Circulating Tumour DNA Measurements As an Early Prognostic Indicator for Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with Pola-R-CHP Regimen

Objective

The POLARIX trial showed that pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) significantly improved 2-year event-free survival (EFS) and progression-free survival (PFS) compared with R-CHOP in DLBCL patients with intermediate- and high-risk. However, some patients still failed to achieve durable remission. Circulating tumour DNA (ctDNA) is a novel prognostic biomarker in diffuse large B-cell lymphoma, but its prognostic significance in DLBCL patients treated with pola-R-CHP has not been fully defined. This prospective multicentre study preliminarily evaluated the correlation between baseline ctDNA levels and early post-treatment ctDNA changes with efficacy in Chinese DLBCL patients receiving the pola-R-CHP regimen (ChiCTR2300077262).

Methods

Enrolled DLBCL patients were treated with the pola-R-CHP regimen. Patients' ctDNA samples were subjected to targeted next-generation sequencing (NGS) to analyse the mutational profiles of 168 gene panels. ctDNA testing was performed prior to treatment, on day 1 of cycle 2 (C2D1) and on day 1 of cycle 5 (C5D1), respectively, and imaging efficacy was assessed every 2 cycles.

Results

A total of 22 patients were enrolled between November 2023 and May 2024, of whom 21 (95.5%) had ctDNA mutations detected at baseline. The most frequently mutated genes were PIM1 (42%), TP53 (26%), TMSB4X (26%), BTG2 (26%) and TET2 (21%). Baseline ctDNA levels correlated with IPI but not with age, gender, lactate dehydrogenase(LDH), pathological subtype, stage, Bone marrow infiltration or not, and large masses. Patients in the IPI 4-5 group had significantly higher baseline ctDNA levels than those in the IPI 0-3 group (P = 0.0015). ctDNA was performed at C2D1 in 16 patients and all patients had a significantly lower ctDNA level, with the 8 patients with undetectable ctDNA in durable remission, while 1 of the 8 patients with detectable ctDNA had disease progression. In this case, the patient's ctDNA was found to be elevated from previous levels at C5D1, and was subsequently assessed as disease progression by imaging after 6 cycles, with the ctDNA elevation occurring earlier than the imaging assessment. With a median follow-up of 7.7 months (2.5-16.2), patients with ctDNA >1000 hGE/ml had better PFS than patients with ctDNA ≤ 1000 hGE/ml, but no statistical significance was seen between the two groups (P=0.0612), possibly due to the small sample size and shorter follow-up.

Conclusions

Sustained remission status in DLBCL patients receiving pola-R-CHP may be associated with early clearance of ctDNA, and non-invasive ctDNA assessment may allow risk stratification and outcome prediction in this group of patients. We will subsequently continue to enroll more patients with extended follow-up to further clarify the long-term prognostic significance of ctDNA.

No relevant conflicts of interest to declare.