was overall response rate. The dose-finding study demonstrated that 50 mg/m2 of thiotepa could be safely delivered within the TIER regimen. No dose-limiting toxicities were encountered in phase 1, and TIER was well-tolerated by the 27 patients treated in phase 2. The most common grade 3 to 4 toxicities were neutropenia (56% of patients) and thrombocytopenia (39%). An overall response was confirmed in 14 patients (52%), which met the prespecified threshold for clinically relevant activity. The median progression-free survival was 3 months (95% confidence interval [CI], 2 to 6 months) and overall survival 5 months (95% CI, 3 to 9 months). Exploratory analyses suggest a greater benefit for thiotepa-naïve patients. Six patients successfully completed autologous stem cell transplantation (ASCT) consolidation, with 4 experiencing durable remissions after a median follow-up of 50 months. The TIER regimen can be delivered safely and is active against rrPCNSL. When it is followed by ASCT, it can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor, and novel treatment strategies are urgently needed. This trial was registered at https://www.clinicaltrialsregister.eu/ctr-search/search as EudraCT 2014-000227-24 and ISRCTN 12857473. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; 4082; application/pdf |
| اللغة: | English |
| تدمد: | 2473-9529 2473-9537 |
| Relation: | Blood advances, 2021, 5 (20), pp. 4073 - 4082; https://repository.icr.ac.uk/handle/internal/4948 |
| DOI: | 10.1182/bloodadvances.2021004779 |
| الاتاحة: | https://repository.icr.ac.uk/handle/internal/4948 https://doi.org/10.1182/bloodadvances.2021004779 |
| Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0 |
| رقم الانضمام: | edsbas.E6FCDFE3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 24739529 24739537 |
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| DOI: | 10.1182/bloodadvances.2021004779 |