In 2002, I published one of the first papers on the use of radioactive sugar (F18 fluorodeoxyglucose, or FDG) as an imaging agent in plasma cell disorders.  At that time, I was fortunate to work at one of the first centers investigating this technique (since 1996), which was at Cedars-Sinai Medical Center in Los Angeles. 

We already had several years’ follow-up and could report that patients with MGUS (monoclonal gammopathy of undetermined significance) had negative F18 scans, and patients with persistently positive scans had high-risk myeloma. Clearly, sugar uptake and retention (called “avidity”) was strongly correlated to myeloma disease activity.

One could also detect the presence or absence of myeloma lesions inside and outside the bone marrow (so-called “extramedullary disease”). One could thus distinguish between a solitary lesion (solitary plasmactyoma) and the presence of multiple lesions—myeloma!

New IMWG guidelines published

It is therefore particularly gratifying for me to see that 15 years later, the potential for FDG PET/CT scanning has been realized, with the April 1 publication in The Lancet Oncology of new consensus guidelines by the International Myeloma Working Group (IMWG) on the use of this extremely accurate imaging technique in 2017 and moving forward. A podcast interview with lead author Dr. Michele Cavo that accompanies the article and is posted on The Lancet's website reports the findings of the Bologna team.

The new IMWG guidelines provide a comprehensive review of the current role and optimal uses of FDG PET/ CT scanning. This combined technology is used to assess active myeloma using sugar uptake (FDG PET avidity: SUV—Standardized Uptake Value) and the presence or absence of associated bone destruction (CT scanning). CT scanning is only performed if an area of positive FDG uptake is found. Both elements are important in assessing the status of the myeloma.

Two key questions

The two key questions are: 1) Is there active myeloma anywhere inside or outside the bone? And 2) Has this active disease caused bone or tissue damage? The new guidelines summarize the situations in which such assessments are most useful.

FDG PET/CT scanning is useful throughout the course of the disease. To establish a diagnosis of  MGUS and early smoldering disease, the scan must have a negative result that shows no uptake of FDG. For patients with a single lesion, an FDG PET/CT is mandatory to exclude the presence of possible additional lesions. With successful therapy, active lesions disappear—often very rapidly!

An important new aspect is the documentation of NO lesions (FDG PET negative) combined with a negative minimal residual disease (MRD) test, using Next Generation Flow (NGF) or Next Generation Sequencing (NGS), in the bone marrow.  This demonstrates full MRD-negativity status inside and outside the bone marrow, now considered to be the crucial MRD-negative disease assessment.

Advantages versus disadvantages

As with all test methods, there are pros and cons. An important advantage is that there is scanning of the whole body, which is not easily feasible with other technologies, such as an MRI. Additionally,response can be detected very rapidly. In contrast, improvement in an MRI occurs slowly over a period of six to nine months. A bonus advantage is that FDG PET/CT also detects any second malignancy (so-called “SPMs”—such as breast, lung, colon, or prostate cancer, for example, which may be present).

Disadvantages include some cases in which active myeloma does not take up sugar (which is rare), and other cases in which areas of inflammation, infection, tissue damage or tissue healing may cause some uptake. Careful review of scans by experts is definitely required.

Myeloma defining event

In the New Diagnostic Criteria, MRI is used as a criterion of an MDE (myeloma defining event). Two or more lesions indicate the presence of myeloma versus smoldering or earlier disease. However, it is important to note that a positive PET/CT scan also qualifies as an MDE, especially if bone destruction is evident on the CT component. Thus, both MRI and/or PET/CT are valid and can be used in this setting. The IMWG is also assessing the role of WBLDCT (whole-body low-dose CT) alone as an early diagnostic tool. Initial results indicate that more than 20% of patients with negative routine X- rays (commonly referred to as a “skeletal survey”) have lesions discovered using the WBLDCT technique, which will probably become a new  standard of care for early screening.

Reimbursement

Since the value of scanning can usually be strongly justified, it is important for the treating physician both to be aware of the advantages and to push hard (with letters if necessary) for reimbursement coverage. The IMF has worked diligently with CMS/Medicare to endorse the need for FDG PET/CT imaging. The new guidelines represent strong ammunition to submit to skeptical insurers or coverage entities. The IMF and IMWG members are truly honored to collaborate with global experts who work so diligently to prepare excellent guidelines such as this, which clearly document  the optimal standard of care.