ASH 2022: POLARIX Trial Focuses on ctDNA for Risk Profiling in Diffuse Large B-Cell Lymphoma

By: Vanessa A. Carter, BS
Posted: Friday, December 16, 2022

Alex F. Herrera, MD, of the City of Hope Comprehensive Cancer Center, Duarte, California, and colleagues are attempting to validate the prognostic value of circulating tumor DNA (ctDNA) in patients with treatment-naive diffuse large B-cell lymphoma (DLBCL). Presented during the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 542), the results of this prespecified exploratory analysis determined that ctDNA holds prognostic value in this patient population.

“Patients who did not achieve at least a 2.5 log-fold change and/or did not have ctDNA clearance following one cycle of polatuzumab vedotin-piiq, rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] had inferior outcomes than those who did,” concluded the investigators. “Early changes in ctDNA levels may be of use in risk-adapted trial designs to identify patients in need of alternative treatment.”

Patients with previously untreated DLBCL were randomly assigned to receive polatuzumab vedotin plus R-CHP (n = 440) or an R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen (n = 439) regimen. Plasma ctDNA levels were measured at baseline as well as at day 1 of cycle 2.

Results were available for 319 and 299 patients given polatuzumab vedotin plus R-CHP and R-CHOP, respectively. A median of 135 variants were detected in each patient. High baseline mutant molecules per milliliter seemed to correlate with the presence of bulky disease (P < .001). Additionally, those with baseline ctDNA levels above the median mutant molecules had shorter progression-free and overall survival than those with a level below the median.

Stratifying patients in both the polatuzumab vedotin plus R-CHP and R-CHOP cohorts at the log-fold change threshold of at least 2.0 was strongly prognostic of progression-free survival (hazard ratio [HR] = 1.86 vs. 2.21) and overall survival (HR = 1.48 vs. 2.67) outcomes, according to the investigators. Additionally, a log-fold change threshold of 2.5 was better able to identify patients at risk of poorer outcomes, with 24-month progression-free and overall survival rates of 65.7% vs. 87.0% and 86.2% vs. 91.8%, respectively.

Disclosure: For full disclosures of the study authors, visit ash.confex.com.

2022 ASH Annual Meeting and Exposition

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