TY - JOUR
T1 - Refractory acute graft-versus-host disease
T2 - A new working definition beyond corticosteroid refractoriness
AU - Mohty, Mohamad
AU - Holler, Ernst
AU - Jagasia, Madan
AU - Jenq, Robert
AU - Malard, Florent
AU - Martin, Paul
AU - Socié, Gérard
AU - Zeiser, Robert
N1 - Funding Information:
Conflict-of-interest disclosure: M.M. reports grants and/or lecture honoraria from Astellas, GlaxoSmithKline, Janssen, Sanofi, Maat Pharma, JAZZ Pharmaceuticals, Celgene, Amgen, BMS, Takeda, Pfizer, Novartis, and Roche. M.J. reports honoraria for consulting/advisor role from Novartis, Incyte, Kadmon Mallinckrodt, and Ocugen. R.J. reports honoraria from Seres Therapeutics, Kaleido Biosciences, Merck, Micro-biomeDx, KariusDx, and Maat Pharma. F.M. reports lecture honoraria from Therakos/Mallinckrodt, Biocodex, Janssen, Keocyt, Sanofi, JAZZ Pharmaceuticals, and Astellas. P.M. reports participation in advisory boards or consultation for Neovii Biotech, Genentech, Enlivex, Phar-macyclics, Rigel, Talaris, and Mesoblast; institutional research funding from Abgenomics; and financial support without an honorarium for a sponsored meeting by Janssen. G.S. reports consulting for Alexion and Elsalys and honorarium from Novartis, Amgen, and Incyte. R.Z. reports speaker fees from Novartis, Incyte, and Therakos/Mallinckrodt.
Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/10/22
Y1 - 2020/10/22
N2 - Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation. Only half of patients with severe acute GVHD respond to first-line treatment with corticosteroids and, for several decades, there was no optimal second-line treatment of patients with corticosteroid-refractory acute GVHD. Ruxolitinib was recently approved for the treatment of corticosteroid-refractory acute GVHD in adult and pediatric patients 12 years and older. Thus, it is important to define the patient population that would now be considered as refractory to ruxolitinib vs ruxolitinib dependent. Here, we propose to define ruxolitinib-refractory acute GVHD as disease that shows: (1) progression of GVHD compared with baseline after at least 5 to 10 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement; (2) lack of improvement in GVHD (partial response or better) compared with baseline after ‡14 days of treatment with ruxolitinib; or (3) loss of response, defined as objective worsening of GVHD determined by increase in stage, grade, or new organ involvement at any time after initial improvement. GVHD manifestations that persist without improvement in patients who had a grade ‡3 treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib would serve as a clinical indication for additional treatment. In addition, absence of complete response or very good partial response at day 28 after ruxolitinib could be considered as an eligibility criterion.
AB - Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation. Only half of patients with severe acute GVHD respond to first-line treatment with corticosteroids and, for several decades, there was no optimal second-line treatment of patients with corticosteroid-refractory acute GVHD. Ruxolitinib was recently approved for the treatment of corticosteroid-refractory acute GVHD in adult and pediatric patients 12 years and older. Thus, it is important to define the patient population that would now be considered as refractory to ruxolitinib vs ruxolitinib dependent. Here, we propose to define ruxolitinib-refractory acute GVHD as disease that shows: (1) progression of GVHD compared with baseline after at least 5 to 10 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement; (2) lack of improvement in GVHD (partial response or better) compared with baseline after ‡14 days of treatment with ruxolitinib; or (3) loss of response, defined as objective worsening of GVHD determined by increase in stage, grade, or new organ involvement at any time after initial improvement. GVHD manifestations that persist without improvement in patients who had a grade ‡3 treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib would serve as a clinical indication for additional treatment. In addition, absence of complete response or very good partial response at day 28 after ruxolitinib could be considered as an eligibility criterion.
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U2 - 10.1182/BLOOD.2020007336
DO - 10.1182/BLOOD.2020007336
M3 - Review article
C2 - 32756949
AN - SCOPUS:85094221843
SN - 0006-4971
VL - 136
SP - 1903
EP - 1906
JO - Blood
JF - Blood
IS - 17
ER -