Imaging-based Toxicity and Response Pattern Assessment Following CAR T-Cell Therapy.

Background Chimeric antigen receptor (CAR) T-cell immunotherapy is increasingly used for refractory lymphoma but may lead to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Imaging may assist in clinical management. Associations between CRS or ICANS grade and imaging findings remain not fully established. Purpose To determine associations between imaging findings and clinical grade of CRS or ICANS, evaluate response patterns, and assess imaging use following CAR T-cell treatment. Materials and Methods Patients with refractory B-cell lymphoma who received CAR T-cell infusion between 2018 and 2020 at a single center were analyzed retrospectively. Clinical CRS or ICANS toxicity grade was assessed using American Society for Transplantation and Cellular Therapy, or ASTCT, consensus grading. Thoracic and head images (radiographs, CT scans, MRI scans) were evaluated. Associations between imaging findings and clinical CRS or ICANS grade were analyzed. Wilcoxon signed-rank and χ2 tests were used to assess associations between thoracic imaging findings, clinical CRS toxicity grade, and imaging-based response. Response to therapy was evaluated according to Deauville five-point scale criteria. Results A total of 38 patients (mean age ± standard deviation, 59 years ± 10; 23 men) who received CAR T-cell infusion were included. Of these, 24 (63% [95% CI: 48, 79]) and 11 (29% [95% CI: 14, 44]) experienced clinical grade 1 or higher CRS and ICANS, respectively. Patients with grade 2 or higher CRS were more likely to have thoracic images with abnormal findings (10 of 14 patients [71%; 95% CI: 47, 96] vs five of 24 patients [21%; 95% CI: 4, 37]; P = .002) and more likely to have imaging evidence of pleural effusions (five of 14 [36%; 95% CI: 10, 62] vs two of 24 [8.3%; 95% CI: 0, 20]; P = .04) and atelectasis (eight of 14 [57%; 95% CI: 30, 84] vs six of 24 [25%; 95% CI: 7, 43]; P = .048). Positive imaging findings were identified in three of seven patients (43%) with grade 2 or higher ICANS who underwent neuroimaging. The best treatment response included 20 of 36 patients (56% [95% CI: 39, 72]) with complete response, seven of 36 (19% [95% CI: 6, 33]) with partial response, one of 36 (2.8% [95% CI: 0, 8]) with stable disease, and eight of 36 (22% [95% CI: 8, 36]) with progressive disease. Conclusion Thoracic imaging findings, including pleural effusions and atelectasis, correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. CAR T-cell therapy yielded high response rates. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Langer in this issue.

Findings on Chest CT Performed in the Emergency Department in Patients Receiving Immune Checkpoint Inhibitor Therapy: Single-Institution 8-Year Experience in 136 Patients.

BACKGROUND. Patients undergoing immune checkpoint inhibitor (ICI) therapy may present to the emergency department (ED) with a wide range of immune-related adverse events. OBJECTIVE. The purpose of our study was to evaluate chest CT findings in patients receiving ICI therapy presenting to the ED and to explore these findings' associations with clinical parameters. METHODS. This retrospective study included 136 patients (75 men, 61 women; mean age, 65 ± 12 [SD] years) receiving ICI therapy who underwent chest CT at 163 ED visits between 2011 and 2018. Two radiologists independently reviewed chest CT examinations for various findings and resolved discrepancies by consensus. Clinical parameters, including survival at last available follow-up, were recorded. Chest CT findings were summarized, and interreader agreement was evaluated using kappa coefficients. Associations between CT findings and clinical parameters were explored using Fisher exact, chi-square, Wilcoxon, and Kruskal-Wallis tests. RESULTS. A total of 62.5% of patients had primary lung cancer; 52.9% received nivolumab monotherapy, and 30.1% received pembrolizumab monotherapy. A total of 55.8% of ED visits occurred within 60 days after ICI initiation. The most common CT findings were worsening lung tumor burden (60.1%), new consolidation unrelated to tumor (30.1%), new or worsening pleural effusion (23.9%), and ICI-associated pneumonitis (12.9%). The most common CT pneumonitis pattern was radiation recall pneumonitis (6/21, 28.6%). A total of 78.5% of ED visits with chest CT resulted in hospitalization; 66.9% of patients subsequently died. Survival was worse for patients with, versus without, worsening tumor (72.2% vs 49.1% of patients deceased vs alive at follow-up, p = .006) and for patients with, versus without, pleural effusion (39.2% vs 17.5% of patients deceased vs alive at follow-up, p = .04). Kappa values for interreader agreement of evaluated chest CT findings ranged from 0.66 (worsening tumor burden) to 1.00 (numerous findings). CONCLUSION. Most ED chest CT examinations in patients receiving ICI therapy exhibited worsening lung tumor burden, which was associated with worse survival. New consolidation and ICI-associated pneumonitis (most commonly radiation recall pneumonitis) were also commonly detected in the ED setting. CLINICAL IMPACT. Understanding pathologies detected on chest CT in patients undergoing ICI therapy who present to the ED may guide radiologists in interpreting such imaging.