2,877
Views
1
CrossRef citations to date
0
Altmetric
Review

Antibody based therapeutics for autoimmune hemolytic anemia

, &
Pages 1227-1237 | Received 11 Jul 2023, Accepted 20 Oct 2023, Published online: 01 Nov 2023

References

  • Berentsen S, Barcellini W. Autoimmune Hemolytic Anemias. N Engl J Med. 2021 Oct 7;385(15):1407–1419. doi: 10.1056/NEJMra2033982.
  • Barcellini W, Fattizzo B. Strategies to overcome the diagnostic challenges of autoimmune hemolytic anemias. Expert Rev Hematol. 2023 Jul;16(7):515–524. doi: 10.1080/17474086.2023.2216930
  • Barcellini W, Fattizzo B. How I treat warm autoimmune hemolytic anemia. Blood. 2021 Mar 11;137(10):1283–1294. Erratum in: Blood. 2023 Jan 26;141(4):438-439. doi: 10.1182/blood.2019003808
  • Barcellini W, Fattizzo B, Zaninoni A, et al. Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood. 2014 Nov 6;124(19):2930–2936. doi: 10.1182/blood-2014-06-583021.
  • Barcellini W, Zaninoni A, Fattizzo B, et al. Predictors of refractoriness to therapy and healthcare resource utilization in 378 patients with primary autoimmune hemolytic anemia from eight Italian reference centers. Am J Hematol. 2018 Sep;93(9):E243–E246. doi: 10.1002/ajh.25212
  • Wang Z, Bo L, Xu Y, et al. Features of serum complement C3 and C4 levels in autoimmune hemolytic anemia patients. Int J Lab Hematol. 2021;43(5):1154–1158. doi: 10.1111/ijlh.13469
  • Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022 Jul;36(7):1703–1719. doi: 10.1038/s41375-022-01613-1
  • Jäger U, Barcellini W, Broome CM, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: recommendations from the first international consensus meeting. Blood Rev. May 2020;41:100648. doi: 10.1016/j.blre.2019.100648.
  • Petz LD, Garratty G. Drug-induced haemolytic anemia. Clin Haematol. 1975 Feb;4(1):181–197. doi: 10.1016/S0308-2261(21)00631-7
  • Reynaud Q, Durieu I, Dutertre M, et al. Efficacy and safety of rituximab in auto-immune hemolytic anemia: a meta-analysis of 21 studies. Autoimmun Rev. 2015 Apr;14(4):304–313. doi: 10.1016/j.autrev.2014.11.014
  • Ho G, Brunson A, Keegan THM, et al. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with autoimmune hemolytic anemia. Blood Cells Mol Dis. 2020 Mar;81:102388.
  • Fattizzo B, Cantoni S, Giannotta JA, et al. Efficacy and safety of cyclosporine a treatment in autoimmune cytopenias: the experience of two Italian reference centers. Ther Adv Hematol. 2022 May 14;13:20406207221097780. doi: 10.1177/20406207221097780
  • Berentsen S, Barcellini W, Longo DL. Autoimmune Hemolytic Anemias. N Engl J Med. 2021 Oct 7;385(15):1407–1419. doi: 10.1056/NEJMra2033982
  • Berentsen S. How I treat cold agglutinin disease. Blood. 2021 Mar 11;137(10):1295–1303. doi: 10.1182/blood.2019003809
  • Röth A, Hüttmann A, Rother RP, et al. Long-term efficacy of the complement inhibitor eculizumab in cold agglutinin disease. Blood. 2009 Apr 16; 113(16):3885–3886. doi: 10.1182/blood-2009-01-196329
  • Röth A, Bommer M, Hüttmann A, et al. Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial. Blood Adv. 2018 Oct 9; 2(19):2543–2549. doi: 10.1182/bloodadvances.2018024190
  • Ma K, Caplan S. Refractory IgG warm autoimmune hemolytic anemia treated with eculizumab: a novel application of anticomplement therapy. Case Rep Hematol. 2016;2016:9181698. doi: 10.1155/2016/9181698
