The US Food and Drug Administration approvals of the 2 available CAR T-cell therapies (ie, idecabtagene vicleucel and ciltacabtagene autoleucel) were based on the results of the KarMMa and the CARTITUDE-1 trials, respectively, which enrolled patients with heavily pretreated multiple myeloma (ie, triple-refractory and penta-refractory disease). In these trials, patients achieved impressive response rates with minimal residual disease negativity that occurred very quickly after treatment initiation (ie, often within the first month of treatment). Many patients were able to enter a period of antimyeloma treatment freedom. And, for these patients, this typically comes after years of having to receive multiple agents in combination to control their multiple myeloma, so it can be quite meaningful.

When treating patients with multiple myeloma, it is important to approach them in an open and transparent manner and, in those undergoing CAR T-cell therapy, to accurately describe the process. After the T cells are collected by apheresis, their cells are then processed and expanded into large numbers, which takes, on average, approximately 6 to 8 weeks. During this time (ie, the manufacturing process), patients may require bridging therapy to maintain disease control. Prior to the reinfusion of CAR T cells, patients undergo lymphodepletion therapy (eg, cyclophosphamide and fludarabine), which helps make room for the CAR T cells to be transfused and expand within the patient. 

Once the CAR T cells have been infused, the 2 major adverse events that patients should be aware of and monitored for are cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). CRS reflects the ongoing immune reaction between the patient’s effector T cells, CAR T cells, and multiple myeloma cells. It is characterized by fever, rigors, tachycardia, and, potentially in severe cases, hypotension, tachypnea, hypoxemia, and other signs of systemic inflammation. There is a standard system for grading the severity of CRS, and there are guidelines to help with management. If a patient's CRS is sufficiently severe, tocilizumab, which targets interleukin 6, and/or corticosteroids can be used to successfully control the reaction in most cases. The severity of that adverse effect, which was noted in the earliest clinical trials, can now be mitigated very effectively with tocilizumab and/or steroids.

ICANS is a neurologic side effect that can occur after a patient with multiple myeloma receives CAR T-cell therapy, and it is most commonly observed in those with a large tumor burden. Features include aphasia, altered consciousness, cognitive skill impairment, weakness, seizures, and cerebral edema. Reducing the patient's tumor burden prior to CAR T-cell infusion, as well as early recognition, have been successful in mitigating the severity of ICANS. 

In addition to CRS and ICANS, another more long-term consequence of CAR T-cell therapy is the development of immune suppression. This occurs in some patients because normal antibody-forming immune cells can be depleted, since these cells carry the same antigens that are targeted on the malignant cells. Patients should be monitored carefully for infection, and intravenous immunoglobulin replacement therapy should be administered, if indicated. 

Overall, I think that patients should be reassured that CAR T-cell therapy is an exciting new modality that achieves an unprecedented frequency and extent of response, including minimal residual disease negativity, that can allow them to be off further treatments—often for the first time in many years. Importantly, it also requires that they be monitored carefully for toxicities and be protected against infection because their humoral immunity is also compromised.