70
Views
0
CrossRef citations to date
0
Altmetric
Review

New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature

, &
Pages 791-799 | Received 21 Apr 2024, Accepted 03 Jul 2024, Published online: 09 Jul 2024

References

  • Bolanos-Meade J, Hamadani M, Wu J, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. N Engl J Med. 2023;388(25):2338–2348. doi: 10.1056/NEJMoa2215943
  • Watkins B, Qayed M, McCracken C, et al. Phase II trial of costimulation blockade with abatacept for prevention of acute GVHD. J Clin Oncol. 2021;39(17):1865–1877. doi: 10.1200/JCO.20.01086
  • Zeiser R, Blazar BR, Longo DL. Acute graft-versus-host disease — biologic process, prevention, and therapy. N Engl J Med. 2017;377(22):2167–2179. doi: 10.1056/NEJMra1609337
  • Filipovich AH, Weisdorf D, Pavletic S, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Of Blood And Marrow Transplant. 2005;11(12):945–956. doi: 10.1016/j.bbmt.2005.09.004
  • Martin PJ, Rizzo JD, Wingard JR, et al. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012;18(8):1150–1163. doi: 10.1016/j.bbmt.2012.04.005
  • Schoemans HM, Lee SJ, Ferrara JL, et al. EBMT−NIH−CIBMTR task force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401–1415. doi: 10.1038/s41409-018-0204-7
  • Westin JR, Saliba RM, De Lima M, et al. Steroid-refractory acute GVHD: predictors and outcomes. Adv Hematol. 2011;2011:1–8. doi: 10.1155/2011/601953
  • Przepiorka D, Luo L, Subramaniam S, et al. FDA approval summary: ruxolitinib for treatment of steroid-refractory acute graft-versus-host disease. Oncologist. 2020;25(2):e328–e34. doi: 10.1634/theoncologist.2019-0627
  • Benito AI, Furlong T, Martin PJ, et al. Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation. 2001;72(12):1924–1929. doi: 10.1097/00007890-200112270-00010
  • Hsu B, May R, Carrum G, et al. Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey. Bone Marrow Transplant. 2001;28(10):945–950. doi: 10.1038/sj.bmt.1703269
  • Furlong T, Martin P, Flowers MED, et al. Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant. 2009;44(11):739–748. doi: 10.1038/bmt.2009.76
  • Socie G, Vigouroux S, Yakoub-Agha I, et al. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD. Blood. 2017;129(5):643–649. doi: 10.1182/blood-2016-09-738625
  • Solh MM, Farnham C, Solomon SR, et al. Extracorporeal photopheresis (ECP) improves overall survival in the treatment of steroid refractory acute graft-versus-host disease (SR aGvHD). Bone Marrow Transplant. 2023;58(2):168–174. doi: 10.1038/s41409-022-01860-x Epub 20221109
  • Kitko CL, Abdel-Azim H, Carpenter PA, et al. A prospective, multicenter study of closed-system extracorporeal photopheresis for children with steroid-refractory acute graft-versus-Host disease. Transpl Cell Ther. 2022;28(5):.e261.1–.e261.7. doi: 10.1016/j.jtct.2022.01.025
  • Drexler B, Buser A, Infanti L, et al. Extracorporeal photopheresis in graft-versus-host disease. Transfus Med Hemother. 2020;47(3):214–225. doi: 10.1159/000508169
  • Zhang H, Chen R, Cheng J, et al. Systematic review and meta-analysis of prospective studies for ECP treatment in patients with steroid-refractory acute GVHD. Patient Prefer Adherence. 2019;9:105–111.
