Changes in bone marrow fibrosis during momelotinib or
ruxolitinib therapy do not correlate with efficacy outcomes in
patients with myelofibrosis

J 2024

Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis

OH, Stephen T, Srdan VERSTOVSEK, Vikas GUPTA, Uwe PLATZBECKER, Timothy DEVOS et. al.

Basic information

Original name

Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis

Authors

OH, Stephen T, Srdan VERSTOVSEK, Vikas GUPTA, Uwe PLATZBECKER, Timothy DEVOS, Jean-Jacques KILADJIAN, Donal P MCLORNAN, Andrew PERKINS, Maria Laura FOX, Mary Frances MCMULLIN, Adam J MEAD, Miklos EGYED, Jiří MAYER (203 Czech Republic, belonging to the institution), Tomasz SACHA, Jun KAWASHIMA, Mei HUANG, Bryan STROUSE and Ruben MESA

Edition

eJHaem, Hoboken, Wiley, 2024, 2688-6146

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/jha2.854

UT WoS

001216592400041

Keywords in English

bone marrow fibrosis; JAK inhibitor; momelotinib; myelofibrosis; ruxolitinib

Abstract

V originále

Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor-naive patients from SIMPLIFY-1 (NCT01969838), a double-blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of >= 1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with >= 1-grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.

Citovat

OH, Stephen T, Srdan VERSTOVSEK, Vikas GUPTA, Uwe PLATZBECKER, Timothy DEVOS, Jean-Jacques KILADJIAN, Donal P MCLORNAN, Andrew PERKINS, Maria Laura FOX, Mary Frances MCMULLIN, Adam J MEAD, Miklos EGYED, Jiří MAYER, Tomasz SACHA, Jun KAWASHIMA, Mei HUANG, Bryan STROUSE and Ruben MESA. Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis. eJHaem. Hoboken: Wiley, 2024, vol. 5, No 1, p. 105-116. ISSN 2688-6146. Available from: https://dx.doi.org/10.1002/jha2.854.

@article{2423778,
   author = {Oh, Stephen T and Verstovsek, Srdan and Gupta, Vikas and Platzbecker, Uwe and Devos, Timothy and Kiladjian, JeanandJacques and McLornan, Donal P and Perkins, Andrew and Fox, Maria Laura and McMullin, Mary Frances and Mead, Adam J and Egyed, Miklos and Mayer, Jiří and Sacha, Tomasz and Kawashima, Jun and Huang, Mei and Strouse, Bryan and Mesa, Ruben},
   article_location = {Hoboken},
   article_number = {1},
   doi = {http://dx.doi.org/10.1002/jha2.854},
   keywords = {bone marrow fibrosis; JAK inhibitor; momelotinib; myelofibrosis; ruxolitinib},
   language = {eng},
   issn = {2688-6146},
   journal = {eJHaem},
   title = {Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis},
   url = {https://onlinelibrary.wiley.com/doi/10.1002/jha2.854},
   volume = {5},
   year = {2024}
}

TY  - JOUR
ID  - 2423778
AU  - Oh, Stephen T - Verstovsek, Srdan - Gupta, Vikas - Platzbecker, Uwe - Devos, Timothy - Kiladjian, Jean-Jacques - McLornan, Donal P - Perkins, Andrew - Fox, Maria Laura - McMullin, Mary Frances - Mead, Adam J - Egyed, Miklos - Mayer, Jiří - Sacha, Tomasz - Kawashima, Jun - Huang, Mei - Strouse, Bryan - Mesa, Ruben
PY  - 2024
TI  - Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis
JF  - eJHaem
VL  - 5
IS  - 1
SP  - 105-116
EP  - 105-116
PB  - Wiley
SN  - 26886146
KW  - bone marrow fibrosis
KW  - JAK inhibitor
KW  - momelotinib
KW  - myelofibrosis
KW  - ruxolitinib
UR  - https://onlinelibrary.wiley.com/doi/10.1002/jha2.854
N2  - Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor-naive patients from SIMPLIFY-1 (NCT01969838), a double-blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of >= 1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with >= 1-grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.
ER  -

OH, Stephen T, Srdan VERSTOVSEK, Vikas GUPTA, Uwe PLATZBECKER, Timothy DEVOS, Jean-Jacques KILADJIAN, Donal P MCLORNAN, Andrew PERKINS, Maria Laura FOX, Mary Frances MCMULLIN, Adam J MEAD, Miklos EGYED, Jiří MAYER, Tomasz SACHA, Jun KAWASHIMA, Mei HUANG, Bryan STROUSE and Ruben MESA. Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis. \textit{eJHaem}. Hoboken: Wiley, 2024, vol.~5, No~1, p.~105-116. ISSN~2688-6146. Available from: https://dx.doi.org/10.1002/jha2.854.

Detailed Information on Publication Record