P-015: Is it time to revisit role of PET-CT imaging and its integration with other parameters in International Myeloma Working Group (IMWG) response assessment criteria?

Background The landscape of imaging in multiple myeloma has changed drastically since the publication of IMWG 2016 criteria. 18 F-FDG PET-CT (PET-CT) is being used more frequently, for staging, prognosis and clinical decision making. PET-CT is useful for both morphological and the metabolic activity of the plasma cells to predict and monitor clinical response. Studies have shown that subjects who achieved complete response by hematologic criteria but have PET positive lesions have poorer outcome. PET-CT has high sensitivity and specificity for detecting all lesions types. PET negativity has been equated to Minimal residual disease (MRD) negativity, and hence role of both positive and negative PET in IMWG response assessment need to be better defined. Until now extramedullary disease (EMD) and plasmacytoma evaluation have been the focus of response assessment in IMWG, although plasmacytoma is a histological, not an imaging diagnosis. Paramedullary lesions (lytic bone lesions with extraosseous soft tissue component), intramedullary lesions (soft tissue lesions in the medullary cavity) as well as pure lytic bone lesions have not been fully included in the evaluation. There is a need to better define various lesions and disease presentations seen on imaging in myeloma and their role in overall response. Additionally, role of different imaging modalities in clinical trials as well as a standardized imaging schedule, based on the presence of baseline disease burden, should be defined. The purpose of this study is to define and incorporate the imaging manifestations of myeloma of PET-CT into the IMWG criteria. A standardized PET-CT assessment approach is lacking in IMWG 2016, although Italian Myeloma Criteria for PET Use (IMPeTUs), has described PET-CT evaluation in detail, including the cut off for positivity and negativity, aligning it to 5-point Deauville Scoring (5PS). This study will also highlight the importance of PET-CT as a modality of choice in myeloma and provide a standardized methodology to integrate PET in overall assessment. We propose that myeloma lesions should be assessed in two broad categories, target (measurable) and non-target (non-measurable) lesions. Targets should include up to a total of six extramedullary and/or paramedullary lesions. Non-target lesions should include any additional measurable lesions, other soft tissue and bone lesions characteristic of myeloma, which do not meet criteria for target lesions. The status of these lesions along with any new lesions will drive an overall anatomical response. For PET-CT assessments, 5PS should be followed with liver as comparator for positivity. Metabolic responses like Complete metabolic response(CMR) etc. should be derived. An integrated imaging response can then be combined with clinical parameters to provide an overall IMWG response. This proposed guidance will help standardize integration of PET imaging in IMWG response assessment more efficiently and consistently across trials.