FDG PET Imaging in Multiple Myeloma: Implications for Response Assessments in Clinical Trials

F-fluorodeoxyglucose positron emission tomography integrated with computed tomography (F-FDG PET/CT) is an effective modality to assess disease burden, detect extra-medullary disease and monitor minimal residual disease (MRD) for multiple myeloma (MM) patients. This modality of imaging is incorporated in the International Myeloma Working Group (IMWG) response criteria that are widely used in MM clinical trials. Interpretative pitfalls are commonly encountered in F-FDG PET/CT studies and proper interpretation requires knowledge of the normal physiologic distribution of the tracer affecting available F-FDG for tumor tissue uptake. We describe a series of MM patients who exhibited a deep response to treatment, based on clinical features, serum markers and bone marrow (BM) biopsy. However, these patients seemed to have new lesions on post-therapy F-FDG PET/CT images which could be interpreted as progressive disease according to the IMWG criteria. Sequestration phenomenon, which is the disappearance of F-FDG sequestration by myeloma-infiltrated marrow after successful anti-myeloma therapy, could lead to unmasking of new F-FDG-avid lesions on post-therapy PET/CT due to higher F-FDG bioavailability to residual tumor tissue. Clinical correlation, awareness of the F-FDG sequestration in myeloma infiltrated BM and its impact on other F-FDG avid areas in the body are necessary to avoid potential pitfalls in end-of-treatment imaging interpretation. While considering patients for clinical trials, clinicians should be mindful of this sequestration phenomenon in the interpretation of post-therapy PET/CT imaging in MM patients with initially heavily infiltrated marrow.