Imaging in Multiple Myeloma - Independent review perspective for IMWG 2016 response assessment

As per the International Myeloma Working Group (IMWG) 2016 criteria, response evaluation in multiple myeloma takes into consideration two main components: clinical data (e.g., SPEP, UPEP, Immunofixation, etc.) and imaging-based plasmacytoma/ myeloma-lesions assessment. Independent central review of imaging and clinical data may be required for clinical trial submission. Currently, no clear guidance is available on acceptable imaging modalities and various types of myeloma lesions seen on imaging. The purpose of this abstract is to describe in detail how to perform and incorporate imaging assessment in a clinical trial charter; this will facilitate the independent review process as well as address the most common questions related to imaging assessment. Historically, a skeletal survey/radiography has been the most commonly used imaging modality to assess disease burden at screening and inconsistently at post-treatment for response assessment in patients with multiple myeloma. However, skeletal survey often displays low sensitivity and resolution in identifying myeloma-lesions. With the more widespread availability of newer imaging techniques, there has been a shift in the image evaluation paradigm towards the modalities with superior resolution and sensitivity for early detection of myeloma progression, such as whole-body low dose CT, whole-body MRI and FDG-PET. The advantages and disadvantages of each modality need to be considered when designing the evaluation criteria for multiple myeloma clinical trials, tailored to suit the needs of the trial. This is especially important in the response assessment of patients who are receiving novel targeted therapeutic agents. For instance, with more modern myeloma treatments where a rapid objective response is typically achieved, assessing the metabolic activity of lesions on FDG-PET/CT can prove more valuable than using a skeletal survey. Documenting the changes in metabolic activity of the disease can be useful in the early evaluation of response or progression. Medullary and extramedullary myeloma-lesions/plasmacytomas show a varied appearance on different imaging modalities. Therefore, it is important to assess all myeloma-lesions consistently across various investigator sites involved in a clinical trial. We propose to assess soft tissue myeloma-lesions, including medullary and extramedullary plasmacytomas as measurable (target) lesions and pure lytic bony lesions as non-measurable (non-target) lesions. This approach allows for quantitative assessment of measurable lesions and qualitative assessment of the rest of the disease burden. A consistent imaging assessment by a Musculoskeletal Radiologist can then be integrated with clinical data by an Oncologist for IMWG response assessment. This can result in a guide for imaging-based independent review assessment in multiple myeloma clinical trials