New investigational drugs for Steroid-Refractory Acute Graft-versus-Host disease: a review of the literature

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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Zeiser R, Blazar BR. Acute Graft-versus-Host Disease — Biologic Process, Prevention, and Therapy. New England Journal of Medicine. 377(22):2167–79 (2017).
   PubMed Web of Science ®Google Scholar
• 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. Biology of Blood and Marrow Transplantation.11(12):945–56 (2005).
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Westin JR, Saliba RM, De Lima M, et al. Steroid-Refractory Acute GVHD: Predictors and Outcomes. Advances in Hematology.2011:1–8 (2011).
   Google Scholar
• Przepiorka D, Luo L, Subramaniam S, et al. FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease. Oncologist. 25(2):e328–e34 (2020).
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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. Epub 20221109. doi: 10.1038/s41409-022-01860-x.
   PubMed Web of Science ®Google Scholar
• 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. Transplant Cell Ther. 2022;28(5):261 e1- e7.
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Zhang H, Chen R, Cheng J, Jin N, Chen B. Systematic review and meta-analysis of prospective studies for ECP treatment in patients with steroid-refractory acute GVHD. Patient Prefer Adherence. 9:105–11 (2019).
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Zeiser R, Von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, et al. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. New England Journal of Medicine. 2020;382(19):1800–10.
   PubMed Web of Science ®Google Scholar
• Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, et al. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. New England Journal of Medicine. 2021;385(3):228–38.
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Abedin S, Rashid N, Schroeder M, Romee R, Nauffal M, Alhaj Moustafa 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):429–32.
   PubMed Web of Science ®Google Scholar
• 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. 23(1):172 (2017).
   PubMed Web of Science ®Google Scholar
• Li AC-W, Dong C, Tay S-T, Ananthakrishnan A, Ma KS-K. Vedolizumab for acute gastrointestinal graft-versus-host disease: A systematic review and meta-analysis. Frontiers in Immunology.13 (2022).
   Google Scholar
• Mehta RS, Saliba RM, Jan A, Shigle TL, Wang E, Nieto Y, et al. Vedolizumab for Steroid Refractory Lower Gastrointestinal Tract Graft-Versus-Host Disease. Transplant Cell Ther. 27(3):272 e1- e5 (2021).
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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. 10.3389/fimmu.2023.1241068
   PubMed Web of Science ®Google Scholar
• Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, 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
   PubMed Web of Science ®Google Scholar
• Ball LM, Bernardo ME, Roelofs H, van Tol MJ, Contoli B, Zwaginga JJ, 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):501–9.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, et al. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009;43(3):245–51.
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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. 15(1):2–8. (2013).
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Malard F, Loschi M, Huynh A, Cluzeau T, Guenounou S, Legrand F, 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;62:102111.10.1016/j.eclinm.2023.102111
   PubMedGoogle Scholar
• 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. Epub 20180615. doi: 10.1016/j.bbmt.2018.06.002.
   PubMed Web of Science ®Google Scholar
• van Oosterhout YV, van Emst L, Schattenberg AV, Tax WJ, Ruiter DJ, Spits H, 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):3693–701.
   PubMed Web of Science ®Google Scholar
• 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. Epub 20181103. doi: 10.1016/j.bbmt.2018.10.020. PubMed PMID: 30399420; PubMed Central PMCID: PMC6595479.
   PubMed Web of Science ®Google Scholar
• 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. Epub 20211123. doi: 10.1038/s41409-021-01529-x. PubMed PMID: 34815518; PubMed Central PMCID: PMC8825705.
   PubMed Web of Science ®Google Scholar
• 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. Epub 20230925. doi: 10.1038/s41409-023-02110-4. PubMed PMID: 37749187.
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• Hu X, Wang X, Xue X. Therapeutic perspectives of CD26 inhibitors in Imune-mediated diseases. Molecules. 2022;27(14):4498. doi: 10.3390/molecules27144498
   PubMed Web of Science ®Google Scholar
• Bacigalupo A, Deeg HJ, Caballero D, Gualandi F, Raiola AM, Varaldo R, 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-.
   Web of Science ®Google Scholar
• Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther. 2006;8 Suppl 2(Suppl 2):S3.
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Drobyski WR, Pasquini M, Kovatovic K, et al.. Tocilizumab for the Treatment of Steroid Refractory Graft-versus-Host Disease. Biology of Blood and Marrow Transplantation. 2011;17(12):1862–1868. doi: 10.1016/j.bbmt.2011.07.001
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Magenau JM, Goldstein SC, Peltier D, Soiffer RJ, Braun T, Pawarode A, et al. alpha(1)-Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease. Blood. 2018;131(12):1372–9.
   PubMed Web of Science ®Google Scholar
• Dudakov JA, Hanash AM, van den Brink MR. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. 2015;33:747–85.
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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. 29(8), 509 e1- e8 (2023).
   PubMedGoogle Scholar
• 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. 59(3),380–6 (2024).
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar