Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey

R. Zeiser; A. Burchert; C. Lengerke; M. Verbeek; K. Maas-Bauer; S. K. Metzelder; S. Spoerl; M. Ditschkowski; M. Ecsedi; K. Sockel; F. Ayuk; S. Ajib; F. S. De Fontbrune; I. K. Na; L. Penter; U. Holtick; D. Wolf; E. Schuler; E. Meyer; P. Apostolova; H. Bertz; R. Marks; M. Lübbert; R. Wäsch; C. Scheid; F. Stölzel; R. Ordemann; G. Bug; G. Kobbe; R. Negrin; M. Brune; A. Spyridonidis; A. Schmitt-Gräff; W. Van Der Velden; G. Huls; S. Mielke; G. U. Grigoleit; J. Kuball; R. Flynn; G. Ihorst; J. Du; B. R. Blazar; R. Arnold; N. Kröger; J. Passweg; J. Halter; G. Socié; D. Beelen; C. Peschel; A. Neubauer; J. Finke; J. Duyster; N. Von Bubnoff

doi:10.1038/leu.2015.212

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey

R. Zeiser, A. Burchert, C. Lengerke, M. Verbeek, K. Maas-Bauer, S. K. Metzelder, S. Spoerl, M. Ditschkowski, M. Ecsedi, K. Sockel, F. Ayuk, S. Ajib, F. S. De Fontbrune, I. K. Na, L. Penter, U. Holtick, D. Wolf, E. Schuler, E. Meyer, P. ApostolovaH. Bertz, R. Marks, M. Lübbert, R. Wäsch, C. Scheid, F. Stölzel, R. Ordemann, G. Bug, G. Kobbe, R. Negrin, M. Brune, A. Spyridonidis, A. Schmitt-Gräff, W. Van Der Velden, G. Huls, S. Mielke, G. U. Grigoleit, J. Kuball, R. Flynn, G. Ihorst, J. Du, B. R. Blazar, R. Arnold, N. Kröger, J. Passweg, J. Halter, G. Socié, D. Beelen, C. Peschel, A. Neubauer, J. Finke, J. Duyster, N. Von Bubnoff

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Abstract

Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

Original language	English (US)
Pages (from-to)	2062-2068
Number of pages	7
Journal	Leukemia
Volume	29
Issue number	10
DOIs	https://doi.org/10.1038/leu.2015.212
State	Published - Oct 1 2015

Bibliographical note

Funding Information:
FA, UH, CS, GB, JK, NK, NVB: Research support from Novartis, Bristol Meyer Squibb. DW: grants and personal fees from Novartis. RZ: Speakers fee from Bristol Meyer Squibb, travel grant from Gilead. All grants from Novartis were outside/unrelated to the submitted work. The other authors declare no conflict of interest.

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

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Zeiser, R., Burchert, A., Lengerke, C., Verbeek, M., Maas-Bauer, K., Metzelder, S. K., Spoerl, S., Ditschkowski, M., Ecsedi, M., Sockel, K., Ayuk, F., Ajib, S., De Fontbrune, F. S., Na, I. K., Penter, L., Holtick, U., Wolf, D., Schuler, E., Meyer, E., ... Von Bubnoff, N. (2015). Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey. Leukemia, 29(10), 2062-2068. https://doi.org/10.1038/leu.2015.212

Zeiser, R, Burchert, A, Lengerke, C, Verbeek, M, Maas-Bauer, K, Metzelder, SK, Spoerl, S, Ditschkowski, M, Ecsedi, M, Sockel, K, Ayuk, F, Ajib, S, De Fontbrune, FS, Na, IK, Penter, L, Holtick, U, Wolf, D, Schuler, E, Meyer, E, Apostolova, P, Bertz, H, Marks, R, Lübbert, M, Wäsch, R, Scheid, C, Stölzel, F, Ordemann, R, Bug, G, Kobbe, G, Negrin, R, Brune, M, Spyridonidis, A, Schmitt-Gräff, A, Van Der Velden, W, Huls, G, Mielke, S, Grigoleit, GU, Kuball, J, Flynn, R, Ihorst, G, Du, J, Blazar, BR, Arnold, R, Kröger, N, Passweg, J, Halter, J, Socié, G, Beelen, D, Peschel, C, Neubauer, A, Finke, J, Duyster, J & Von Bubnoff, N 2015, 'Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey', Leukemia, vol. 29, no. 10, pp. 2062-2068. https://doi.org/10.1038/leu.2015.212