  • Roth A, Barcellini W, D’Sa S, et al. Complement C1s inhibition with sutimlimab results in durable response in cold agglutinin disease: CARDINAL study 1-year interim follow-up results. Haematologica. 2022 Jul 1; 107(7):1698–1702. doi: 10.3324/haematol.2021.279812
  • Röth A, Berentsen S, Barcellini W, et al. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022 Sep 1; 140(9):980–991. doi: 10.1182/blood.2021014955
  • Fattizzo B, Zaninoni A, Gianelli U, et al. Prognostic impact of bone marrow fibrosis and dyserythropoiesis in autoimmune hemolytic anemia. Am J Hematol. 2018 Aug;93(4):E88–E91. doi: 10.1002/ajh.25020
  • Fattizzo B, Pasquale R, Carpenedo M, et al. Bone marrow characteristics predict outcome in a multicenter cohort of primary immune thrombocytopenia patients treated with thrombopoietin analogs. Haematologica. 2019 Oct;104(10):e470–e473. doi: 10.3324/haematol.2019.216804
  • Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994 Jan 15;83(2):435–445. doi: 10.1182/blood.V83.2.435.435
  • Stasi R. Rituximab in autoimmune hematologic diseases: not just a matter of B cells. Semin Hematol. 2010 Apr;47(2):170–179. doi: 10.1053/j.seminhematol.2010.01.010
  • Motto DG, Williams JA, Boxer LA. Rituximab for refractory childhood autoimmune hemolytic anemia. Isr Med Assoc J. 2002 Nov;4(11):1006–1008.
  • Narat S, Gandla J, Hoffbrand AV, et al. Rituximab in the treatment of refractory autoimmune cytopenias in adults. Haematologica. 2005 Sep;90(9):1273–1274.
  • Bussone G, Ribeiro E, Dechartres A, et al. Efficacy and safety of rituximab in adults’ warm antibody autoimmune haemolytic anemia: retrospective analysis of 27 cases. Am J Hematol. 2009 Mar;84(3):153–157. doi: 10.1002/ajh.21341
  • Birgens H, Frederiksen H, Hasselbalch HC, et al. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol. 2013 Nov;163(3):393–399. doi: 10.1111/bjh.12541
  • Maung SW, Leahy M, O’Leary HM, et al. A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia. Br J Haematol. 2013 Oct;163(1):118–122. doi: 10.1111/bjh.12486
  • Michel M, Terriou L, Roudot-Thoraval F, et al. A randomized and double-blind controlled trial evaluating the safety and efficacy of rituximab for warm auto-immune hemolytic anemia in adults (the RAIHA study). Am J Hematol. 2017 Jan;92(1):23–27. doi: 10.1002/ajh.24570
  • Gutiérrez Jomarrón I, López Rubio M, Arias MM, et al. Autoimmune haemolytic anaemias: a retrospective study of 93 patients. Med Clin. 2020 May 8;154(9):331–337. English, Spanish. doi: 10.1016/j.medcli.2019.06.024
  • Berentsen S, Ulvestad E, Gjertsen BT, et al. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood. 2004 Apr 15; 103(8):2925–2928. doi: 10.1182/blood-2003-10-3597
  • Schöllkopf C, Kjeldsen L, Bjerrum OW, et al. Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients. Leuk Lymphoma. 2006 Feb;47(2):253–260. doi: 10.1080/10428190500286481
  • Berentsen S, Randen U, Vågan AM, et al. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010 Oct 28; 116(17):3180–3184. doi: 10.1182/blood-2010-06-288647
  • Berentsen S, Randen U, Oksman M, et al. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood. 2017 Jul 27; 130(4):537–541. doi: 10.1182/blood-2017-04-778175
  • Berentsen S, Barcellini W, D’Sa S, et al. Cold agglutinin disease revisited: a multinational, observational study of 232 patients. Blood. 2020 Jul 23; 136(4):480–488. doi: 10.1182/blood.2020005674
  • Zaja F, Iacona I, Masolini P, et al. B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia. Haematologica. 2002 Feb;87(2):189–195. Erratum in: Haematologica 2002 Mar;87(3):336.
