Dr Hill and colleagues recommended that immunoglobulin (Ig) G replacement should be considered for patients with severe hypogammaglobulinemia (≤ 400 mg/dL) before and after undergoing CAR-T therapy, especially in the context of serious or recurrent bacterial infections. They further suggested that patients should be screened for serum total IgG level before therapy initiation and subsequently at monthly intervals for at least 3 months after completion of CAR-T therapy; patients with IgG level of 400 mg/dL or less and serious, persistent, or recurrent bacterial infections after this timeframe should be treated with IgG supplementation. The review authors noted that patients who experience severe (grade 3 or higher) cytokine release syndrome during treatment may be at higher risk for subsequent infections.
Of note, however, is that there are currently no data to support the benefit of using IgG after CAR-T therapy. Moreover, IgG replacement is expensive, and all IgG products have unique sets of potential side effects that must be considered. Although most adverse effects associated with IgG infusions tend to be transient, infusion-related, and without long-term sequelae, there is a potential for patients to experience more serious effects, and all IgG products sold in the US carry a “black box” warning highlighting concerns about thrombosis, renal dysfunction, and acute renal failure in patients at risk.
As a conservative approach, prophylactic IgG is recommended before the initiation of CAR-T therapy and for 3 months after CAR-T infusion in patients with severe hypogammaglobulinemia; for patients with moderate hypogammaglobulinemia, IgG replacement should be considered if the patient experiences a severe or recurrent infection. Among patients with prolonged B-cell aplasia but normal IgG levels, supplementation could be considered in the context of repeated or severe infections along with evidence of functional humoral immune dysfunction, such as a minimal response to vaccines. For many patients, prophylactic IgG can be safely stopped if preexisting plasma cells persist and some B-cell recovery appears likely.
Thus, to help identify patients who may benefit from IgG replacement, patients should be monitored for infections and laboratory correlates of humoral immune competence, including total IgG, IgM, and IgA. Pathogen-specific antibody levels, B-cell recovery, and responses to vaccines may also aid in the identification of such patients.
“Until more data are available, immunoglobulin replacement should be prioritized in individuals with severe hypogammaglobulinemia, those with recurrent or severe bacterial infections, and young children,” said Dr Hill.
Randomized controlled studies of IgG replacement strategies, immune reconstitution, seroprotection to vaccine-preventable infections, and vaccine responsiveness after CAR-T immunotherapies are crucial in order to improve infection prevention strategies in this rapidly growing patient population.
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Hill JA, Giralt S, Torgerson TR, Lazarus HM. CAR-T — and a side order of IgG, to go? — Immunoglobulin replacement in patients receiving CAR-T cell therapy. Blood Rev. 2019;38:100596.