Humoral Immunodeficiency in CLL and Therapy With Subcutaneous Ig

Summary

Patients with chronic lymphocytic leukemia (CLL) are at increased risk of infections as compared to age matched controls, with infections being a major cause of morbidity and mortality. Previous studies have shown that patients with CLL have both hypogammaglobinemia and impaired humoral immunity as defined by vaccine responses to both polysaccharide and peptide antigens. Attempts at decreasing infections in CLL have included therapy with prophylactic antibiotics and intravenous immunoglobulin. In general clinical practice and in previous studies, patients have started IV immunoglobulin replacement therapy if they have a history of serious infection or hypogammaglobinemia (defined as Immunoglobulin G below 500-600 g/dL), but vaccine responses have not been evaluated. This study will identify CLL patients with humoral immunodeficiency by checking both Ig levels and vaccines responses. In patients with impaired humoral immunity, the investigators will use subcutaneous immunoglobulin replacement to show this intervention will increase Ig levels, protective antibody titers, and be well tolerated.

Timeline

Start

2018-11-05

Primary completion

2020-07-03

Completion

2020-07-03

Publications

• Background Twomey JJ. Infections complicating multiple myeloma and chronic lymphocytic leukemia. Arch Intern Med. 1973 Oct;132(4):562-5. No abstract available.
• Background Oscier D, Dearden C, Eren E, Fegan C, Follows G, Hillmen P, Illidge T, Matutes E, Milligan DW, Pettitt A, Schuh A, Wimperis J; British Committee for Standards in Haematology. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia. Br J Haematol. 2012 Dec;159(5):541-64. doi: 10.1111/bjh.12067. Epub 2012 Oct 11. No abstract available.
• Background Lachance S, Christofides AL, Lee JK, Sehn LH, Ritchie BC, Shustik C, Stewart DA, Toze CL, Haddad E, Vinh DC. A Canadian perspective on the use of immunoglobulin therapy to reduce infectious complications in chronic lymphocytic leukemia. Curr Oncol. 2016 Feb;23(1):42-51. doi: 10.3747/co.23.2810. Epub 2016 Feb 18.
• Background Chapel H, Dicato M, Gamm H, Brennan V, Ries F, Bunch C, Lee M. Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a comparison of two dose regimes. Br J Haematol. 1994 Sep;88(1):209-12. doi: 10.1111/j.1365-2141.1994.tb05002.x.
• Background Dicato M, Chapel H, Gamm H, Lee M, Ries F, Marichal S, Wirth C, Griffith H, Brennan V. Use of intravenous immunoglobulin in chronic lymphocytic leukemia. A brief review. Cancer. 1991 Sep 15;68(6 Suppl):1437-9. doi: 10.1002/1097-0142(19910915)68:6+3.0.co;2-h.
• Background Molica S, Musto P, Chiurazzi F, Specchia G, Brugiatelli M, Cicoira L, Levato D, Nobile F, Carotenuto M, Liso V, Rotoli B. Prophylaxis against infections with low-dose intravenous immunoglobulins (IVIG) in chronic lymphocytic leukemia. Results of a crossover study. Haematologica. 1996 Mar-Apr;81(2):121-6.
• Background Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD006501. doi: 10.1002/14651858.CD006501.pub2.
• Background Dhalla F, Lucas M, Schuh A, Bhole M, Jain R, Patel SY, Misbah S, Chapel H. Antibody deficiency secondary to chronic lymphocytic leukemia: Should patients be treated with prophylactic replacement immunoglobulin? J Clin Immunol. 2014 Apr;34(3):277-82. doi: 10.1007/s10875-014-9995-5. Epub 2014 Feb 21.
• Background Ueda M, Berger M, Gale RP, Lazarus HM. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation. Blood Rev. 2018 Mar;32(2):106-115. doi: 10.1016/j.blre.2017.09.003. Epub 2017 Sep 19.
• Background Sanchez-Ramon S, Dhalla F, Chapel H. Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy. Front Immunol. 2016 Aug 22;7:317. doi: 10.3389/fimmu.2016.00317. eCollection 2016.
• Background Friman V, Winqvist O, Blimark C, Langerbeins P, Chapel H, Dhalla F. Secondary immunodeficiency in lymphoproliferative malignancies. Hematol Oncol. 2016 Sep;34(3):121-32. doi: 10.1002/hon.2323. Epub 2016 Jul 12.
• Background Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia; Gale RP, Chapel HM, Bunch C, Rai KR, Foon K, Courter SG, Tait D. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. N Engl J Med. 1988 Oct 6;319(14):902-7. doi: 10.1056/NEJM198810063191403.
• Background Looney RJ, Huggins J. Use of intravenous immunoglobulin G (IVIG). Best Pract Res Clin Haematol. 2006;19(1):3-25. doi: 10.1016/j.beha.2005.01.032.
• Background Berger M. Adverse effects of IgG therapy. J Allergy Clin Immunol Pract. 2013 Nov-Dec;1(6):558-66. doi: 10.1016/j.jaip.2013.09.012. Epub 2013 Oct 31.
• Background Gardulf A. Immunoglobulin treatment for primary antibody deficiencies: advantages of the subcutaneous route. BioDrugs. 2007;21(2):105-16. doi: 10.2165/00063030-200721020-00005.
• Background Lingman-Framme J, Fasth A. Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: an evidence-based review. Drugs. 2013 Aug;73(12):1307-19. doi: 10.1007/s40265-013-0094-3.
• Background Compagno N, Cinetto F, Semenzato G, Agostini C. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients. Haematologica. 2014 Jun;99(6):1101-6. doi: 10.3324/haematol.2013.101261. Epub 2014 Mar 28.
• Background Vacca A, Melaccio A, Sportelli A, Solimando AG, Dammacco F, Ria R. Subcutaneous immunoglobulins in patients with multiple myeloma and secondary hypogammaglobulinemia: a randomized trial. Clin Immunol. 2018 Jun;191:110-115. doi: 10.1016/j.clim.2017.11.014. Epub 2017 Nov 28.
• Mustafa SS, Jamshed S, Vadamalai K, Ramsey A. Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia. PLoS One. 2021 Oct 15;16(10):e0258529. doi: 10.1371/journal.pone.0258529. eCollection 2021.

Drugs

Indications