  • Zecca M, Nobili B, Ramenghi U, et al. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood. 2003 May 15; 101(10):3857–3861. doi: 10.1182/blood-2002-11-3547
  • Dierickx D, Verhoef G, Van Hoof A, et al. Rituximab in auto-immune haemolytic anaemia and immune thrombocytopenic purpura: a Belgian retrospective multicentric study. J Intern Med. 2009 Nov;266(5):484–491. doi: 10.1111/j.1365-2796.2009.02126.x
  • Peñalver FJ, Alvarez-Larrán A, Díez-Martin JL, et al. Multi-institutional retrospective study on the use of rituximab in refractory AIHA. Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia. Ann Hematol. 2010 Nov;89(11):1073–1080. doi: 10.1007/s00277-010-0997-y
  • Barcellini W, Zaja F, Zaninoni A, et al. Sustained response to low-dose rituximab in idiopathic autoimmune hemolytic anemia. Eur J Haematol. 2013 Dec;91(6):546–551. doi: 10.1111/ejh.12199
  • Ducassou S, Leverger G, Fernandes H, et al. Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study. Br J Haematol. 2017 Jun;177(5):751–758. doi: 10.1111/bjh.14627
  • Chao SH, Chang YL, Yen JC, et al. Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis. Exp Hematol Oncol. 2020 Apr 15;9(1):6. doi: 10.1186/s40164-020-00163-5
  • Lee EJ, Kueck B. Rituxan in the treatment of cold agglutinin disease. Blood. 1998;92(9):3490–3491. doi: 10.1182/blood.V92.9.3490
  • A study of efficacy and safety of ianalumab in Previously treated patients with warm autoimmune hemolytic anemia (VAYHIA). ClinicalTrials.Gov Identifier: NCT05648968. [ Updated 2023 May 25; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05648968
  • Xu ZZ, Zhao BB, Xiong H, et al. Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance. Int J Hematol. 2015 Oct;102(4):394–400. doi: 10.1007/s12185-015-1851-8
  • An open-label study of povetacicept in subjects with autoimmune cytopenias (RUBY-4). ClinicalTrials.Gov Identifier: NCT05757570. [ Updated 2023 Mar 7; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05757570
  • A study of obexelimab in patients with warm autoimmune hemolytic anemia (SApHiare). ClinicalTrials.Gov Identifier: NCT05786573. [ Updated 2023 May 19; cited 2023 Jul 5]. Available from: https://clinicaltrials.gov/study/NCT05786573
  • Jalink M, Berentsen S, Castillo JJ, et al. Effect of ibrutinib treatment on hemolytic anemia and acrocyanosis in cold agglutinin disease/cold agglutinin syndrome. Blood. 2021 Nov 18; 138(20):2002–2005. doi: 10.1182/blood.2021012039
  • Ibrutinib in steroid refractory autoimmune hemolytic anemia (ISRAEL). ClinicalTrials.Gov Identifier: NCT03827603. [ Updated 2020 Jan 10; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT03827603
  • Efficacy, safety and pharmacokinetics of Rilzabrutinib in patients with warm autoimmune hemolytic anemia (wAIHA). ClinicalTrials.Gov Identifier: NCT05002777. Updated 2023 May 31; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05002777
  • Kuter DJ, Rogers KA, Boxer MA, et al. Fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia: phase 2, multicenter, open-label study. Am J Hematol. 2022 Jun 1; 97(6):691–699. doi: 10.1002/ajh.26508
  • Pasquale R, Giannotta JA, Barcellini W, et al. Bortezomib in autoimmune hemolytic anemia and beyond. Ther Adv Hematol. 2021 Nov 12;12:20406207211046428. doi: 10.1177/20406207211046428
  • Rossi G, Gramegna D, Paoloni F, et al. Short course of bortezomib in anemic patients with relapsed cold agglutinin disease: a phase 2 prospective GIMEMA study. Blood. 2018;132(5):547–550. doi: 10.1182/blood-2018-03-835413
  • Schuetz C, Hoenig M, Moshous D, et al. Daratumumab in life-threatening autoimmune hemolytic anemia following hematopoietic stem cell transplantation. Blood Adv. 2018 Oct 9; 2(19):2550–2553. doi: 10.1182/bloodadvances.2018020883
  • Cooling L, Hugan S. Daratumumab in combination with standard treatment for autoimmune hemolytic anemia in a pediatric patient. Transfusion. 2019 Dec;59(12):3801–3802. doi: 10.1111/trf.15539
  • Blennerhassett R, Sudini L, Gottlieb D, et al. Post-allogeneic transplant Evans syndrome successfully treated with daratumumab. Br J Haematol. 2019 Oct;187(2):e48–e51. doi: 10.1111/bjh.16171
