Assessment of molecular remission rate after bortezomib plus dexamethasone induction treatment and autologous stem cell transplantation in newly diagnosed multiple myeloma patients

Silvennoinen, Raija; Kairisto, Veli; Pelliniemi, Tarja‐Terttu; Putkonen, Matti; Anttila, Pekka; Säily, Marjaana; Sikiö, Anu; Opas, Jorma; Karri, Penttilä; Kuittinen, Taru; Honkanen, Tuomo; Lundán, Tuija; Juvonen, Vesa; Luukkaala, Tiina; Remes, Kari

doi:10.1111/bjh.12139

Cited by 15 publications

(21 citation statements)

References 8 publications

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“…6 Nonetheless, a clone-specific primer is mandatory for PCR assays, and the success rate in designing such clone-specific and sensitive assays has varied from 42 to 100%. 6, 7,11,13,20 …”

Section: Discussionmentioning

confidence: 99%

“…By sequencing all these rearrangements and using alternate locations for consensus primers and, if necessary, even individualized TaqMan probes to cover cases with somatic mutations in the V-gene, it should be possible to attain a much higher feasibility rate. We have taken three steps to enhance the feasibility of ASO RQ-PCR 11 in our patient cohort of consecutive and unselected symptomatic MM patients in nCR/CR, namely (1) use of singleplex Ig consensus primers in addition to the multiplex primer approach, (2) inclusion of the light chain rearrangements for clonality detection and (3) if necessary, use of a reverse-oriented allele-specific primer and individually designed TaqMan probe in the ASO RQ-PCR analysis.…”

Section: Discussionmentioning

confidence: 99%

“…11 In the present study, we compared MFC with ASO RQ-PCR in all the 129 paired follow-up samples currently available from these patients for MRD evaluation. In addition, the response assessment by MFC and ASO RQ-PCR is compared with immunofixation electrophoresis (IFE) and free light chain (FLC) ratio.…”

Section: Introductionmentioning

confidence: 99%

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Comparative analysis of minimal residual disease detection by multiparameter flow cytometry and enhanced ASO RQ-PCR in multiple myeloma

Silvennoinen

Lundán

Kairisto

et al. 2014

Blood Cancer Journal

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Multiparameter flow cytometry (MFC) and allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) are the two most sensitive methods to detect minimal residual disease (MRD) in multiple myeloma (MM). We compared these methods in 129 paired post-therapy samples from 22 unselected, consecutive MM patients in complete/near complete remission. Appropriate immunophenotypic and ASO RQ-PCR-MRD targets could be detected and MRD analyses constructed for all patients. The high PCR coverage could be achieved by gradual widening of the primer sets used for clonality detection. In addition, for 13 (55%) of the patients, reverse orientation of the ASO primer and individual design of the TaqMan probe improved the sensitivity and specificity of ASO RQ-PCR analysis. A significant nonlinear correlation prevailed between MFC-MRD and PCR-MRD when both were positive. Discordance between the methods was found in 32 (35%) paired samples, which were negative by MFC-MRD, but positive by ASO RQ-PCR. The findings suggest that with the described technique, ASO RQ-PCR can be constructed for all patients with MM. ASO RQ-PCR is slightly more sensitive in MRD detection than 6−10-color flow cytometry. Owing to technical demands ASO RQ-PCR could be reserved for patients in immunophenotypic remission, especially in efficacy comparisons between different drugs and treatment modalities.

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“…6 Nonetheless, a clone-specific primer is mandatory for PCR assays, and the success rate in designing such clone-specific and sensitive assays has varied from 42 to 100%. 6, 7,11,13,20 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparative analysis of minimal residual disease detection by multiparameter flow cytometry and enhanced ASO RQ-PCR in multiple myeloma

Silvennoinen

Lundán

Kairisto

et al. 2014

Blood Cancer Journal

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“…The study shows that MRD negativity is associated with a longer progression-free survival (HR=0.35; P<0.001) and overall survival (HR=0.48; P<0.001) (20), supportive of MRD becoming a regulatory endpoint for drug approval in newly diagnosed multiple myeloma (Figure 1). Because there has not been any defined criteria for the definition of MRD negativity, until date (6); among the four studies included in the main analysis (15, 21-23), three used multiparameter flow-cytometry (15, 21, 22) and one study used allele-specific quantitative polymerase chain reaction (23), both with a sensitivity of at least 1 in 10,000 cells (10 -4 ) to determine MRD status (17). The past few years, several assay platforms have been launched to determine MRD status in multiple myeloma patients.…”

Section: Assessment Of Responsementioning

confidence: 99%

“…Note: Four studies with information on MRD status and hazards ratios for progression-free survival were included in the final analysis (15, 21-23); three studies had information on overall survival (15, 21, 22) (however, one study had no deaths during the original follow-up window (15)) so two studies provided hazards ratios for overall survival. Reprinted from ref.…”

Section: Figurementioning

confidence: 99%

New Developments in Diagnosis, Prognosis, and Assessment of Response in Multiple Myeloma

Landgren

Rajkumar

2016

Clinical Cancer Research

108

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The past few years, the management of multiple myeloma has changed. We have new guidelines regarding how to set the diagnosis, when to initiate therapy, and how to monitor treatment response. In 2014, the updated IMWG diagnostic criteria changed the definition of multiple myeloma; from being a disease defined by symptoms to a disease defined by biomarkers. Today, modern combination therapies have reported up to 60-80% of patients reaching a complete response. As a logical and necessary step forward, investigators have explored strategies to detect minimal residual disease (MRD) and its correlation with clinical outcomes. Recent meta-analysis data show that MRD negativity is associated with longer progression-free survival and overall survival. In 2016, the updated IMWG response criteria include MRD as the deepest level of treatment response in multiple myeloma. Simultaneously, we are still quite behind in our understanding of the heterogeneous biology of multiple myeloma and its implications to therapy. Emerging DNA sequencing data show that newly diagnosed multiple myeloma patients have a broad range of mutations which are distributed unevenly in multiple parallel sub-clones present already at diagnosis. To move beyond the ill-defined category “high-risk multiple myeloma” which confers to ∼25% of all newly diagnosed patients, prospective studies are needed to dissect tumor biology and define multiple myeloma subtypes, and, based on biology, seek to define rational therapies for individual subtypes. This paper discusses novel insights and gives perspectives on diagnosis and MRD monitoring and future directions for prognosis and clinical management of multiple myeloma.

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Minimal Residual Disease Assessment in Myeloma

Dass

Kotwal

2019

Hematopathology

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Assessment of molecular remission rate after bortezomib plus dexamethasone induction treatment and autologous stem cell transplantation in newly diagnosed multiple myeloma patients

Cited by 15 publications

References 8 publications

Comparative analysis of minimal residual disease detection by multiparameter flow cytometry and enhanced ASO RQ-PCR in multiple myeloma

Comparative analysis of minimal residual disease detection by multiparameter flow cytometry and enhanced ASO RQ-PCR in multiple myeloma

New Developments in Diagnosis, Prognosis, and Assessment of Response in Multiple Myeloma

Minimal Residual Disease Assessment in Myeloma

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