In this episode of Blood Cancer Talks, hosts Eddie, Ashwin, and Raj welcome two distinguished experts to explore the cutting-edge field of circulating tumor DNA (ctDNA) in B-cell lymphomas. Dr. David Russler-Germain, a lymphoma clinician from Siteman Cancer Centre at Washington University in St. Louis, returns as a familiar voice to the podcast audience. Joining him is Dr. Ash Alizadeh, the Moghadam Family Professor of Medicine, Oncology, and Hematology at Stanford University and leader of the Cancer Genomics Program at Stanford Cancer Institute. Dr. Alizadeh has been instrumental in advancing our understanding of lymphomagenesis and lymphoma genetics over the past two decades, pioneering multiple ctDNA techniques that are revolutionizing cancer care. Together, they discuss the transformative potential of ctDNA technology in B-cell lymphomas, particularly DLBCL, covering everything from the technical evolution of biomarker detection to groundbreaking clinical data that may reshape how we monitor and treat these aggressive cancers.
Key Discussion Topics
1. Genetic Heterogeneity in B-Cell Lymphomas
Complex genetic landscape of DLBCL
Implications for treatment strategies
Need for personalized approaches
2. Clinical Need for ctDNA in Lymphoma
Why ctDNA is needed in aggressive lymphomas:
Curative vs. non-curative treatment settings
Limitations of current PET imaging
Additional prognostic information beyond imaging
Risk stratification capabilities
Potential to avoid overtreatment
Therapy adaptation opportunities
3. Challenges in Lymphoma MRD Assessment
Why lymphoma MRD is more complex than other hematologic malignancies:
Differences from acute leukemias, CLL, and myeloma
Technical challenges specific to lymphoid tumors
Lower circulating tumor burden compared to liquid tumors
4. ClonoSEQ Technology
Mechanism: Immunoglobulin sequencing approach
Advantages: Established platform with regulatory approval
Disadvantages: Limited sensitivity in peripheral blood, requires adequate tumor sample
5. CAPP-Seq Technology
Full Name: Cancer Personalized Profiling by Deep Sequencing
Innovation: Developed ~10 years ago by Dr. Alizadeh's group
Mechanism: Targeted sequencing of cancer-specific mutations
Advantages: High sensitivity, personalized approach
6. PhasED-Seq Technology
Evolution: Next-generation advancement of CAPP-Seq
Key Improvements: Enhanced sensitivity and specificity
Technical Advances: Phased variant detection
Clinical Data Highlights
1. Remission Assessment by ctDNA in LBCL on 5 prospective studies of frontline anthracycline-based chemo-immunotherapy: https://pubmed.ncbi.nlm.nih.gov/40802906/
2. Prospective validation of end of treatment ctDNA-MRD by PhasED-Seq in DLBCL patients from HOVON-902 clinical trial: https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7000
3. Korean data on prognostic utility of ctDNA: https://ashpublications.org/blood/article/142/Supplement%201/69/501573