Clinical labs have an important role in managing patients who undergo adoptive cellular immunotherapy using T-cells genetically modified with chimeric antigen receptors (CAR T-cells). A review by Suzanne R. Thibodeaux, MD, PhD and Michael C. Milone, MD, PhD in April’s Clinical Chemistry discusses the landscape of this novel therapy, how it differs from more traditional treatments, its potential side effects, and how lab testing supports this therapy.

“We have entered a new era of cancer therapy, with a number of immune-based therapies already used clinically as a standard of care,” wrote Thibodeaux and Milone. “CAR T-cells have produced clinical responses in B-cell malignancies that are otherwise refractory to conventional therapies.” In 2017, the Food and Drug Administration approved two CAR T-cell therapies, tisagenlecleucel and axicabtagene ciloleucel, to treat relapsed and refractory B-cell malignancies in the United States.

Other CAR T-cell therapies are being developed for clinical use, noted the authors.

But CAR T-cell therapy can produce complications, sometimes life-threatening ones. The most common sequela is cytokine release syndrome (CRS), which usually manifests in early stages as a fever, but often presents as a number of symptoms about 4 to 10 days after infusion, when CAR T-cell concentrations peak in blood. Many CRS patients develop severe conditions such as hypotension, hypoxia, and end organ damage, and may require oxygen therapy, mechanical ventilation or vasopressors. Grading systems can assess the severity of and help guide therapy for this serious side effect of CAR T-cell therapy, yet, prospective studies are needed to identify robust biomarkers for CRS, the authors stressed.

Neurotoxicity can also take place with CAR T-cell infusion, marked by symptoms of confusion and delirium, encephalopathy, obtundation, and seizure. “Although most cases occur in the absence of detectable pathology by imaging, cerebral edema and hemorrhage have been observed, particularly in severe cases, and imaging abnormalities portend a poor prognosis,” wrote Thibodeaux and Milone. The therapy has also been linked with other types of toxicity and allergic reactions such as anaphylaxis.

Through routine clinical chemistry testing, labs can assess whether organ damage and dysfunction took place either during or after CRS. The challenge, is to distinguish this condition from other types of systemic inflammation. “This differentiation is especially problematic in the setting of neutropenia, which is frequently present owing to the lymphodepleting chemotherapy given before CAR T-cell infusion in most patients,” wrote the review authors.

Due to its role in monitoring for disease relapse, flow cytometry labs also play an integral role in managing patients treated with CAR T-cells, continued Thibodeaux and Milone. “In B-acute lymphoblastic leukemia, “CD19 antigen or epitope loss on the malignant cells is the most common mechanism of relapse, accounting for as much as two-thirds of cases. Therefore, CD19 should not be used as a sole marker for B-cell identification in the setting of CAR T-cells,” they advised.

Serologic testing for antibodies can help diagnose diseases such as hepatitis and HIV, as well as blood compatibility testing. However, CAR T-cell therapy targeting B cells can affect its results. Although clinical trials have used quantitative polymerase chain reaction to monitor CAR T-cell engraftment and persistence, developers have yet to produce a clinical assay that uses molecular detection to identify CAR T-cells.

Pick up April’s Clinical Chemistry to learn more about clinical labs’ role in managing patients treated with CAR T-cell therapy.