  • Spoerl S, Mathew NR, Bscheider M, et al. Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood. 2014;123(24):3832–3842. doi: 10.1182/blood-2013-12-543736
  • Choi J, Cooper ML, Alahmari B, et al. Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect. PLOS ONE. 2014;9(10):e109799. doi: 10.1371/journal.pone.0109799
  • Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29(10):2062–2068. doi: 10.1038/leu.2015.212
  • Jagasia M, Perales MA, Schroeder MA, et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020;135(20):1739–1749. doi: 10.1182/blood.2020004823
  • Zeiser R, Von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800–1810. doi: 10.1056/NEJMoa1917635
  • Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228–238. doi: 10.1056/NEJMoa2033122
  • Murray A, Linn SM, Yu B, et al. Real-world experience with ruxolitinib therapy for steroid-refractory acute graft versus host disease. Bone Marrow Transplant. 2024;59(6):759–764. doi: 10.1038/s41409-024-02249-8
  • Abedin S, McKenna E, Chhabra S, et al. Efficacy, toxicity, and infectious complications in Ruxolitinib-treated patients with corticosteroid-refractory graft-versus-host disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25(8):1689–1694. doi: 10.1016/j.bbmt.2019.04.003
  • Biavasco F, Ihorst G, Wasch R, et al. Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract. Bone Marrow Transplant. 2022;57(10):1500–1506. doi: 10.1038/s41409-022-01741-3
  • Mohty M, Holler E, Jagasia M, et al. Refractory acute graft-versus-host disease: a new working definition beyond corticosteroid refractoriness. Blood. 2020;136(17):1903–1906. doi: 10.1182/blood.2020007336
  • Abedin S, Rashid N, Schroeder M, et al. Ruxolitinib resistance or intolerance in steroid-refractory acute graft-versus-host disease - a real-world outcomes analysis. Br J Haematol. 2021;195(3):429–432. doi: 10.1111/bjh.17700
  • Li A-W, Dong C, Tay S-T, et al. Vedolizumab for acute gastrointestinal graft-versus-host disease: a systematic review and meta-analysis. Front Immunol. 2022;13. doi: 10.3389/fimmu.2022.1025350
  • Mehta RS, Saliba RM, Jan A, et al. Vedolizumab for steroid refractory lower gastrointestinal tract graft-versus-host disease. Transpl Cell Ther. 2021;27(3):272 e1–e5. doi: 10.1016/j.jtct.2020.12.011
  • Coltoff A, Lancman G, Kim S, et al. Vedolizumab for treatment of steroid-refractory lower gastrointestinal acute graft-versus-host disease. Bone Marrow Transplant. 2018;53(7):900–904. doi:10.1038/s41409-018-0094-8
  • Floisand Y, Schroeder MA, Chevallier P, et al. A phase 2a randomized clinical trial of intravenous vedolizumab for the treatment of steroid-refractory intestinal acute graft-versus-host disease. Bone Marrow Transplant. 2021;56(10):2477–2488. doi: 10.1038/s41409-021-01356-0
  • Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8(9):726–736. doi: 10.1038/nri2395 PubMed PMID: 19172693.
  • Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther. 2016;7(1):125. doi: 10.1186/s13287-016-0363-7
  • Zeiser R, Ringden O, Sadeghi B, et al. Novel therapies for graft versus host disease with a focus on cell therapies. Front Immunol. 2023;14:1241068. doi: 10.3389/fimmu.2023.1241068
  • Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. The Lancet. 2004;363(9419):1439–1441. doi: 10.1016/S0140-6736(04)16104-7
  • Ball LM, Bernardo ME, Roelofs H, et al. Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III-IV acute graft-versus-host disease. Br J Haematol. 2013;163(4):501–509. doi: 10.1111/bjh.12545
  • Resnick IB, Barkats C, Shapira MY, et al. Treatment of severe steroid resistant acute GVHD with mesenchymal stromal cells (MSC). Am J Blood Res. 2013;3(3):225–238.
