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Review

Managing hypogammaglobulinemia in patients treated with CAR-T-cell therapy: key points for clinicians

ORCID Icon, , & ORCID Icon
Pages 305-320 | Received 22 Dec 2021, Accepted 05 Apr 2022, Published online: 11 Apr 2022

References

  • Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with b-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–448.
  • Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large b-cell lymphoma. N Engl J Med. 2019;380:45–56.
  • Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel car t-cell therapy in refractory large b-cell lymphoma. N Engl J Med. 2017;377:2531–2544.
  • Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396:839–852.
  • Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331–1342.
  • Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384:705–716.
  • Vitale C, Strati P. CAR T-cell therapy for B-cell non-hodgkin lymphoma and chronic lymphocytic leukemia: clinical trials and real-world experiences. Front Oncol. 2020;10:849.
  • Yamamoto TN, Kishton RJ, Restifo NP. Developing neoantigen-targeted T cell-based treatments for solid tumors. Nat Med. 2019;25:1488–1499.
  • Maldini CR, Ellis GI, Riley JL. CAR T cells for infection, autoimmunity and allotransplantation. Nat Rev Immunol. 2018;18:605–616.
  • June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73.
  • Sadelain M, Rivière I, Riddell S. Therapeutic T cell engineering. Nature. 2017;545:423–431.
  • Rafiq S, Hackett CS, Brentjens RJ. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat Rev Clin Oncol. 2020;17:147–167.
  • Meir J, Abid MA, Abid MB. State of the CAR-T: risk of infections with chimeric antigen receptor T-cell therapy and determinants of SARS-CoV-2 vaccine responses. Transplant Cell Ther. 2021;27:973–987. DOI:https://doi.org/10.1016/j.jtct.2021.09.016.
  • Gudiol C, Lewis RE, Strati P, et al. Chimeric antigen receptor T-cell therapy for the treatment of lymphoid malignancies: is there an excess risk for infection? Lancet Haematol. 2021;8:e216–e228.
  • Hill JA, Seo SK. How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood. 2020;136:925–935. DOI:https://doi.org/10.1182/blood.2019004000.
  • Fried S, Avigdor A, Bielorai B, et al. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019 2019 5410;54:1643–1650. DOI:https://doi.org/10.1038/s41409-019-0487-3.
  • Wang L, Hong R, Zhou L, et al. new-onset severe cytopenia after CAR-T cell therapy: analysis of 76 patients with relapsed or refractory acute lymphoblastic leukemia. Front Oncol. 2021;11:2433.
  • Rejeski K, Perez Perez A, Sesques P, et al. CAR-HEMATOTOX: a model for CAR T-cell related hematological toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499–2513.
  • Juluri KR, Wu V, Voutsinas JM, et al. Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy. Blood Adv. 2021;130:2295–2306.
  • Hill JA, Li D, Hay KA, et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood. 2018;131:121–130. DOI:https://doi.org/10.1182/blood-2017-07-793760
  • Park JH, Romero FA, Taur Y, et al. Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory b-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells. Clin Infect Dis. 2018;67:533–540.
  • Haidar G, Dorritie K, Farah R, et al. Invasive mold infections after chimeric antigen receptor-modified t-cell therapy: a case series, review of the literature, and implications for prophylaxis. Clin Infect Dis. 2020;71:672–676.
  • Hay KA, Hanafi L-A, Li D, et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor–modified T-cell therapy. Blood. 2017;130:2295–2306.
  • Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625–638.
  • Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016;127:3321–3330.
  • Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: mechanisms, manifestations and management. Blood Rev. 2019;34:45–55.
  • Kochenderfer JN, Dudley ME, Feldman SA, et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells. Blood. 2012;119:2709–2720.
  • Carpenter RO, Evbuomwan MO, Pittaluga S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048–2060.
  • Baird JH, Epstein DJ, Tamaresis JS, et al. Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma. Blood Adv. 2021;5:143–155.
  • Morbach H, Eichhorn EM, Liese JG, et al. Reference values for B cell subpopulations from infancy to adulthood. Clin Exp Immunol. 2010;162:271–279.
  • Logue JM, Zucchetti E, Bachmeier CA, et al. Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. Haematologica. 2020; 106. 2019 . 238634.