  • Even-Or E, Naser Eddin A, Shadur B, et al. Successful treatment with daratumumab for post-HSCT refractory hemolytic anemia. Pediatr Blood Cancer. 2020 Jan;67(1):e28010. doi: 10.1002/pbc.28010
  • Rieger MJ, Stolz SM, Ludwig S, et al. Daratumumab in rituximab-refractory autoimmune haemolytic anaemia. Br J Haematol. 2021 Sep;194(5):931–934. doi: 10.1111/bjh.17655
  • Jain A, Gupta DK. Daratumumab for refractory warm autoimmune hemolytic anemia. Ann Hematol. 2021 May;100(5):1351–1353. doi: 10.1007/s00277-020-04063-w
  • Tomkins O, Berentsen S, Arulogun S, et al. Daratumumab for disabling cold agglutinin disease refractory to B-cell directed therapy. Am J Hematol. 2020 Jul 11;95(10). doi: 10.1002/ajh.25932
  • Zaninoni A, Giannotta JA, Gallì A, et al. The immunomodulatory effect and clinical efficacy of daratumumab in a patient with cold agglutinin disease. Front Immunol. 2021 Mar 1;12:649441. doi: 10.3389/fimmu.2021.649441
  • Driouk L, Schmitt R, Peters A, et al. Daratumumab therapy for post-HSCT immune-mediated cytopenia: experiences from two pediatric cases and review of literature. Mol Cell Pediatr. 2021 Apr 29; 8(1):5. doi: 10.1186/s40348-021-00114-y
  • Safety, pharmacokinetics, and efficacy of subcutaneous isatuximab in adults with warm autoimmune hemolytic anemia (wAIHA). ClinicalTrials.Gov Identifier: NCT04661033. [ Updated 2023 Mar 13; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04661033
  • Gupta N, Wang ES. Long-term response of refractory primary cold agglutinin disease to eculizumab therapy. Ann Hematol. 2014 Feb;93(2):343–344. doi: 10.1007/s00277-013-1800-7
  • Shapiro R, Chin-Yee I, Lam S. Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti-pr specificity. Clin Case Rep. 2015 Nov;3(11):942–944. doi: 10.1002/ccr3.399
  • Makishima K, Obara N, Ishitsuka K, et al. High efficacy of eculizumab treatment for fulminant hemolytic anemia in primary cold agglutinin disease. Ann Hematol. 2019 Apr;98(4):1031–1032. doi: 10.1007/s00277-018-3521-4
  • Herbreteau L, Le Calloch R, Arnaud B, et al. Eculizumab, a real-life successful treatment for refractory cold agglutinin-mediated auto-immune hemolytic anemia secondary to lymphoproliferative disorders. Ann Hematol. 2021 Aug;100(8):2105–2106. doi: 10.1007/s00277-021-04557-1
  • Dawudi Y, Federici L, Debus J, et al. Cold agglutinin disease secondary to severe SARS-CoV-2 treated with eculizumab. BMJ Case Rep. 2022 Apr 29; 15(4):e242937. doi: 10.1136/bcr-2021-242937
  • Chao MP, Hong J, Kunder C, et al. Refractory warm IgM-mediated autoimmune hemolytic anemia associated with Churg-Strauss syndrome responsive to eculizumab and rituximab. Am J Hematol. 2015 Jan;90(1):78–81. doi: 10.1002/ajh.23791
  • Neave L, Wilson AJ, Lissack M, et al. Severe refractory idiopathic warm autoimmune haemolytic anaemia responsive to complement inhibition with eculizumab. BMJ Case Rep. 2018 Dec 13; 11(1):e226429. doi: 10.1136/bcr-2018-226429
  • Gauchy AC, Hentzien M, Wynckel A, et al. Efficacy of eculizumab in refractory life-threatening warm autoimmune hemolytic anemia associated with chronic myelomonocytic leukemia. Clin Case Rep. 2020 Aug 17;8(12):2641–2644. doi: 10.1002/ccr3.3250
  • Tahhan F, Huynh B, Xu P. Novel monoclonal antibody therapy in a patient with treatment-refractory warm autoimmune hemolytic anemia. Cureus. 2022 Jun 17;14(6):e26051. doi: 10.7759/cureus.26051
  • Jackson EM, Harper S, Webb GJ, et al. Severe refractory warm autoimmune haemolytic anaemia after the SARS-CoV-2 pfizer-BioNTech vaccine (BNT162b2 mRNA) managed with emergency splenectomy and complement inhibition with eculizumab. BMJ Case Rep. 2022 Aug 31; 15(8):e250774. doi: 10.1136/bcr-2022-250774
  • Shi J, Rose EL, Singh A, et al. TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins. Blood. 2014 Jun 26; 123(26):4015–4022. doi: 10.1182/blood-2014-02-556027
  • Jäger U, D’Sa S, Schörgenhofer C, et al. Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial. Blood. 2019 Feb 28; 133(9):893–901. doi: 10.1182/blood-2018-06-856930
  • Röth A, Barcellini W, D’Sa S, et al. Sutimlimab in cold agglutinin disease. N Engl J Med. 2021 Apr 8;384(14):1323–1334. doi: 10.1056/NEJMoa2027760.