  • Kebriaei P, Hayes J, Daly A, et al. A phase 3 randomized study of remestemcel-L versus placebo added to second-line therapy in patients with steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2020;26(5):835–844. doi: 10.1016/j.bbmt.2019.08.029
  • Zhao K, Lin R, Fan Z, et al. Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial. J Hematol Oncol. 2022;15(1):22. doi: 10.1186/s13045-022-01240-4
  • Galipeau J. The mesenchymal stromal cells dilemma–does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy. 2013;15(1):2–8. doi: 10.1016/j.jcyt.2012.10.002
  • Kakihana K, Fujioka Y, Suda W, et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood. 2016;128(16):2083–2088. doi: 10.1182/blood-2016-05-717652
  • Malard F, Loschi M, Huynh A, et al. Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial. EClinicalMedicine. 2023;62:102111. doi: 10.1016/j.eclinm.2023.102111
  • Mori Y, Yoshimoto G, Nishida R, et al. Gastrointestinal graft-versus-host disease is a risk factor for postengraftment bloodstream infection in allogeneic hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2018;24(11):2302–2309. doi: 10.1016/j.bbmt.2018.06.002 Epub 20180615
  • van Oosterhout YV, An Emst L, Schattenberg AV, et al. A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease. Blood. 2000;95(12):3693–3701. doi: 10.1182/blood.V95.12.3693.012k22_3693_3701
  • Groth C, van Groningen LFJ, Matos TR, et al. Phase I/II trial of a combination of anti-CD3/CD7 immunotoxins for steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2019;25(4):712–719. doi: 10.1016/j.bbmt.2018.10.020 PubMed PMID: 30399420; PubMed Central PMCID: PMC6595479 Epub 20181103.
  • Meyers G, Hamadani M, Martens M, et al. Lessons learned from early closure of a clinical trial for steroid-refractory acute GVHD. Bone Marrow Transplant. 2022;57(2):302–303. doi: 10.1038/s41409-021-01529-x Epub 20211123 PubMed PMID: 34815518; PubMed Central PMCID: PMC8825705.
  • Floisand Y, Lundin KEA, Lazarevic V, Kristiansen JD, Osnes LTN, Tjonnfjord GE, et al. Targeting integrin alpha4beta7 in steroid-refractory intestinal graft-versus-host disease. Biol Blood Marrow Transplant. 2017;23(1):172. doi: 10.1016/j.bbmt.2016.10.009
  • von Bonin M, Stolzel F, Goedecke A, et al. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009;43(3):245–251. doi: 10.1038/bmt.2008.316
  • Kadri N, Amu S, Iacobaeus E, et al. Current perspectives on mesenchymal stromal cell therapy for graft versus host disease. Cell Mol Immunol. 2023;20(6):613–625. doi:10.1038/s41423-023-01022-z
  • Meyers G, Hamadani M, Martens M, et al. Anti-CD3/CD7 immunoconjugate (T-Guard) for severe, steroid-refractory GVHD: final report of BMT CTN 2002. Bone Marrow Transplant. 2023;58(12):1416–1418. doi: 10.1038/s41409-023-02110-4 Epub 20230925 PubMed PMID: 37749187.
  • Abedin S, Hamadani M, Holtan SG, et al. Neihulizumab (ALTB-168) in patients with steroid-refractory acute graft-versus-host-disease (SR-aGVHD) or treatment-refractory acute graft-versus-host-disease (TR-aGVHD). Blood. 2022;140(Supplement 1):10495–10497. doi: 10.1182/blood-2022-163027
  • Hu X, Wang X, Xue X. Therapeutic perspectives of CD26 inhibitors in imune-mediated diseases. Molecules. 2022;27(14):4498. doi: 10.3390/molecules27144498
  • Bacigalupo A, Deeg HJ, Caballero D, et al. Treatment of patients with steroid refractory acute graft Vs host disease (SR-GvHD): a matched paired analysis of anti-CD26 (begelomab) compared to other treatment. Blood. 2016;128(22):671–. doi: 10.1182/blood.V128.22.671.671
  • Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther. 2006;8(Suppl 2):S3. doi: 10.1186/ar1917
  • Chen X, Das R, Komorowski R, et al. Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease. Blood. 2009;114(4):891–900. doi: 10.1182/blood-2009-01-197178
