Immunoglobulin Replacement Therapy (IgRT) for the Treatment of Haematological Malignancy Associated Secondary Immunodeficiency (HM-SID) – a Large UK Tertiary Centre Experience

Haematological malignancy (HM) associated secondary immunodeficiency (HM-SID) is characterised by recurrent infections in the context of hypogammaglobulinaemia. It can be driven by the underlying malignancy or its treatments such as with chemotherapy and immunotherapy. HM-SID is often treated with immunoglobulin replacement therapy (IgRT).

Here, we present a cross-sectional analysis of all patients receiving IgRT for HM-SID at our haemato-oncology centre between January 2022 – December 2023. One hundred and ten patients were identified using pharmacy records. Data collection was performed by independent clinical review of patient records by at least two clinicians.

The median age at commencement of IgRT was 63 years (range 15-85); 42 (38%) were female. Underlying HM included plasma cell dyscrasia (30, 27%), chronic lymphocytic leukaemia, CLL (10, 9%), aggressive B-cell non-Hodgkin’s lymphoma (NHL) (27, 25%), indolent B-cell NHL (26, 24%), Hodgkin’s lymphoma (2, 2%), T-cell lymphoma (1, 1%), acute myeloid leukaemia (3, 3%), B acute lymphoblastic leukaemia (13, 12%) and other myeloid disorders (4, 4%). Five patients had >1 HM (CLL/NHL and myeloid).

Median number of lines of systemic anti-cancer therapy (SACT) was 4 (range 1-12); 66% had already received >2 lines. Sixty-three (57%) had received anti-CD20 directed therapy, 11 (10%) anti-CD52, 2 (2%) anti-thymocyte globulin, 22 (20%) allogeneic stem cell transplant, 46 (42%) autologous stem cell transplant, 34 (31%)

Seventy-six (69%) commenced IgRT after January 2021; of these, 32 (42%) had previously received CART and 30 (39%) had previously received TCE. Thirty-four (31%) commenced IgRT prior to January 2021; 2 (6%) previously received CART and none previously received TCE.

The majority of IgRT (91%) was administered in the outpatient setting. Median frequency of administration was 4-weekly (range 1-8), median weight-based dose was 0.4 g/kg (range 0.4-2.0) and total dose was 30g (15-180).

In the 6 months prior to IgRT commencement, the median number of bacterial infections requiring either antibiotic therapy or hospitalisation was 2 (range 0-9; 93 [85%] patients experienced at least 1 infection), median serum IgG was 2.1 g/L (range 0-10.0; 88 [80%] patients <4 g/L) and 36 (33%) received continuous prophylactic antibiotic therapy. In the 6 months following IgRT commencement, the median number of bacterial infections requiring either antibiotic therapy or hospitalisation was 0 (range 0-5; 59 [54%] did not experience infection), median serum IgG was 4.1 g/L (range 0.1-12.0; 43 [39%] patients <4 g/L) and 75 (68%) experienced a reduction in infection rate.

The median duration of IgRT was 13 months (range 1-244; 76 [69%] received >6 months). Forty-five (41%) experienced an adverse event (AE) due to IgRT (44 allergy/infusion reaction [grade 1], 1). There were no treatment discontinuations due to AEs. Twenty-six (24%) discontinued treatment, due to change in clinical status (20), patient preference (4) and other (2).

Our experience suggests that IgRT is an effective treatment for HM-SID, with most patients deriving a reduction in infection rate in the 6 months following treatment. IgRT also appears to be well tolerated, with no treatment discontinuations due to AEs.

The treatment landscape for HM has evolved over the last decade with the advent of immunotherapies such as CART and TCE, which may predispose patients to HM-SID as a result of B-cell aplasia (case series have reported IgRT in up to 36.6% of CART patients). A large proportion of patients at our centre treated since January 2021 had a history of prior treatment with CART or TCE, suggesting an emergent patient population at risk of HM-SID requiring treatment.

Randomised control trial data is needed to accurately quantify the benefit of IgRT in the reduction of bacterial infection burden and the effect on patient reported outcomes, particularly in the context of those treated with immunotherapy.