  • Walti CS, Krantz EM, Maalouf J, et al. Antibodies to vaccine-preventable infections after CAR-T-cell therapy for B-cell malignancies. JCI Insight. 2021. DOI:https://doi.org/10.1172/jci.insight.146743.
  • Halliley JL, Tipton CM, Liesveld J, et al. Long-lived plasma cells are contained within the CD19−CD38hiCD138+ subset in human bone marrow. Immunity. 2015;43:132–145.
  • Bhoj VG, Arhontoulis D, Wertheim G, et al. Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood. 2016;128:360–370.
  • Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380:1726–1737.
  • Sanz I, Wei C, Jenks SA, et al. Challenges and opportunities for consistent classification of human b cell and plasma cell Populations. Front Immunol. 2019;10:2458.
  • Ueda M, Berger M, Gale RP, et al. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation. Blood Rev. 2018;32:106–115.
  • Kambhampati S, Sheng Y, Huang C-Y, et al. Infectious complications in relapsed refractory multiple myeloma patients after BCMA Car t-cell therapy. Blood Adv. 2021;5:5344–5348. DOI:https://doi.org/10.1182/bloodadvances.2021005020
  • Vora SB, Waghmare A, Englund JA, et al. Infectious complications following CD19 chimeric antigen receptor t-cell therapy for children, adolescents, and young adults. Open Forum Infect Dis. 2020;7:1–9.
  • Wudhikarn K, Palomba ML, Pennisi M, et al. Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma. Blood Cancer J 2020;10DOI:https://doi.org/10.1038/s41408-020-00346-7.
  • Cordeiro A, Bezerra ED, V HA, et al. Late events after treatment with CD19-targeted chimeric antigen receptor modified T cells. Biol Blood Marrow Transplant. 2020;26:26–33. DOI:https://doi.org/10.1016/j.bbmt.2019.08.003
  • Hill JA, Krantz EM, Hay KA, et al. Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy. Blood Adv. 2019;3:3590–3601.
  • Levine JE, Grupp SA, Pulsipher MA, et al. Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia. J Immunother Cancer. 2021;9:e002287.
  • Arnold DE, Maude SL, Callahan CA, et al. Subcutaneous immunoglobulin replacement following CD19-specific chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia in pediatric patients. Pediatr Blood Cancer. 2020;67:1–4.
  • Deyà-Martínez A, Alonso-Saladrigues A, García AP, et al. Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia. Bone Marrow Transplant. 2021;56:376–386.
  • Pasquini MC, Z-h H, Curran K, et al. Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Adv. 2020;4:5414–5424.
  • Josyula S, Pont M, Keane-Candib J, et al. Infectious complications and humoral immunity after BCMA-directed chimeric antigen receptor T-cell therapy in adults with multiple myeloma. Transplant Cell Ther. 2021;27:S345–S346.
  • Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019;20:31–42.
  • Schuster SJ, Svoboda J, Chong EA, et al. chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017 [.Dec 10];377:2545–2554.
  • Hill JA, Giralt S, Torgerson TR, et al. CAR-T – and a side order of IgG, to go? – immunoglobulin replacement in patients receiving CAR-T cell therapy. Blood Rev. 2019;38:100596. DOI:https://doi.org/10.1016/j.blre.2019.100596
  • Pihlgren M, Schallert N, Tougne C, et al. Delayed and deficient establishment of the long-term bone marrow plasma cell pool during early life. Eur J Immunol. 2001;31:939–946.
  • Zhu F, Wei G, Liu Y, et al. Incidence and risk factors associated with infection after chimeric antigen receptor T cell therapy for relapsed/refractory B-cell malignancies. Cell Transplant. 2021;30:1–9.
  • Beyar-Katz O, Kikozashvili N, Bar On Y, et al. Characteristics and recognition of early infections in patients treated with commercial anti-CD19 CAR-T cells. Eur J Haematol. 2021;108:53–60.
  • Strati P, Varma A, Adkins S, et al. Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma. Haematologica. 2021;106:2667–2672.
  • Park JH, Rivière I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–459.
  • Spanjaart AM, Ljungman P, de La Camara R, et al. Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European society for blood and marrow transplantation (EBMT) infectious diseases working party and the European Hemato. Leukemia. 2021;35:3585–3588.
  • Busca A, Salmanton-García J, Corradini P, et al. COVID-19 and CAR-T cells: current challenges and future directions-a report from the EPICOVIDEHA survey by EHA-IDWP. Blood Adv. 2021. DOI:https://doi.org/10.1182/bloodadvances.2021005616.
  • Mikkilineni L, Yates B, Steinberg SM, et al. Infectious complications of CAR T-cell therapy across novel antigen targets in the first 30 days. Blood Adv. 2021;5:5312–5322.
  • Kambhampati S, Fakhri B, Sheng Y, et al. Infectious complications of BCMA-targeted and CD19-targeted chimeric antigen receptor T-cell immunotherapy. Blood. 2020;136:4–5.
  • Wang D, Mao X, Que Y, et al. Viral infection/reactivation during long-term follow-up in multiple myeloma patients with anti-BCMA CAR therapy. Blood Cancer J. 2021;11:5–8.
  • Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1–S46. DOI:https://doi.org/10.1016/j.jaci.2016.09.023.
  • Arnold DE, Maude SL, Callahan CA, et al. Review of indications for immunoglobulin (IG) use: narrowing the gap between supply and demand. J Allergy Clin Immunol. 2019;67:S1–S46.
  • Raanani P, Gafter-Gvili A, Paul M, et al. Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2008; CD006501. DOI:https://doi.org/10.1002/14651858.CD006501.pub2.
  • Raanani P, Gafter-Gvili A, Paul M, et al. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk Lymphoma. 2009;50(5):764–772. DOI:https://doi.org/10.1080/10428190902856824.
  • Bhella S, Majhail NS, Betcher J, et al. Choosing wisely BMT: American society for blood and marrow transplantation and Canadian blood and marrow transplant group’s list of 5 tests and treatments to question in blood and marrow transplantation. Biol Blood Marrow Transplant. 2018;24:909–913.
  • Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2014;136:1186–1205.e78.
  • Kansagra AJ, Frey N V, Bar M, et al. Clinical utilization of chimeric antigen receptor T cells in B cell acute lymphoblastic leukemia: an expert opinion from the European society for blood and marrow transplantation and the American society for blood and marrow transplantation. Biol Blood Marrow Transplant. 2019;25:e76–e85.
  • Yakoub-Agha I, Chabannon C, Bader P, et al. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European society for blood and marrow transplantation (EBMT) and the joint accreditation committee of ISCT and EBMT (JACIE). Haematologica. 2020;105:297–316.
  • Mahmoudjafari Z, Hawks KG, Hsieh AA, et al. American society for blood and marrow transplantation pharmacy special interest group survey on chimeric antigen receptor T cell therapy administrative, logistic, and toxicity management practices in the United States. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2019;25:26–33.
  • Brand A, De Angelis V, Vuk T, et al. Review of indications for immunoglobulin (IG) use: narrowing the gap between supply and demand. Transfus Clin Biol. 2021;28:96–122.
  • Mahadeo KM, Khazal SJ, Abdel-Azim H, et al. Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy. Nat Rev Clin Oncol. 2019;16:45–63.
  • Shalabi H, Gust J, Taraseviciute A, et al. Beyond the storm — subacute toxicities and late effects in children receiving CAR T cells. Nat Rev Clin Oncol. 2021;18:363–378.
  • Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor t cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–1517.
  • Pescovitz MD, Torgerson TR, Ochs HD, et al. Effect of rituximab on human in vivo antibody immune responses. J Allergy Clin Immunol. 2011;128:1295–1302.e5.
  • Berger M. Adverse Effects of IgG Therapy. J Allergy Clin Immunol Pract. 2013;1:558–566.
  • Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin 1 1This review article reflects the opinions of the authors and not necessarily those of the U.S. Food and Drug Administration. Transfus Med Rev. 2003;17:241–251.
  • Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013;27:171–178.
  • Guo Y, Tian X, Wang X, et al. Adverse Effects of Immunoglobulin Therapy. Front Immunol. 2018;9:1299.
  • Bichuetti-Silva DC, Furlan FP, Nobre FA, et al. Immediate infusion-related adverse reactions to intravenous immunoglobulin in a prospective cohort of 1765 infusions. Int Immunopharmacol. 2014;23:442–446.
  • Daniel GW, Menis M, Sridhar G, et al. Immune globulins and thrombotic adverse events as recorded in a large administrative database in 2008 through 2010. Transfusion. 2012;52:2113–2121.