  • Ganetsky A, Frey NV, Hexner EO, et al. Tocilizumab for the treatment of severe steroid-refractory acute graft-versus-host disease of the lower gastrointestinal tract. Bone Marrow Transplant. 2019;54(2):212–217. doi: 10.1038/s41409-018-0236-z
  • Drobyski WR, Pasquini M, Kovatovic K, et al. Tocilizumab for the treatment of steroid refractory graft-versus-host disease. Biol Of Blood And Marrow Transplant. 2011;17(12):1862–1868. doi: 10.1016/j.bbmt.2011.07.001
  • Al Malki MM, London K, Baez J, et al. Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease. Blood Adv. 2023;7(17):5189–5198. doi: 10.1182/bloodadvances.2023009853
  • Schmidt-Hieber M, Fietz T, Knauf W, et al. Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease. Br J Haematol. 2005;130(4):568–574. doi: 10.1111/j.1365-2141.2005.05631.x
  • Wang JZ, Liu KY, Xu LP, et al. Basiliximab for the treatment of steroid-refractory acute graft-versus-host disease after unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation. Transplant Proc. 2011;43(5):1928–1933. doi: 10.1016/j.transproceed.2011.03.044
  • Chakupurakal G, Garcia-Marquez MA, Shimabukuro-Vornhagen A, et al. Immunological effects in patients with steroid-refractory graft-versus-host disease following treatment with basiliximab, a CD25 monoclonal antibody. Eur J Haematol. 2016;97(2):121–127. doi: 10.1111/ejh.12691
  • Chen Y-B, Perales M-A, Li S, et al. Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease. Blood. 2017;129(24):3256–3261. doi: 10.1182/blood-2017-03-772210
  • Magenau JM, Goldstein SC, Peltier D, et al. alpha(1)-antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease. Blood. 2018;131(12):1372–1379. doi: 10.1182/blood-2017-11-815746
  • Dudakov JA, Hanash AM, van den Brink MR. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. 2015;33(1):747–785. doi: 10.1146/annurev-immunol-032414-112123
  • Ponce DM, Alousi AM, Nakamura R, et al. A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract. Blood. 2023;141(12):1389–1401. doi: 10.1182/blood.2021015111
  • Poi MJ, Hofmeister CC, Johnston JS, et al. Standard pentostatin dose reductions in renal insufficiency are not adequate: selected patients with steroid-refractory acute graft-versus-host disease. Clin Pharmacokinet. 2013;52(8):705–712. doi: 10.1007/s40262-013-0064-7
  • Norona J, Apostolova P, Schmidt D, et al. Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. Blood. 2020;136(12):1442–1455. doi: 10.1182/blood.2020005957
  • Holtan SG, Hoeschen A, Cao Q, et al. Phase II, open-label clinical trial of urinary-derived human chorionic gonadotropin/epidermal growth factor for life-threatening acute graft-versus-host disease. Transplant Cell Ther. 2023;29(8):509 e1–e8. doi: 10.1016/j.jtct.2023.05.021
  • Penack O, Peczynski C, Boreland W, et al. ECP versus ruxolitinib in steroid-refractory chronic GVHD - a retrospective study by the EBMT transplant complications working party. Bone Marrow Transplant. 2024;59(3):380–386. doi: 10.1038/s41409-023-02174-2
  • Major-Monfried H, Renteria AS, Pawarode A, et al. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood. 2018;131(25):2846–2855. doi: 10.1182/blood-2018-01-822957
  • Tian L, Wu Y, Choi HJ, et al. S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission. Cell Mol Immunol. 2022;19(11):1235–1250. doi: 10.1038/s41423-022-00921-x
  • Copsel SN, Lightbourn CO, Barreras H, et al. BET bromodomain inhibitors which permit treg function enable a combinatorial strategy to suppress GVHD in pre-clinical allogeneic HSCT. Front Immunol. 2019;9:3104. doi: 10.3389/fimmu.2018.03104
  • Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the mount sinai acute GVHD international consortium. Biol Blood Marrow Transplant. 2016;22(1):4–10. doi: 10.1016/j.bbmt.2015.09.001
  • Sun Y, Wang Y, Toubai T, et al. BET bromodomain inhibition suppresses graft-versus-host disease after allogeneic bone marrow transplantation in mice. Blood. 2015Apr 23;125(17):2724–2728.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.