Related Experiment Video
Updated: Oct 25, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Phase II study of single-agent nivolumab in patients with myelofibrosis
Iman Abou Dalle1, Hagop Kantarjian1, Naval Daver1
1Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0428, Houston, TX, 77030, USA.
Abstract:
Dysregulated JAK-STAT signaling in myelofibrosis induces pro-inflammatory cytokines, which suppresses T cell proliferation and differentiation, likely responsible for disease progression. The PD-1 pathway, found to be overexpressed in myeloid malignancies, has gained great interest as a therapeutic target, where a significant unmet need exists for novel therapeutic strategies. Preclinical models showed JAK2 mutant cells had higher expression of PD-L1; furthermore, JAK2 mutant xenografts treated with PD-1 inhibition had prolonged survival and reduction in JAK2 allele burden. We evaluated the efficacy and safety of single-agent nivolumab in 8 adult patients with myelofibrosis. Nivolumab was given at 3 mg/kg every 2 weeks for 8 doses, then every 12 weeks for up to 4 years, or until disease progression or toxicity. The median number of nivolumab doses received was 6 [range, 5-16 doses]. Five patients had stable disease including spleen size, total symptom score, and blood requirements for a median of 3.3 months [range, 2.3-15.2 months]. After a median follow-up of 57 months, two patients were still alive. The median overall survival was 6.1 months [range, 3.2-57.4 months]. Due to failure to meet the predetermined efficacy endpoint, the study was terminated early. Trial registration: Clinical trials.gov NCT: 02,421,354.
Insights
This study investigated nivolumab for myelofibrosis, finding it did not meet efficacy endpoints. Further research is needed for effective JAK-STAT and PD-1 pathway targeted therapies in myelofibrosis.
Area of Science:
- Immunology
- Oncology
- Hematology
Background:
- Dysregulated JAK-STAT signaling in myelofibrosis promotes inflammation, impairing T cell function and driving disease progression.
- The programmed cell death protein 1 (PD-1) pathway is overexpressed in myeloid malignancies, representing a potential therapeutic target.
- Preclinical data suggest PD-1 inhibition may be effective in JAK2-mutant myelofibrosis.
Purpose of the Study:
- To evaluate the efficacy and safety of single-agent nivolumab in adult patients with myelofibrosis.
- To assess nivolumab's impact on disease progression, symptoms, and survival in myelofibrosis.
Main Methods:
- A single-arm study involving 8 adult patients with myelofibrosis.
- Nivolumab administered at 3 mg/kg every 2 weeks for 8 doses, then every 12 weeks, up to 4 years or until progression/toxicity.
- Data collected on disease status, symptoms, and survival.
Main Results:
- Five patients achieved stable disease for a median of 3.3 months.
- Median overall survival was 6.1 months.
- The study was terminated early due to failure to meet predefined efficacy endpoints.
Conclusions:
- Single-agent nivolumab did not demonstrate sufficient efficacy in this cohort of myelofibrosis patients.
- The PD-1 pathway may not be a viable standalone therapeutic target in myelofibrosis.
- Novel therapeutic strategies targeting both JAK-STAT and PD-1 pathways warrant further investigation.
Related Concept Videos
02:56Treatment Resistant Cancers
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents