A key concern has been cytokine release syndrome (CRS), known to commonly cause fever and organ dysfunction from CAR T and less often from other types of immunosuppressants. This was reported in 56% of patients, although it may sometimes be difficult to distinguish from actual disease flares.1
Scientists anticipated that the impact of CRS might be less severe in SLE patients receiving CAR T compared to those receiving it for malignancies, due to the greater numbers of cells targeted in the latter. Consistent with this, Dr. Merrill noted that 98% of these cases in CAR T for SLE have been either grade one or grade two, transient but manageable with therapies such as tocilizumab.1 “Most lupus patients have experienced worse symptoms when they flare,” she said.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a poorly understood side effect of CAR T and sometimes other immunosuppressives that might occur with or without CRS. Dr. Merrill shared that these symptoms, reported in 3% of patients, all resolved with steroid treatment, and only one was a grade four event.1
Some patients had cytopenias, although generally not as severe as those in the hematology literature, Dr. Merrill noted. Relatedly, about 8% of patients developed a serious infection, with one case of fatal pneumococcal meningitis.1 From Dr. Merrill’s perspective, these numbers are not especially high given rates in previous SLE trials, especially given that patients chosen to receive CAR T may be an especially sick population.
Dr. Merrill also discussed a recently described side effect of CAR T therapies in patients with autoimmune diseases: local immune effector cell-associated toxicity syndrome (LICATS). LICATS symptoms are mild and transient symptoms occurring after CAR T therapy which mirror those from the original disease (e.g., lupus-type symptoms for an SLE patient versus those of a patient with systemic sclerosis).2,3
Although the authors made several arguments that these symptoms constitute true CAR T side effects and not just mild symptom flares, Dr. Merrill argued that it’s impossible to completely know this now.3 How scientists define these symptoms—as flares vs. adverse events—may impact how study results are reported and interpreted.
Lack of True Comparators & Needed Research
Dr. Merrill also emphasized the need for true comparators to fully understand the results of these studies. “I think there is a fundamental kind of skepticism that we need to maintain when we look at data from trials that are not controlled with placebo,” said Dr. Merrill, “because we’re not 100% sure of what we’re looking at.”
