Whole-body magnetic resonance imaging plus serological follow-up for early identification of progression in smouldering myeloma patients to prevent development of end-organ damage.

The definition of multiple myeloma (MM) was updated in 2014, with the intent to enable earlier treatment and thereby avoid appearance of end-organ damage at progression from smouldering multiple myeloma (SMM) to MM. The purpose of this study was to investigate to which extent the development of end-organ damage at progression to MM was reduced under the updated guidelines. In this prospective observational cohort study (ClinicalTrials.gov Identifier: NCT01374412), between 2014 and 2020, 96 SMM patients prospectively underwent whole-body magnetic resonance imaging (wb-MRI) and serological follow-up at baseline and every 6 months thereafter. A total of 22 patients progressed into MM during follow-up, of which seven (32%) showed SLiM-criteria only but no end-organ damage. Four (57%) of the seven patients who progressed by SLiM-criteria only progressed with >1 focal lesion (FL) or a growing FL, and three (43%) due to serum free light-chain-ratio ≥100. Fifteen (68%) out of 22 patients who progressed still suffered from end-organ damage at progression. The updated disease definition reduced the proportion of SMM patients suffering from end-organ damage at progression to MM by one third. wb-MRI is an important tool for detection of SMM patients who progress to MM without end-organ damage.

The Role of Low Dose Whole Body CT in the Detection of Progression of Patients with Smoldering Multiple Myeloma.

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by plasma cell bone marrow infiltration and end-organ involvement. Smoldering MM (SMM) is an intermediate clinical entity between MGUS and MM, with a risk of progression to symptomatic disease 10% per year. Bone disease is the most frequent symptom of MM, with ~90% of patients developing bone lesions throughout their disease course. Therefore, imaging plays a crucial role in diagnosis and management. Whole-body low-dose CT (WBLDCT) is widely available and has been incorporated in the latest diagnostic criteria of the IMWG. The purpose of this study was to evaluate the role of WBLDCT in the early identification of lesions in patients with SMM who progress solely with bone disease. In total, 100 asymptomatic patients were consecutively assessed with WBLDCT from July 2013 until March 2020 at baseline, 1-year after diagnosis and every 1 year thereafter. Ten percent of patients were identified as progressors with this single imaging modality. This is the first study to evaluate prospectively patients with SMM at different time points to identify early bone lesions related to MM evolution. Serial WBLDCT studies can identify early myeloma evolution and optimize disease monitoring and therapeutic strategies.

Current and potential applications of positron emission tomography for multiple myeloma and plasma cell disorders.

Fluorine-18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET) allows evaluation of elevated glucose metabolism in malignancies. There has been increasing interest in FDG PET/CT for plasma cell disorders since the International Myeloma Working Group outlined multiple applications of this imaging modality, including distinguishing smoldering myeloma from active multiple myeloma, confirmation of solitary plasmacytoma, and multiple indications in patients with known multiple myeloma, including determining extent of initial disease, monitoring therapy response, and detection of residual disease following therapy. The field of molecular imaging is now shifting focus from evaluation of metabolism to targeted evaluation of specific tumor markers. Targeted PET imaging targeted of CXCR4 and CD38 has advanced into translational clinical trials, bringing us closer to powerful imaging options for myeloma. In this review we discuss the current applications of FDG PET/CT in plasma cell disorders, as well as advances in targeted PET imaging.

Scleredema associated with immunoglobulin A-κ smoldering myeloma: a case report and review of the literature.

BACKGROUND: Scleredema is a rare sclerodermoid skin condition characterized by diffuse symmetrical thickening of the upper part of the body. Its association with monoclonal gammopathy and myeloma was recently described; very few cases have been reported to date. CASE PRESENTATION: A 66-year-old Sri Lankan woman who had been followed in a dermatology unit for 34 years with diffuse systemic sclerosis presented with an acute exacerbation of the skin disease. Absence of Raynaud's phenomenon; sclerodactyly; characteristic lung, gastrointestinal, and cardiac involvement of systemic sclerosis; and repeatedly negative antinuclear antibodies test results led to reevaluation for the possibility of scleredema. Skin biopsies from four body sites showed normal epidermis and thickened reticular dermis with swollen collagen bundles separated from one another by clear spaces, resulting in fenestration. The skin appendages were not atrophied or bound down. Alcian blue staining showed interstitial mucin deposition. Serum protein electrophoresis demonstrated an abnormal monoclonal band in the ß-region with a paraprotein level of 8.9 g/dl. Immunofixation showed an abnormal band in the γ-region consisting of immunoglobulin A and κ. Bone marrow biopsy revealed abnormal monoclonal plasma cells (15%) with multinuclearity. There was no evidence of end organ damage, and whole-body magnetic resonance imaging did not reveal any evidence of bone involvement. The patient's diagnosis was revised as scleredema type 2 associated with IgA-κ, and she was referred to a hemato-oncologist for chemotherapy, which led to significant improvement in the skin condition. CONCLUSIONS: Scleredema is a rare disorder that has an enigmatic, rare association with monoclonal gammopathy. Dermatologists should be aware of this rare but important association.