Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma

Abstract

We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD(-) by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD(+). When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10(-3) 27 months, MRD 10(-3) to 10(-5) 48 months, and MRD <10(-5) 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD(+). In complete response patients, the TTP remained significantly longer for MRD(-) compared with MRD(+) patients (131 vs 35 months; P = .0009).

© 2014 by The American Society of Hematology.

Figures

Figure 1

TTP and OS of series according to minimal MRD levels. (A) TTP and (B) OS for MRD levels ≤10−5 vs >10−5, as determined by deep sequencing.

Figure 2

TTP and OS of series stratified according to different MRD levels >10−3 vs 10−3 to 10−5 vs <10−5. (A) TTP and (B) OS, as determined by deep sequencing.

Figure 3

Time to progression for patients achieving conventional complete remission (CR), according to minimal residual disease (MRD) status as determined by deep sequencing.