dc.contributor.author | Fox, CP | |
dc.contributor.author | Ali, AS | |
dc.contributor.author | McIlroy, G | |
dc.contributor.author | Thust, S | |
dc.contributor.author | Martinez-Calle, N | |
dc.contributor.author | Jackson, AE | |
dc.contributor.author | Hopkins, LM | |
dc.contributor.author | Thomas, CM | |
dc.contributor.author | Kassam, S | |
dc.contributor.author | Wright, J | |
dc.contributor.author | Chaganti, S | |
dc.contributor.author | Smith, J | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Culligan, D | |
dc.contributor.author | Linton, KM | |
dc.contributor.author | Collins, GP | |
dc.contributor.author | Ferreri, AJM | |
dc.contributor.author | Lewis, D | |
dc.contributor.author | Davies, AJ | |
dc.contributor.author | Johnson, R | |
dc.contributor.author | Auer, DP | |
dc.contributor.author | Cwynarski, K | |
dc.date.accessioned | 2022-01-07T13:24:10Z | |
dc.date.available | 2022-01-07T13:24:10Z | |
dc.identifier.citation | Blood advances, 2021, 5 (20), pp. 4073 - 4082 | |
dc.identifier.issn | 2473-9529 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4948 | |
dc.identifier.eissn | 2473-9537 | |
dc.identifier.doi | 10.1182/bloodadvances.2021004779 | |
dc.description.abstract | 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. | |
dc.format | Print | |
dc.format.extent | 4073 - 4082 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-05-07 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1182/bloodadvances.2021004779 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Blood advances | |
pubs.issue | 20 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 5 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Chau, Ian | |