Abstract
With contemporary therapeutic strategies in multiple myeloma, heretofore unseen depth and rate of responses are being achieved. These strategies have paralleled improvements in outcome of multiple myeloma patients. The integration of the next generation of proteasome inhibitors and antibody therapeutics promise continued improvements in therapy with the expectation of consistent depth of response not quantifiable by current clinical methods. As such, there is a growing need to develop adequate tools to evaluate deeper disease response after therapy and to refine the response criteria including the minimal residual disease. Several emerging techniques are being evaluated for these purposes including multi-parameter flow cytometry, allele-specific oligonucleotide polymerase chain reaction, next-generation sequencing, and imaging modalities. In this review, we highlight the recent developments and evaluate advantages and limitations of the current technologies to assess minimal residual disease. We also discuss future applications of these methodologies in potentially guiding multiple myeloma treatment decisions.
Highlights
Multiple myeloma is a heterogeneous plasma cell neoplasm which remains all but incurable despite recent significant advances in its treatment with various proteasome inhibitors [1], immunomodulatory agents, monoclonal antibodies [2, 3], histone deacetylase inhibitors [4, 5], and widespread use of highdose melphalan followed by autologous hematopoietic cell transplantation (HCT) and maintenance therapy [6,7,8,9,10,11]
We focus on technologies such as multi-parameter flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS) to assess minimal residual disease (MRD) burden in the context of multiple myeloma treatment
This study demonstrated the predictive ability of multi-parameter FCM performed at 100 days after autologous HCT [27]
Summary
Multiple myeloma is a heterogeneous plasma cell neoplasm which remains all but incurable despite recent significant advances in its treatment with various proteasome inhibitors [1], immunomodulatory agents, monoclonal antibodies [2, 3], histone deacetylase inhibitors [4, 5], and widespread use of highdose melphalan followed by autologous hematopoietic cell transplantation (HCT) and maintenance therapy [6,7,8,9,10,11]. With increasing number of available therapeutic options in myeloma, probability of achieving CR and stringent CR (sCR) is steadily improving as shown in a recent frontline phase 1/2 study where a combination of carfilzomib, Curr Hematol Malig Rep (2016) 11:118–126 lenalidomide, and dexamethasone resulted in unprecedented sCR rate of 42 % with early clinical trials suggesting even greater depths of response in the near future [17] These excellent responses are not always sustained and many patients (if not all) experience disease progression or relapse primarily due to residual myeloma reservoir through environment-mediated drug resistance and/or the persistence of myeloma stem cells [18, 19]. We focus on technologies such as multi-parameter flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS) to assess MRD burden in the context of multiple myeloma treatment
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