Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry

• Published in: Leukemia Vol. 28; no. 2; pp. 391 - 397
• Main Authors: Puig, N, Sarasquete, M E, Balanzategui, A, Martínez, J, Paiva, B, García, H, Fumero, S, Jiménez, C, Alcoceba, M, Chillón, M C, Sebastián, E, Marín, L, Montalbán, M A, Mateos, M V, Oriol, A, Palomera, L, de la Rubia, J, Vidriales, M B, Bladé, J, Lahuerta, J J, González, M, Miguel, J F S, García-Sanz, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2014; Nature Publishing Group
• Subjects: 631/1647/1407/1492; 631/1647/1513/2216; 692/699/67/1990/804; 692/700/139; Alleles; Allelomorphism; Bone marrow; Cancer Research; Care and treatment; Clinical trials; Comparative analysis; Critical Care Medicine; Diagnosis; Flow Cytometry; Gene Rearrangement, B-Lymphocyte; Genetic aspects; Hematology; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin kappa-Chains - genetics; Intensive; Internal Medicine; Leukemia; Medical prognosis; Medicine; Medicine & Public Health; Minimal residual disease; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Neoplasm, Residual - diagnosis; Neoplasm, Residual - genetics; Oligonucleotides; Oncology; original-article; Patients; Quantitation; Real-Time Polymerase Chain Reaction; Risk groups; Sequence Analysis, DNA; Survival; Transplants & implants; Tumor cells; Spain; multiparameter flow cytometry; multiple myeloma; minimal residual disease; ASO RQ-PCR
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2013.217

We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (MM), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection ( n =31), unsuccessful sequencing ( n =17) and suboptimal ASO performance ( n =51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted ( r =0.881, P <0.001), being reflective of treatment intensity. Patients with <10 −4 residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P =0.002), with similar results observed with MFC. Among complete responders ( n =62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P =0.001) and overall survival (NR vs 60 months, P =0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in MM.