Trial reportBlood advances2021
A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial.
Trial report in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Zanubrutinib plus Cytarabine in Patients with Refractory/Relapsed Primary Central Nervous System Lymphoma.Acta haematologica · 2024Trial
- Article
- Primary central nervous system lymphoma in the molecular era: genomic drivers, liquid biopsy, and targeted therapeutic strategies.Annals of hematology · 2026Review
- A Case of Relapsed/Refractory Primary Central Nervous System B-Cell Lymphoma with Renal Insufficiency Successfully Treated with LinperlisibTurkish journal of haematology : official journal of Turkish Society of Haematology · 2026Article
- ICE polychemotherapy is an efficient salvage treatment in primary central nervous system lymphoma: an LOC network study.Blood advances · 2025Article
- Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma.Frontiers in neurology · 2025Article
- Advances in primary large B-cell lymphoma of immune-privileged sites.Frontiers in immunology · 2025Review
- Novel Therapies for Primary Central Nervous System Lymphomas.Current neurology and neuroscience reports · 2024Review
- Recent advances and challenges in primary central nervous system lymphoma: a narrative review.Translational cancer research · 2023Review
- Survival, prognostic factors, hospitalization time and clinical performance status after first cerebral relapse or progression in 54 patients with primary CNS lymphoma not eligible for high dose chemotherapy: a retrospective analysis.Neurological research and practice · 2023Article
- High-dose methotrexate, thiotepa, orelabrutinib combined with or without rituximab in primary or secondary central nervous system diffuse large B-cell lymphoma: a single-center retrospective analysis.Journal of Cancer · 2023Article
- A review of FDA approved drugs and their formulations for the treatment of breast cancer.Frontiers in pharmacology · 2023Review
- Treatment Options for Recurrent Primary CNS Lymphoma.Current treatment options in oncology · 2022Review
- Nephrotoxicity in cancer treatment: An update.Advances in cancer research · 2022Article
- Systemic Relapse in a Young Adult Patient with Primary CNS Diffuse Large B-Cell Lymphoma.Case reports in hematology · 2022Article
Corrections and comments
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Authors and funding
22 authors at 16 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.