CTIM-06. NIACIN MODULATES IMMUNE RESPONSES IN A PHASE I DOSE-ESCALATION CLINICAL TRIAL OF NEWLY DIAGNOSED GLIOBLASTOMA
Bibliographic record
Abstract
Abstract INTRODUCTION Immunotherapies such as immune checkpoint blockade have transformed cancer care in solid tumors such as melanoma, but have limited success in glioblastoma (GBM). GBM resists immunotherapies by fostering a profoundly immunosuppressive local microenvironment and altering systemic immunophenotypes. This involves decreasing CD4+ and CD8+ T cell and NK cell frequencies in the peripheral blood while expanding immunosuppressive myeloid subsets such as non-classical monocytes. In preclinical studies, we showed niacin (vitamin B3) administration ameliorates immunosuppression in the peripheral blood, alters leukocyte infiltration into the tumor, and improves outcomes. In this phase I trial, the objective is to determine whether niacin modulates systemic immunity in newly diagnosed GBM patients. METHODS This first-in-human phase I clinical trial (NCT04677049) investigates the immunomodulatory effects of oral controlled-release niacin (Niacin CRTTM) administered according to a dose escalation schedule (500-3,000mg daily) alongside standard of care surgery and chemoradiation in patients with newly diagnosed GBM. RESULTS Of the 15 patients enrolled, median age was 57 years and 60% were male. A gross total resection was achieved in 67% of patients, while 7% underwent biopsy only. Escalating niacin doses correlated with increasing frequencies of circulating memory T cells (p = 0.020) and natural killer cells (p = 0.027), while non-classical monocyte frequencies decreased (p = 0.019). Furthermore, niacin elevated serum levels of the pro-inflammatory cytokine interleukin (IL)-12p70 (p = 0.0078) and granulocyte colony-stimulating factor (G-CSF; p = 0.023), while reducing growth-regulated alpha protein (GROa; p = 0.039). DISCUSSION These data demonstrate that niacin exerts systemic immunomodulatory effects in GBM patients, shifting the immune landscape towards an anti-tumor profile and supporting further evaluation of niacin as a potential therapeutic adjunct. The promise of niacin as an adjunct is enhanced by its low-cost, accessibility, and established safety profile.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".