Positron-emission tomography (PET)-based metabolic tumor volume could serve as a significant measure of response to chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma, according to the results of a study published in The Journal of Nuclear Medicine. Metabolic tumor volume more accurately predicted progression-free survival outcomes than the standard International Prognostic Index tool.
“This quantitative measurement has the potential to significantly improve pretreatment risk stratification for [patients with] large B-cell lymphoma,” said study lead author Conrad-Amadeus Voltin, MD, Nuclear Medicine Physician at the University Hospital Cologne, Cologne, Germany. “Those with high metabolic tumor burden may benefit from personalized bridging strategies to reduce the tumor volume prior to receiving CAR T-cell therapy.”
Dr. Votlin continued: “Quantitative PET biomarkers such as metabolic tumor volume may further enhance the value of PET for personalized treatment planning, not only in the specific setting of CAR T-cell therapy, but also across other treatment regimens and lymphoma subtypes.”
Background and Study Methods
“CAR T-cell therapy has significantly advanced the treatment of large B-cell lymphoma; however, it's still unclear what baseline parameters and infusion time point are optimal,” said Dr. Votlin. “Quantitative PET biomarkers such as metabolic tumor volume may provide valuable information that can play a central role in personalized treatment planning.”
Researchers sought to identify a biomarker for potential nonresponse among patients with large B-cell lymphoma who are being considered for treatment with CAR T-cell therapy. They considered PET-derived metabolic tumor volume and fluorine F-18–labeled fluorodeoxyglucose–avid lymphoma burden as part of four different risk scores as prognostic markers and compared these with International Prognostic Index performance for predicting patient outcomes.
A total of 111 patients with large B-cell lymphoma were included in the analysis from five German university hospitals and one Italian medical center. The patients all received PET imaging prior to CAR T-cell therapy of tisagenlecleucel or axicabtagene ciloleucel.
Metabolic tumor burden was assessed by a fixed standard uptake value threshold of 4.0 for lesion delineation.
Key Findings
Metabolic tumor volume demonstrated an area under the curve of 0.68 (95% confidence interval [CI] = 0.58–0.78) and a Harrell concordance index (C-index) of 0.59 (95% CI = 0.52–0.66). The researchers found that metabolic tumor burden was a more accurate biomarker than the International Prognostic Index for predicting progression-free survival. The International Prognostic Index's area under the curve was 0.61 (95% CI = 0.49–0.72) and the Harrell C-index was 0.54 (95% CI = 0.47–0.61).
Among all tested risk models, the highest performing model combined metabolic tumor volume and extranodal involvement; however it was not found to be superior to PET-derived tumor volume alone.
“Thus, effective reduction of [metabolic tumor volume] through individualized bridging strategies may play a particularly important role in this specific context,” the study authors concluded.
DISCLOSURES: For full disclosures of the study authors, visit jnm.snmjournals.org.