  • Tvedt THA, Steien E, Øvrebø B, et al. Sutimlimab, an investigational C1s inhibitor, effectively prevents exacerbation of hemolytic anemia in a patient with cold agglutinin disease undergoing major surgery. Am J Hematol. 2022 Feb 1;97(2):E51–E54. doi: 10.1002/ajh.26409
  • Röth A, Berentsen S, Barcellini W, et al. Sustained efficacy of sutimlimab, a complement c1s inhibitor, in patients with cold agglutinin disease: results from part b of the phase 3 cadenza study. Poster presented at EHA, Frankfurt, 2023
  • Röth A, Barcellini W, Tvedt THA, et al. Sutimlimab improves quality of life in patients with cold agglutinin disease: results of patient-reported outcomes from the CARDINAL study. Ann Hematol. 2022 Oct;101(10):2169–2177. doi: 10.1007/s00277-022-04948-y
  • Gertz M, Roman E, Fattizzo B, et al. Inhibition of C3 with APL-2 controls haemolysis and increases haemoglobin levels in subjects with autoimmune haemolytic anaemia (AIHA). EHA Lib. 2019;3:S899. doi: 10.1097/01.HS9.0000561876.96057.48
  • A study to evaluate the efficacy and safety of pegcetacoplan in patients with cold agglutinin disease (CAD). ClinicalTrials.Gov Identifier: NCT05096403. [ Updated 2023 Jun 2; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05096403
  • Basket study to assess efficacy, safety and PK of iptacopan (LNP023) in autoimmune benign hematological disorders. ClinicalTrials.Gov Identifier: NCT05086744. [ Updated 2023 Jul 3; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05086744
  • Barcellini W, Zaninoni A, Giannotta JA, et al. New insights in autoimmune hemolytic anemia: from pathogenesis to therapy stage 1. J Clin Med. 2020 Nov 27;9(12):3859. doi: 10.3390/jcm9123859
  • Garg M, Agarwal S, Altohami M. A single dose of eculizumab terminated life-threatening haemolysis in idiopathic IgM-mediated warm autoimmune haemolytic anaemia: a case report. Br J Haematol. 2022 Apr;197(2):e28–e31. doi: 10.1111/bjh.18011
  • Study to assess the safety, tolerability, efficacy and PK of APL-2 in patients with warm type autoimmune hemolytic anemia (wAIHA) or cold agglutinin disease (CAD). ClinicalTrials.Gov Identifier: NCT03226678. [ Updated 2023 Apr 3; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT03226678
  • Safety, tolerability, pharmacokinetics and pharmacodynamics of ANX005 in participants with warm autoimmune hemolytic anemia (wAIHA). ClinicalTrials.Gov Identifier: NCT04691570. [ Updated 2023 Mar 6; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04691570
  • A safety study of SYNT001 in participants with warm autoimmune hemolytic anemia (WAIHA). ClinicalTrials.Gov Identifier: NCT03075878. [ Updated 2020 May 13; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT03075878
  • To assess the efficacy and safety of RVT-1401 in the treatment of warm autoimmune hemolytic anemia (ASCEND-WAIHA). ClinicalTrials.Gov Identifier: NCT04253236. [ Updated 2022 Jul 28; cited 2023 Jul 5]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04253236