A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial
| Autor: | Kim Linton, Sridhar Chaganti, Kate Cwynarski, Josh Wright, Dominic Culligan, Roderick J. Johnson, Stefanie Thust, Ayesha S. Ali, Louise Hopkins, Aimee Jackson, Jeffery Smith, Andrew Davies, Andrés J.M. Ferreri, Shireen Kassam, Christopher P. Fox, Catherine Thomas, Ian Chau, David J. Lewis, Graham P. Collins, Nicolas Martinez-Calle, Dorothee P. Auer, Graham McIlroy |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty medicine.medical_treatment ThioTEPA Neutropenia Transplantation Autologous Lymphoma Non-Hodgkin/drug therapy Autologous stem-cell transplantation Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Prospective Studies Chemotherapy Ifosfamide Manchester Cancer Research Centre business.industry Lymphoma Non-Hodgkin Antineoplastic Combined Chemotherapy Protocols/adverse effects ResearchInstitutes_Networks_Beacons/mcrc Hematopoietic Stem Cell Transplantation Primary central nervous system lymphoma Hematology Thiotepa/therapeutic use medicine.disease Combined Modality Therapy Regimen Rituximab business Thiotepa medicine.drug |
| Zdroj: | Fox, C P, Ali, A S, McIlroy, G, Thust, S, Martinez-Calle, N, Jackson, A E, Hopkins, L M, Thomas, C M, Kassam, S, Wright, J, Chaganti, S, Smith, J, Chau, I, Culligan, D, Linton, K M, Collins, G P, Ferreri, A J M, Lewis, D, Davies, A J, Johnson, R, Auer, D P & Cwynarski, K 2021, ' A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma : the TIER trial ', Blood Advances, vol. 5, no. 20, pp. 4073-4082 . https://doi.org/10.1182/bloodadvances.2021004779 |
| ISSN: | 2473-9537 2473-9529 2014-0002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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