Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients

Sridurga Mithraprabhu, Rachel Morley, Tiffany Khong, Anna Kalff, Krystal Bergin, Jay Hocking, Ioanna Savvidou, Kathryn M. Bowen, Malarmathy Ramachandran, Kawa Choi, Boris Ka Leong Wong, John Reynolds, Andrew Spencer

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Monitoring tumour burden and therapeutic response through analyses of circulating cell-free tumour DNA (ctDNA) and extracellular RNA (exRNA) in multiple myeloma (MM) patients were performed in a Phase Ib trial of 24 relapsed/refractory patients receiving oral azacitidine in combination with lenalidomide and dexamethasone. Mutational characterisation of paired BM and PL samples at study entry identified that patients with a higher number of mutations or a higher mutational fractional abundance in PL had significantly shorter overall survival (OS) (p = 0.005 and p = 0.018, respectively). A decrease in ctDNA levels at day 5 of cycle 1 of treatment (C1D5) correlated with superior progression-free survival (PFS) (p = 0.017). Evaluation of exRNA transcripts of candidate biomarkers indicated that high CRBN levels coupled with low levels of SPARC at baseline were associated with shorter OS (p = 0.000003). IKZF1 fold-change <0.05 at C1D5 was associated with shorter PFS (p = 0.0051) and OS (p = 0.0001). Furthermore, patients with high baseline CRBN coupled with low fold-change at C1D5 were at the highest risk of progression (p = 0.0001). In conclusion, this exploratory analysis has provided the first demonstration in MM of ctDNA for predicting disease outcome and of the utility of exRNA as a biomarker of therapeutic response.

Original languageEnglish
Pages (from-to)2022-2033
Number of pages12
JournalLeukemia
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 2019

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