  • Ramírez E, Romero-Garrido JA, López-Granados E, et al. Symptomatic thromboembolic events in patients treated with intravenous-immunoglobulins: results from a retrospective cohort study. Thromb Res. 2014;133:1045–1051.
  • Ammann EM, Jones MP, Link BK, et al. Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy. Blood. 2016;127:200–207.
  • Centers for Disease Control and Prevention (CDC). Renal insufficiency and failure associated with immune globulin intravenous therapy–United States, 1985-1998. MMWR Morb Mortal Wkly Rep. 1999;48:518–521.
  • Daw Z, Padmore R, Neurath D, et al. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis. Transfusion. 2008;48:1598–1601.
  • Scott DE, Epstein JS. Safeguarding immune globulin recipients against hemolysis: what do we know and where do we go? Transfusion. 2015;55:S122–S126.
  • Derman BA, Schlei Z, Parsad S, et al. Changes in intravenous immunoglobulin usage for hypogammaglobulinemia after implementation of a stewardship program. JCO Oncol Pract. 2021;17:e445–e453.
  • Cordonnier C, Einarsdottir S, Cesaro S, et al. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European conference on infections in leukaemia (ECIL 7); Lancet Infect Dis. 2019;19:e200–e212.
  • Mikulska M, Cesaro S, de Lavallade H, et al. Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European conference on infections in leukaemia (ECIL 7); Lancet Infect Dis. 2019;19:e188–e199.
  • Jain T, Bar M, Kansagra AJ, et al. Use of chimeric antigen receptor T cell therapy in clinical practice for relapsed/refractory aggressive B cell non-hodgkin lymphoma: an expert panel opinion from the American society for transplantation and cellular therapy. Biol. Blood Marrow Transplant. Elsevier. 2019;25:2305–2321.
  • https://www.hematology.org/covid-19/ash-astct-covid-19-vaccination-for-hct-and-car-t-cell-recipients .
  • Carpenter PA, Englund JA. How I vaccinate blood and marrow transplant recipients. Blood. 2016;127:2824–2832.
  • nccn.org [Internet]. [cited 2021 Dec 10]. Available from: https://www.nccn.org/docs/default-source/covid-19/2021_covid-19_vaccination_guidance_v4-0.pdf?sfvrsn=b483da2b_70.
  • https://www.cdc.gov/vaccines/covid-19/clinical-considerations/.
  • Walti CS, Loes AN, Shuey K, et al. Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy: a prospective observational study. J Immunother Cancer. 2021;9:e003428. DOI:https://doi.org/10.1136/jitc-2021-003428
  • Dhakal B, Abedin S, Fenske T, et al. Response to SARS-CoV-2 vaccination in patients after hematopoietic cell transplantation and CAR T-cell therapy. Blood. 2021;138:1278–1281.
  • Ram R, Hagin D, Kikozashvilli N, et al. Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients after allogeneic HCT or CD19-based CART therapy—A single-center prospective cohort study. Transplant Cell Ther. 2021;27:788–794. DOI:https://doi.org/10.1016/j.jtct.2021.06.024
  • Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384:238–251.
  • Dougan M, Nirula A, Azizad M, et al. Bamlanivimab plus etesevimab in mild or moderate Covid-19. N Engl J Med. 2021;385:1382–1392.
  • O’Brien MP, Forleo-Neto E, Musser BJ, et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med. 2021;385:1184–1195.
  • FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF REGEN-COV (casirivimab and imdevimab) [Internet]. Available from: https://www.fda.gov/media/145611/download. [Accessed April 8, 2022].
  • FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF BAMLANIVIMAB AND ETESEVIMAB [Internet]. Available from: https://www.fda.gov/media/145802/download. [Accessed April 8, 2022].
  • FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF SOTROVIMAB [Internet]. Available from: https://www.fda.gov/media/149534/download. [Accessed April 8, 2022].
  • Coronavirus (COVID-19) Update: FDA authorizes new long-acting monoclonal antibodies for pre-exposure prevention of COVID-19 in certain individuals [Internet]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-new-long-acting-monoclonal-antibodies-pre-exposure. [Accessed April 8, 2022].
  • Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Recomm reports Morb Mortal Wkly report Recomm reports. 2000;49:1–125, CE1-7.
  • Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2009;15:1143–1238.

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