Minimal residual disease and imaging‐guided consolidation strategies in newly diagnosed and relapsed refractory multiple myeloma

Abstract

Measurement of minimal residual disease (MRD) by next-generation flow cytometry (NGF) is an important tool to define deep responses in multiple myeloma (MM).However, little is known about the value of combining NGF with functional imaging and its role for MRD-based consolidation strategies in clinical routine. In the present study, we report our experience investigating these issues with 102 patients with newly diagnosed (n = 57) and relapsed/refractory MM (n = 45). Imaging was performed using either positron emission tomography or diffusion-weighted magnetic resonance imaging. In all, 45% of patients achieved MRD-negativity on both NGF and imaging (double-negativity), and 8% and 40% of patients were negative on either NGF or imaging respectively. Thus, in a minority of patients imaging was the only technique to detect residual disease. Imaging-positivity despite negativity on NGF was more common in heavily pretreated disease (four or more previous lines) compared to newly diagnosed MM (p < 0.01). Among the 29 patients undergoing MRD-triggered consolidation, 51% responded with MRD conversion and 21% with improved serological response. MRD-triggered consolidation led to superior progression-free survival (PFS) when compared to standard treatment (p = 0.04). In conclusion, we show that combining NGF with imaging is helpful particularly in patients with heavily pretreated MM, and that MRD-based consolidation could lead to improved PFS.

Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel

“…Beyond the sensitivity of next-generation methods that measure MRD inside the BM, the role of PET/CT to refine depth of response appears to be particularly valuable in RRMM due to the increased incidence of extramedullary disease ( 16 ). Accordingly, the presence of extramedullary disease after infusion with ide-cel was associated with inferior PFS in patients achieving undetectable MRD.…”

Prediction of Bone Marrow Biopsy Results From MRI in Multiple Myeloma Patients Using Deep Learning and Radiomics

“…Enabling individual, detailed monitoring of all local processes is urgently needed in MM, given the recent insights about the spatial heterogeneity and the spatiotemporal evolution of the disease, [18][19][20] as well as the recent evidence that functional whole-body imaging delivers complementary information to BM biopsies in minimal residual disease assessment of MM patients. [65][66][67]…”

“…Given the established link between local radiomics signatures and local tumor tissue characteristics, such machine learning models have the potential to inform on local tumor tissue characteristics multifocally across the complete BM, and thereby capture the spatially heterogeneous tumor manifestations and complex biological patterns observed in MM. Enabling individual, detailed monitoring of all local processes is urgently needed in MM, given the recent insights about the spatial heterogeneity and the spatiotemporal evolution of the disease, 18–20 as well as the recent evidence that functional whole-body imaging delivers complementary information to BM biopsies in minimal residual disease assessment of MM patients 65–67 …”

New Developments in Myeloma Treatment and Response Assessment

“…Rasche et al showed, in a large cohort, that 12% of patients found to be MRDnegative after induction therapy still had positive FLs on 18 F-FDG PET/CT analysis (110). Recently, a study by B€ ockle et al included 102 patients with newly diagnosed MM (n 5 57) and relapsed or refractory MM (n 5 45), who achieved a good partial response, a complete response, or a stringent complete response by International Myeloma Working Group 2016 criteria (111). Functional imaging ( 18 F-FDG PET/CT or diffusion-weighted MRI) was performed independently of bone marrow MRD results.…”