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dc.contributor.authorFox, C. P.
dc.contributor.authorAli, A. S.
dc.contributor.authorMcIlroy, G.
dc.contributor.authorThust, S.
dc.contributor.authorMartinez-Calle, N.
dc.contributor.authorJackson, A. E.
dc.contributor.authorHopkins, L. M.
dc.contributor.authorThomas, C. M.
dc.contributor.authorKassam, S.
dc.contributor.authorWright, J.
dc.contributor.authorChaganti, S.
dc.contributor.authorSmith, J.
dc.contributor.authorChau, I.
dc.contributor.authorCulligan, D.
dc.contributor.authorLinton, K. M.
dc.contributor.authorCollins, G. P.
dc.contributor.authorFerreri, A. J. M.
dc.contributor.authorLewis, D.
dc.contributor.authorDavies, A. J.
dc.contributor.authorJohnson, R.
dc.contributor.authorAuer, D. P.
dc.contributor.authorCwynarski, K.
dc.date.accessioned2022-02-23T12:56:15Z
dc.date.available2022-02-23T12:56:15Z
dc.date.issued2021en
dc.identifier.citationFox CP, Ali AS, McIlroy G, Thust S, Martinez-Calle N, Jackson AE, et al. A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial [Internet]. Vol. 5, Blood Advances. American Society of Hematology; 2021. p. 4073–82.en
dc.identifier.pmid34464973en
dc.identifier.doi10.1182/bloodadvances.2021004779en
dc.identifier.urihttp://hdl.handle.net/10541/625092
dc.description.abstractRelapsed 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.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1182/bloodadvances.2021004779en
dc.titleA phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trialen
dc.typeArticleen
dc.identifier.journalBlood Advancesen
dc.description.noteen]


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