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Updated: Sep 29, 2026
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Pilot study of recombinant human soluble tumor necrosis factor receptor (TNFR:Fc) in patients with low risk
Craig Rosenfeld1, Cindi Bedell
1craig.rosenfeld@usoncology.com
Abstract:
In low risk myelodysplastic syndrome (MDS), increased apoptosis of marrow cells is a reproducible finding. Cytokines may drive this apoptosis. Several studies have demonstrated elevated levels of tumor necrosis factor-alpha (TNF-alpha) in MDS. Soluble tumor necrosis factor receptor (TNFR:Fc) can eliminate biologically active TNF in vivo. This data provided the rationale for a clinical trial of TNFR:Fc in low risk MDS. Eligibility was limited to cytopenic MDS patients with < 10% marrow blasts. Secondary MDS was an exclusion. The study design was to administer 25mg TNFR:Fc twice a week for 10 weeks. Toxicity did not exceed grade 1. No responses were observed in the 10 treated patients and one had disease progression. At this dosing schedule, TNFR:Fc is unlikely to ameliorate cytopenias in low risk MDS.
Insights
This study investigated tumor necrosis factor receptor (TNFR:Fc) for low-risk myelodysplastic syndromes (MDS). The treatment did not improve cytopenias in patients with MDS, suggesting this approach is ineffective at the tested dosage.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Low-risk myelodysplastic syndromes (MDS) are characterized by increased marrow cell apoptosis, potentially driven by cytokines like tumor necrosis factor-alpha (TNF-alpha).
- Elevated TNF-alpha levels are observed in MDS patients, indicating its potential role in disease pathogenesis.
Purpose of the Study:
- To evaluate the efficacy of soluble tumor necrosis factor receptor (TNFR:Fc) in treating low-risk myelodysplastic syndromes (MDS).
- To determine if TNFR:Fc can ameliorate cytopenias in patients with low-risk MDS.
Main Methods:
- A clinical trial was conducted involving patients with low-risk MDS and cytopenias (<10% marrow blasts), excluding secondary MDS.
- Patients received 25mg of TNFR:Fc twice weekly for 10 weeks.
- Toxicity and treatment response were assessed.
Main Results:
- No significant responses were observed in the 10 treated patients.
- One patient experienced disease progression during the trial.
- Toxicity was limited to Grade 1.
Conclusions:
- The tested dosing schedule of TNFR:Fc (25mg twice weekly for 10 weeks) was ineffective in ameliorating cytopenias in low-risk MDS.
- Further investigation into alternative dosing or therapeutic strategies targeting TNF-alpha in MDS may be warranted.
