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Hypogammaglobulinaemia and infection risk after B-cell therapies

aka hypogammaglobulinemia, low immunoglobulins, low IgG, immunoglobulin replacement, IVIG, intravenous immunoglobulin, B-cell depletion, B-cell aplasia, infection risk, opportunistic infections, infection prophylaxis, antimicrobial prophylaxis, antiviral prophylaxis, PJP prophylaxis, Pneumocystis prophylaxis, CMV reactivation, cytomegalovirus, vaccine responses, revaccination

A shortage of antibodies because treatment has wiped out the B cells or plasma cells that make them, as CD19 CAR-T, CD20 antibodies and BCMA therapies deliberately do. It leaves patients prone to infections, sometimes for years, and is managed with immunoglobulin infusions.

Infections are the leading cause of non-relapse death after BCMA and CD19 CAR-T and bispecific antibodies; hypogammaglobulinaemia, prolonged cytopenias, T-cell dysfunction and steroids for CRS all contribute. Management includes IVIG for recurrent infections or IgG <4 g/L, prophylaxis against Pneumocystis, herpes viruses and sometimes fungi, CMV monitoring, and vaccination (non-live; responses are blunted, so household contacts should be vaccinated). Rituximab causes hypogammaglobulinaemia after repeated courses and hepatitis B reactivation. Persistent B-cell aplasia after CD19 CAR-T is also a useful sign that the CAR-T cells remain active.

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