TY - JOUR
T1 - Phase II study of single-agent nivolumab in patients with myelofibrosis
AU - Abou Dalle, Iman
AU - Kantarjian, Hagop
AU - Daver, Naval
AU - Masarova, Lucia
AU - Pemmaraju, Naveen
AU - Bose, Prithivaj
AU - Garcia-Manero, Guillermo
AU - Verstovsek, Srdan
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Checkpoint inhibitor
KW - Myelofibrosis
KW - Myeloproliferative neoplasm
KW - Nivolumab
KW - PD-L1
UR - http://www.scopus.com/inward/record.url?scp=85111712373&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111712373&partnerID=8YFLogxK
U2 - 10.1007/s00277-021-04618-5
DO - 10.1007/s00277-021-04618-5
M3 - Article
C2 - 34350483
AN - SCOPUS:85111712373
SN - 0939-5555
VL - 100
SP - 2957
EP - 2960
JO - Annals of Hematology
JF - Annals of Hematology
IS - 12
ER -