Using Imaging to Identify CAR T-cell Therapy Toxicities

In patients with refractory B-cell lymphoma, thoracic imaging findings correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. This is according to a study published in Radiology which also showed that CAR T-cell therapy yielded high rates of imaging-based treatment response.

“Imaging plays a critical role in the evaluation of clinical cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS) toxicity following CAR T-cell treatment,” wrote Daniel Smith, M.D., a radiologist at the University Hospitals Cleveland Medical Center in Ohio. “Specific findings at thoracic imaging—in particular, pleural effusion and atelectasis—may prove useful correlates for severe clinical grades of cytokine release syndrome, while findings related to ICANS tend to be less specific and less frequent. “

CAR T-cell immunotherapy is increasingly used for refractory lymphoma, but it may lead to cytokine release syndrome and ICANS in the early period following infusion. The associations between cytokine release syndrome or ICANS grade and imaging findings are not established. The goal of this study was to characterize thoracic and neuroimaging findings associated with cytokine release syndrome and ICANS in patients with refractory B-cell lymphoma.

The retrospective analysis included 38 patients (mean age 59; 61% men) with refractory B-cell lymphoma who underwent CAR T-cell infusion. Of these, 63% and 29% experienced clinical grade 1 or higher cytokine release syndrome and ICANS, respectively. Patients with grade 2 or higher cytokine release syndrome were more likely to have thoracic imaging evidence — at radiography, CT and/or MRI — of pleural effusions (36% vs 8.3%, P = .04) and atelectasis (57% vs 25%, P = .048) than patients without cytokine release syndrome or with grade 1 toxicity. Positive imaging findings were identified in 43% with grade 2 or higher ICANS who underwent neuroimaging. Patients undergoing CAR T-cell therapy had higher rates of clinical response, including 56% with complete response and 19%with partial response.

“Our findings further highlight the central role of PET/CT in disease response after CAR-T cell therapy,” the authors wrote.

Limitations of the study included its retrospective design, small sample size, and that most patients without toxicity did not undergo imaging.

In an accompanying editorial, Mark Langer, M.D., professor of clinical radiation oncology at Indiana University School of Medicine, wrote that “in the study by Smith et al, atelectasis and pleural effusions were more common in patients with severe cytokine release syndrome than in those with mild or absent cases. Edema and airway consolidation were not more common.” He added, “Whether such features emerge only when the case becomes clinically more severe or whether these features are early signs of disease that will eventually evolve into a higher-grade condition is a question deserving of future study.

“As more data are prospectively obtained, imaging guidelines to better monitor for the important conditions examined here may be established, and the information collected used to effectively intervene early in detection and treatment,” Dr. Langer wrote.