As novel agents continue to enter the armamentarium for relapsed/refractory multiple myeloma, it is increasingly important for clinicians to familiarize themselves with their associated adverse events (AEs) that may require supportive care. Optimal supportive care is critical in maximizing clinical benefit with CAR T-cell products and bsAb therapies.

When treating patients who have multiple myeloma with CAR T-cell or bsAb therapy, there is the potential for the development of short- and long-term AEs that need to be addressed with supportive care. During the first few weeks of treatment with these therapies, the most important AEs to watch for are cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).

CRS occurs in most patients who receive CAR T-cell therapy and in a little more than half of patients who receive bsAb therapy. CAR T-cell therapy is associated with a greater incidence of high-grade CRS compared with bsAb therapy, which is very rarely grade 3 or higher. For low-grade CRS, symptom management with antipyretics, intravenous fluids, and supportive measures is typically sufficient, but we are also very comfortable with giving patients an anti–IL-6 receptor therapy such as tocilizumab.

ICANS is common with CAR T-cell therapy use and typically occurs during the first month of treatment, but it is rare with bsAb therapy use and is usually low grade when it does occur. Further, a high disease burden is associated with the development of ICANS during CAR T-cell therapy. Corticosteroids are a key component of ICANS management, and anakinra has also been used. Delayed non-ICANS motor and neurologic toxicities include cranial nerve palsies and parkinsonism, which require a multidisciplinary approach to treatment. Other AEs to be cognizant of during the initial weeks of CAR T-cell therapy are hemophagocytic lymphohistiocytosis and macrophage activation syndrome. These are very rare and can sometimes be the result of disease burden and infection, so you should look for and address any possible underlying causes, in addition to providing supportive therapy.

Infections and hypogammaglobulinemia can occur with the use of both CAR T cells and bsAbs. Although the incidence of infections tends to drop in the months after a patient has received CAR T-cell therapy, the infection risk continues for those receiving bsAbs, as they need treatment regularly. Patients should continue antimicrobial prophylaxis for viruses and Pneumocystis jirovecii pneumonia. In those whose hypogammaglobulinemia persists, intravenous immunoglobulin every 4 to 5 weeks may be required.

An increased incidence of a second primary malignancy has been observed with CAR T-cell therapy, leading to US Food and Drug Administration (FDA) boxed warnings. Some concerns are that the CAR T-cell manufacturing process introduces insertional mutagenesis or that the lymphodepleting chemotherapy causes mutagenesis. T-cell lymphomas related to insertional mutagenesis have been reported very rarely with CAR T-cell therapy. Recently, 2 brief reports published in The New England Journal of Medicine discussed insertional mutagenesis in T-cell lymphomas related to CAR T-cell therapy. It is important to see if this issue can be mitigated by modifying the CAR T-cell manufacturing process.