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 burden of infection in Chronic Lymphocytic Leukaemia and Multiple Myeloma

Tadeusz Robak, Medical University of Lodz, Poland

Haematological malignancies such as Chronic Lymphocytic Leukaemia (CLL) or Multiple Myeloma (MM), and their treatment are common causes of secondary immunodeficiency (SID, hypogammaglobulinaemia). SID is often multifactorial in aetiology, related to both the underlying condition and its treatment, including a growing range of treatments targeting B-cells.

As the EHA25 virtual congress took place during the Covid-19 pandemic, a focus was also made on patients with Covid-19 and CLL or MM.

Prof. Tadeusz Robak Presentation at the EHA25 virtual congress

Infection complications of CAR T (chimeric antigen receptor-modified T-cell) immunotherapy

Marion Subklewe, Ludwig Maximilian University, Munich, German

The development and regulatory approval of chimeric antigen receptor T cell (CAR T) therapies targeting the B lineage surface antigen CD19 represents a major milestone in cancer immunotherapy. This therapy also results in depletion of normal CD19+ B cells and is associated with hypogammaglobulinaemia. This may result in an increased risk for infection.

Because the CAR T-cells can proliferate and survive in vivo, this B-cell aplasia and gaps in humoral immunity may continue as a long-term problem.

Prof. Marion Subklewe Presentation at the EHA25 virtual congress

Recommendations and consensus for the use of IgG therapy in patients with haematological malignancies and secondary immunodeficiency

Michael Albert, Ludwig Maximilian University, Munich, Germany

Optimizing SID treatment requires careful clinical and laboratory assessment and may involve close monitoring of risk parameters, vaccination, antibiotic strategies, and in some patients, immunoglobulin replacement therapy (IgRT). New guidelines for the use of human normal immune globulins in SID patients were implemented by the European Medicines Agency (EMA) in 2019. Despite these new guidelines, significant variation remains across European countries in the assessment and approaches to reducing the burden of infections.

A European Delphi consensus exercise was initiated to develop recommendations on how to diagnose, treat and follow-up patients with antibody deficiency associated with haematological malignancies, based on experiences and practice from haemato oncologists and immunologists. Analysis of the full results in six areas (Definition of infections, Measuring IgG levels, Initiating IgRT, IgRT dosing, SCIg usage and Discontinuing IgRT) identified by a Task Force and evaluated by a panel of 32 European experts were presented to offer recommendations and help guide the management of SID in patients with haematological malignancies.

Prof. Michael Albert Presentation at the EHA25 virtual congress

Future perspectives and closing remarks

Tadeusz Robak, Medical University of Lodz, Poland

Data from a recent survey about physicians’ practice in haematological malignancies associated with SID showed that serum immunoglobulin are measured in 83% of MM patients, 76% of CLL patients and 69% of NHL patients. It also showed that 85% of the physicians prescribe IgRT after two or more severe infections.

Immunoglobulin therapy is efficacious in immune compromised patients with haematological malignancies. It is very well tolerated and can reduce the infection risk and infection frequency. IgRT can be administered intravenously or subcutaneously.

More data to demonstrate the role of IgRT as primary infection prophylaxis in CLL patients with secondary immunodeficiency are needed. A new phase III clinical trial will try to answer this question.

Prof. Tadeusz Robak Presentation at the EHA25 virtual congress

More information about secondary immunodeficiency in chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia

More information about Immunoglobulin therapy for secondary immmunodeficiencies associated with haematological malignancies

Immunoglobulin therapy