Secondary Immunodeficiency (SID) in patients with haematological malignancies

Increasing incidence of SID caused by the underlying diseases and therapeutics

Secondary immune deficiencies (SID) are caused by varied mechanisms and are common in patients with haematological malignancies such as chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). In addition, also stem cell transplant is associated with secondary immunodeficiency.

Both the underlying disease and its treatment (e.g. B-cell targeting therapy) contribute to the development of secondary antibody deficiency. Infections remain a major cause of morbidity and mortality. Patients with severe and long-lasting disease are at greater risk.

As it has been shown for primary immunodeficiencies, studies indicate a clinical benefit of immunoglobulin therapy (IgG) as a treatment for secondary immunodeficiency. Thus, guidelines are in support of considering immunoglobulin replacement therapy in selected patients with secondary antibody deficiency.1

Person living with chronic lymphocytic leukaemia

Immunodeficiency in chronic lymphocytic leukaemia (CLL)

CLL is associated with a high rate of infections, accounting for up to 60% of mortality

Up to 80% of CLL patients experience infectious complications at some point during their disease, 20% of them severe/major infections. Up to 60% of overall mortality in CLL is caused by infectious complications. While targeted and biologic therapies have improved overall survival, the proportion of CLL patients dying because of infections has not improved. Both the disease and therapies are associated with the development of immunodeficiencies and hypogammaglobulinaemia.2

Person applying immunoglobulin therapy

Important role of immunoglobulins to treat secondary immunodeficiency

Treatment with immunoglobulins is associated with a significant reduction of infection risk in patients with haematological malignancies and secondary immunodeficiency

Immunoglobulin replacement therapy is efficacious in immune compromised patients with haematological malignancies and after stem cell transplantation. Intravenous infusions or subcutaneous injections of immunoglobulin (IgG) can reduce infection risk and infection frequency. Immunoglobulin therapy is well-tolerated and recommended under certain circumstances by evidence-based guidelines.3

Persons living with Multiple Myeloma

Secondary immunodeficiency in Multiple Myeloma

Multiple Myeloma and its treatments raise the risk of infections

Infections are a substantial cause of death in multiple myeloma. Different chemotherapy regimens and the cumulative dose of corticosteroids are independently associated with increased risk of infection in multiple myeloma. Established and novel therapies and the underlying multiple myeloma disease cause hypogammaglobulinaemia and infection-related deaths to persist. In a study of more than 3,000 patients with multiple myeloma, infections were responsible for 45% of deaths within 6 months of diagnosis.4

Persons living with burden of immune-deficiency after stem cell transplant

The burden of immune-deficiency after stem cell transplant

Infection complications are a major cause of morbidity and mortality in haematopoietic stem cell transplant recipients

Patients undergoing autologous or allogeneic transplant can have pancytopaenia and immunodeficiency from therapy. This may lead to potentially fatal bacterial, fungal, or viral infections such as cytomegalovirus (CMV) and immune complications such as graft-versus-disease (GVHD) following transplantation.
Infection is reported as the primary cause of death in 8% of autologous HCT patients and 17% to 20% of allogeneic HCT recipients.5


Secondary immunodeficiency at the EHA25 virtual congress

The burden of infection in Chronic Lymphocytic Leukaemia and Multiple Myeloma, infection complications of CAR T immunotherapy, recommendations for the use of IgG therapy in these patients

On June 12th, 2020, at the 25th European Hematology Association (EHA) Annual Congress, three medical experts presented the latest advances on how to treat patients with secondary immunodeficiencies (SIDs) associated with haematological malignancies.

The importance of infection control in the management of haematological malignancies

Infection is a major complication in patients with haematological malignancies. Prophylaxis and infection control are key elements in the management of these patients

Prof. Isabella Quinti (Rome, Italy), Dr. Anne Quinquenel (Reims, France) and Prof. Igor-Wolfgang Blau (Berlin, Germany) share their perspective on the importance of secondary immune deficiencies and infections in patients with chronic lymphocytic leukaemia (CLL), multiple myeloma, lymphomas and stem cell transplant.

Persons living with Multiple Myeloma

Secondary immunodeficiencies have been a major concern in haematological malignancies. We need to remain very careful with the risk of infection.

Dr. Anne Quinquenel (Reims, France)

  • 1. Patel, S. et al., S. Frontiers in Immunology 2019; 10: 33; Tadmor, T. et al, Expert Rev Hematol. 2018; 11 (1): 57-70; Benbrahim, O. et. al., Hematology 2018; 24(1): 173-182; Perez, E. et al., J Allergy Clin Immunol. 2017; 139:S1; Vacca, A. et al., Clinical Immunology 2017; 191: 110-115; EMA, Guideline on core SmPC for human normal immunoglobulin for intravenous administration (IVIg) 2018.
  • 2. Tadmor, T. et al., Expert Review of Hematology 2018; 11:1, 57-70; Hensel, M. et al., Eur J Haematol. 2017; 99(2):169-177; Da Cunha-Bang, C. et al., Blood Cancer J. 2016; 6(11).
  • 3. Perez, E. et al., J Allergy Clin Immunol. 2017; 139:S1; Tomblyn, M. et al., Biol Blood Marrow Transplant. 2009; 15:1143; EMA, Guideline on core SmPC for human normal immunoglobulin for intravenous administration (IVIg) 2018; Debes, A. et al., Pharmacoepidemiol Drug Saf. 2007; 16:1038; Raanani, P. et al., Leuk Lymphoma 2009; 50:764; Benbrahim, O. et al., Hematology 2018; 24(1):173-182.
  • 4. Augustson, B. M. et al., J Clin Oncol. 2005; 23:9219; Teh, B.W., et al., Br J Haematol. 2015; 171: 100-108; Blimark, C. et al., Haematologica 2015; 100 (1) 107-113; Patel, S. et al., Frontiers in Immunology 2019; 10: 33.
  • 5. Ahn, H. et al., Transfusion 2018; 58: 2437-2452; Tomblyn, M. et al., Biol Blood Marrow Transplant. 2009; 15:1143.

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