Biomarker-adapted treatment in high-risk large B-cell lymphoma

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• High-risk large B-cell lymphoma (LBCL) presents inadequate survival rates, especially with specific biological risk factors.
• Current treatment strategies require refinement to improve outcomes for these patients.

Purpose of the Study:

• To evaluate a biomarker-driven phase II trial for high-risk LBCL patients.
• To assess the efficacy of R-CHOEP-14 and DA-EPOCH-R regimens based on biological risk profiles.
• To investigate the prognostic value of circulating tumor DNA (ctDNA) kinetics and genetic aberrations.

Main Methods:

• A phase II trial enrolled 123 high-risk LBCL patients (aged 18-64).
• Patients received R-CHOEP-14 or DA-EPOCH-R based on biological risk factors (e.g., C-MYC translocation, TP53 deletion, MYC/BCL2 co-expression).
• Circulating tumor DNA (ctDNA) levels and kinetics were monitored during therapy.

Main Results:

• Three-year failure-free survival (FFS) and overall survival (OS) were 79% and 88% for the entire cohort.
• DA-EPOCH-R did not show improved survival compared to R-CHOEP-14 in high-risk patients.
• High pretreatment ctDNA, TP53 deletion/mutations, and end-of-therapy (EOT) ctDNA positivity correlated with worse outcomes.
• EOT ctDNA negativity indicated a cure and resolved false positive PET scans.

Conclusions:

• Biomarker-guided therapy shows promising survival for high-risk LBCL patients.
• TP53 aberrations and high ctDNA levels (pretreatment or EOT) predict poor prognosis.
• ctDNA kinetics serve as a valuable tool for monitoring treatment response and predicting outcomes.