Abstract 5710: Detection and monitoring of t(11;14) in liquid biopsies from patients with relapsed/refractory multiple myeloma treated with venetoclax-based regimens

Abstract. Venetoclax (Ven) is a selective B-cell lymphoma 2 inhibitor being studied in t(11;14)+ relapsed/refractory multiple myeloma (MM) Detection of t(11;14) in MM requires bone marrow (BM) aspiration and evaluation of CD138+ plasma cells by fluorescence in situ hybridization (FISH) Innovative techniques may provide less invasive detection of t(11;14) in liquid biopsies Here we present results of the SAGAsign® integrated approach combining low-coverage whole-genome sequencing (WGS) to characterize t(11;14) breakpoints together with personalized digital polymerase chain reaction (dPCR) assays to efficiently detect and monitor the genomic rearrangements in circulating tumor DNA (ctDNA) Baseline BM aspirates were collected from 270 patients (pts) from Ven clinical trials (NCT02755597, NCT01794520, NCT03314181, NCT02899052) Previously generated WGS to an average coverage ~22 × was used Paired samples of peripheral blood mononuclear cell (PBMC) DNA and plasma circulating cell-free DNA (cfDNA) were analyzed by dPCR at timepoints after Ven-based treatment Of the 90 t(11;14)+ pts by FISH, 160 t(11;14) breakpoints were identified by WGS in 74 pts (concordance in Table) At the time of data cutoff, dPCR assays were designed and evaluated in 8 t(11;14)+ pts; 7/8 (88%) and 6/8 (75%) pts had detectable t(11;14) in cfDNA or PBMCs, respectively Higher levels of t(11;14) mutant allele frequency (MAF) were observed in cfDNA compared with PBMCs After Ven-based treatment, t(11;14) MAF in cfDNA became undetectable in pts with a complete response In conclusion, this approach has the capability to reconstruct t(11;14) breakpoints from WGS data that is highly concordant with FISH; translocations appear more readily detectable in cfDNA than PBMC samples from pts with MM SAGAsign assays detected and monitored t(11;14) in liquid biopsies thus highlighting its potential utility for identifying pts with t(11;14) for targeted therapiesConcordance between WGS and FISH testing for t(11;14)Samples, nFISH+FISH−TotalWGS+741183WGS−16169187Total90180270Concordance, %n/N95% CIt(11;14) positive82.274/9072.7-89.5t(11;14) negative93.9169/18089.3-96.9Overall testing90.0243/27085.8-93.3Citation Format: Xiaotong Li, Lao H. Saal, Christian Brueffer, Yilun Chen, Johanna Asklin, Saman Alvi, Srinivas Venkatram, Jeremy A. Ross. Detection and monitoring of t(11;14) in liquid biopsies from patients with relapsed/refractory multiple myeloma treated with venetoclax-based regimens. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5710.