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Phase II study of single-agent nivolumab in patients with myelofibrosis

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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

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Authors and Affiliations

  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0428, Houston, TX, 77030, USA

    Iman Abou Dalle, Hagop Kantarjian, Naval Daver, Lucia Masarova, Naveen Pemmaraju, Prithivaj Bose, Guillermo Garcia-Manero & Srdan Verstovsek

Authors
  1. Iman Abou Dalle
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  2. Hagop Kantarjian
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  3. Naval Daver
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  4. Lucia Masarova
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  5. Naveen Pemmaraju
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  6. Prithivaj Bose
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  7. Guillermo Garcia-Manero
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  8. Srdan Verstovsek
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Contributions

IA and SV wrote the manuscript; SV designed and coordinated the study, treated patients, directed the clinical trial; HK, LM, ND, PB, NP, and GGM enrolled the patients and conducted the research; IA analyzed the data. All of the authors participated in the discussion, and have reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Srdan Verstovsek.

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The authors declare no competing interests.

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Key points

• Nivolumab demonstrates no clinical activity in patients with advanced myelofibrosis, after failure of ruxolitinib therapy.

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Abou Dalle, I., Kantarjian, H., Daver, N. et al. Phase II study of single-agent nivolumab in patients with myelofibrosis. Ann Hematol 100, 2957–2960 (2021). https://doi.org/10.1007/s00277-021-04618-5

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  • DOI: https://doi.org/10.1007/s00277-021-04618-5

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