Challenges and opportunities in the assessment of measurable residual disease in multiple myeloma

Abstract

Summary Treatment response assessment in multiple myeloma (MM) relies on the detection of paraprotein in serum and/or urine, bone marrow morphology and immunohistochemistry. With remarkable advances in therapy, particularly in the newly diagnosed setting, achievement of complete remission became frequent, creating the need to identify smaller amounts of residual disease and understand their prognostic and therapeutic implications. Measurable residual disease (MRD) can be assessed primarily by flow cytometry and next generation sequencing and state‐of‐the‐art assays have sensitivity approaching 1 in 106 cells. This review discusses the existing challenges in utilizing MRD to inform management of MM and highlights open research questions and opportunities as MRD is more routinely incorporated into clinical practice for patients with MM.

Minimal Residual Disease in Multiple Myeloma: Current Landscape and Future Applications With Immunotherapeutic Approaches

“…At present though, 10 −6 seems to be the most optimal threshold for MRD detection, and current criteria are likely to be reconsidered based on this new evidence. In the same context, it is rationale that an updated version of response criteria would take advantage of the quantitative nature of the sensitive MRD assays and may stratify patients not only on the context of MRD positive and MRD negative but on the level of MRD positivity as well (86). This stratification would be helpful for deeper evaluation of treatment efficacy and may prove important for defining different therapeutic MRD-driven strategies based on the level of response to a previous regimen.…”

Autologous Transplantation Using Donor Leukocytes Loaded Ex Vivo with Oncolytic Myxoma Virus Can Eliminate Residual Multiple Myeloma

“… 6 , 9 Despite the advances in the treatment of MM, the disease is still considered incurable, and eventually patients relapse or become refractory to all available standard therapies. 10 One of the major failures of the available therapies is to control or eliminate MM minimal residual disease (MRD), 11 , 12 , 13 which occurs when myeloma cells that hide in niches within the BM become resistant to standard therapies and/or contamination of the autologous stem cell transplant graft with patient myeloma cells. 14 Therefore, more effective treatments are required in order to obtain sustained cancer-free outcomes, in particular by developing strategies to eliminate the MRD remaining after standard therapies have achieved their maximal disease burden reduction.…”

Aberrant Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts, Assessed by Next-Generation Flow Cytometry, Is a Negative Predictor for Deep Response Post Autologous Transplantation in Multiple Myeloma; A Prospective Study in 199 Patients

“…Of note, this correlation was stronger when we set MRD negativity and not CR as the clinical endpoint, thus implying that the absence of graft contamination could be a strong predictor of deep and lasting remissions. MRD negativity is a distinct and powerful independent prognostic factor in MM, which may overcome baseline prognostication by ISS and/or cytogenetics [31,32], and is currently considered as the main or secondary endpoint in several ongoing trials [33,34]. Therefore, the identification of biomarkers capable of an early prediction of MRD negativity is of utmost significance for the clinical management of MM patients and may confer significant surrogate information on modern tailored MRD-driven approaches [34,35].…”