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AACR 2022: Circulating Tumor DNA Mutations and Relapse in Refractory Myeloma

By: Sarah Campen, PharmD
Posted: Wednesday, April 20, 2022

Circulating tumor DNA (ctDNA) mutations appear to be prognostic biomarkers of outcome to secondary salvage therapy in high-risk patients with multiple myeloma and may enable the design of targeted therapeutic approaches, according to a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 3373/1). Sridurga Mithraprabhu, PhD, of Monash University, Melbourne, Australia, and colleagues employed an ultrasensitive targeted amplicon sequencing assay to identify the somatic variants that correlated with shorter progression-free and overall survival: RAS/RAF and ATM/ATR/TP53 mutations.

This phase II, single-arm study included 50 newly diagnosed transplant-eligible patients with multiple myeloma that was refractory to or demonstrated a suboptimal response to bortezomib-based induction therapy. All participants were treated with a regimen of carfilzomib, thalidomide, and dexamethasone; peripheral blood plasma and bone marrow samples were obtained at baseline, in cycle 3 on day 1, and at the end of study or at relapse.

Targeted amplicon sequencing was performed on 31 bone marrow samples and 48 samples of ctDNA. In bone marrow, KRAS mutations were detected in 42% of patients and ATR mutations in 29%. In ctDNA, ATR mutations were most common (36%), followed by FGFR3 (27%) and ATM (26.8%).

The presence of ctDNA mutations at baseline for patients who did not relapse versus those who did relapse on the carfilzomib, thalidomide, and dexamethasone regimen was significantly different: 3% versus 25% (RAS/RAF) and 17% versus 41% (ATM/ATR/TP53), respectively (P < .0001). Patients with these ctDNA mutations at baseline had significantly shorter progression-free (P = .003) and overall survival (P = .02).

Disclosure: For full disclosures of the study authors, visit

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