Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA.

Area of Science:

• Hematology
• Oncology
• Molecular Diagnostics

Background:

• Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) presents heterogeneous outcomes with limited durable remissions using standard therapies.
• Circulating tumor DNA (ctDNA) is a sensitive biomarker with potential prognostic value in R/R DLBCL.

Purpose of the Study:

• To assess baseline ctDNA levels for identifying R/R DLBCL patients at high risk of relapse after polatuzumab vedotin plus bendamustine and rituximab (BR) or BR alone.
• To evaluate ctDNA as a prognostic and monitoring tool in transplant-ineligible R/R DLBCL patients who received at least one prior therapy.

Main Methods:

• A ctDNA assay using a customized panel of recurrently mutated DLBCL genes measured mutant molecules per mL (MMPM) at baseline and end of treatment (EOT).
• Progression-free survival (PFS) and overall survival (OS) were analyzed in subgroups stratified by baseline ctDNA and log-fold change in ctDNA at EOT versus baseline.
• Biomarker-evaluable patients (n=33) had baseline ctDNA correlated with clinical factors like LDH, prior therapies, stage, and IPI.

Main Results:

• High baseline ctDNA (above median MMPM) was independently prognostic for shorter PFS (aHR, 0.18) and OS (aHR, 0.20) after adjusting for key prognostic factors.
• Baseline ctDNA levels correlated with established prognostic markers including LDH, number of prior therapies, stage, and IPI.
• A significantly greater decrease in ctDNA MMPM from baseline to EOT was observed in patients achieving complete response (CR) (n=13) compared to those without CR (n=10) (P=.0025).

Conclusions:

• Baseline ctDNA assessment effectively identifies R/R DLBCL patients at high risk of progression.
• ctDNA shows promise as a tool for monitoring treatment response and guiding management in R/R DLBCL.
• Further evaluation of ctDNA as a monitoring tool in R/R DLBCL is warranted.