Santiago Thibaud: Multiple Myeloma Risk and Outcomes Associated with PGVs in DNA Repair Genes

Santiago Thibaud shared on X:

“New paper in Blood Cancer Discovery! Thrilled to announce our study: MM Risk and Outcomes Associated with Pathogenic Germline Variants (PGVs) in DNA Repair Genes.

Main findings and key implications.

We analyzed germline whole exomes of 1,681 MM patients from two independent cohorts.

~10% had PGVs in cancer predisposition genes, mostly involved in DNA repair. Important implications for MM patients and families!

PGVs enriched in specific subsets of MM:

• Personal cancer history
• Family cancer history
• Younger age at diagnosis

Should routine germline screening be considered for these MM patients?

BRCA-related pathways were the most affected:

• PGVs in BRCA1/2 or PALB2 were 5x more common in MM vs. healthy controls (OR 4.8; 95% CI 2.8-7.8, FDR <0.0001)
• 63% of BRCA2 PGV carriers showed somatic loss of BRCA2 (del13q) in the tumor

Therapeutic implications: MM patients with high/moderate-penetrance PGVs had significantly longer PFS1 after HDM-ASCT. DNA repair defects enhanced sensitivity to DNA-damaging therapies. Could this guide ASCT eligibility? Role for PARP inhibitors?

Bottom line: Integrating genetic testing into MM care could provide valuable insights for risk assessment and therapeutic strategies. Explore our full findings and stay tuned for more to come!

Grateful for the support from MMRF and The Robert A. Winn Diversity.”

Multiple Myeloma Risk and Outcomes are Associated with Pathogenic Germline Variants in DNA Repair Genes | Blood Cancer Discovery

Authors: Santiago Thibaud, Ryan L. Subaran, Scott Newman, Alessandro Lagana, David T. Melnekoff, Saoirse Bodnar, Meghana Ram, Zachry Soens, William Genthe, Tehilla Brander. Tarek H. Mouhieddine. Oliver Van Oekelen, Jane Houldsworth, Hearn Jay. Cho, Shambavi Richard, Joshua Richter, Cesar Rodriguez, Adriana Rossi, Larysa Sanchez, Ajai Chari, Erin Moshier, Sundar Jagannath, Samir Parekh, Kenan Onel

Source: Santiago Thibaud/X

Santiago Thibaud, MD, is an Assistant Professor of Medicine in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai. In 2021, he received the Young Investigator Award for an abstract at the International Myeloma Workshop and won First Prize for an Oral Presentation at Mount Sinai’s Annual Research Day. Dr. Thibaud specializes in monitoring long-term myeloma patients and managing complications from previous treatments.