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title = "Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey",

abstract = "Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.",

author = "R. Zeiser and A. Burchert and C. Lengerke and M. Verbeek and K. Maas-Bauer and Metzelder, {S. K.} and S. Spoerl and M. Ditschkowski and M. Ecsedi and K. Sockel and F. Ayuk and S. Ajib and {De Fontbrune}, {F. S.} and Na, {I. K.} and L. Penter and U. Holtick and D. Wolf and E. Schuler and E. Meyer and P. Apostolova and H. Bertz and R. Marks and M. L{\"u}bbert and R. W{\"a}sch and C. Scheid and F. St{\"o}lzel and R. Ordemann and G. Bug and G. Kobbe and R. Negrin and M. Brune and A. Spyridonidis and A. Schmitt-Gr{\"a}ff and {Van Der Velden}, W. and G. Huls and S. Mielke and Grigoleit, {G. U.} and J. Kuball and R. Flynn and G. Ihorst and J. Du and Blazar, {B. R.} and R. Arnold and N. Kr{\"o}ger and J. Passweg and J. Halter and G. Soci{\'e} and D. Beelen and C. Peschel and A. Neubauer and J. Finke and J. Duyster and {Von Bubnoff}, N.",

note = "Funding Information: FA, UH, CS, GB, JK, NK, NVB: Research support from Novartis, Bristol Meyer Squibb. DW: grants and personal fees from Novartis. RZ: Speakers fee from Bristol Meyer Squibb, travel grant from Gilead. All grants from Novartis were outside/unrelated to the submitted work. The other authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

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doi = "10.1038/leu.2015.212",

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T1 - Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation

T2 - A multicenter survey

AU - Zeiser, R.

AU - Burchert, A.

AU - Lengerke, C.

AU - Verbeek, M.

AU - Maas-Bauer, K.

AU - Metzelder, S. K.

AU - Spoerl, S.

AU - Ditschkowski, M.

AU - Ecsedi, M.

AU - Sockel, K.

AU - Ayuk, F.

AU - Ajib, S.

AU - De Fontbrune, F. S.

AU - Na, I. K.

AU - Penter, L.

AU - Holtick, U.

AU - Wolf, D.

AU - Schuler, E.

AU - Meyer, E.

AU - Apostolova, P.

AU - Bertz, H.

AU - Marks, R.

AU - Lübbert, M.

AU - Wäsch, R.

AU - Scheid, C.

AU - Stölzel, F.

AU - Ordemann, R.

AU - Bug, G.

AU - Kobbe, G.

AU - Negrin, R.

AU - Brune, M.

AU - Spyridonidis, A.

AU - Schmitt-Gräff, A.

AU - Van Der Velden, W.

AU - Huls, G.

AU - Mielke, S.

AU - Grigoleit, G. U.

AU - Kuball, J.

AU - Flynn, R.

AU - Ihorst, G.

AU - Du, J.

AU - Blazar, B. R.

AU - Arnold, R.

AU - Kröger, N.

AU - Passweg, J.

AU - Halter, J.

AU - Socié, G.

AU - Beelen, D.

AU - Peschel, C.

AU - Neubauer, A.

AU - Finke, J.

AU - Duyster, J.

AU - Von Bubnoff, N.

N1 - Funding Information: FA, UH, CS, GB, JK, NK, NVB: Research support from Novartis, Bristol Meyer Squibb. DW: grants and personal fees from Novartis. RZ: Speakers fee from Bristol Meyer Squibb, travel grant from Gilead. All grants from Novartis were outside/unrelated to the submitted work. The other authors declare no conflict of interest. Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2015/10/1

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N2 - Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

AB - Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

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Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey

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