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positivity. In their study, 68% of patients remained posi- tive at the end of lenalidomide, bortezomib, and dexam- ethasone (RVD) induction, 42% after RVD consolidation and 25% after transplantation, with positivity being asso- ciated with an adverse outcome. In the TT3 study,5 the number of PET-FLs both at diagnosis and pre-transplant were important independent variables associated with adverse outcome.5 On multivariate analysis, more than 3 FLs at day 7 was associated with inferior OS and PFS, even in patients with GEP70 defined high risk. However, in TT3, we did not report the outcome of patients who sup- pressed their FL activity. The finding that these patients have outcomes similar to patients without FLs at diagnosis is of crucial clinical importance and suggests that treat- ment should be continued until lesion resolution.
Previous studies have shown that patients with a con- ventionally defined complete response using IMWG crite- ria may have persistence of the FLs after therapy.8,22 Such findings have led to the refinement of the IMWG defini- tions of complete response with the addition of assess- ment of MRD using flow cytometry, next generation sequencing, and imaging.2 Using an effective therapeutic strategy combining immunomodulatory drugs, protea-
some inhibitors, and transplant, we were able to demon- strate that imaging gives additional information to both the clinical assessment of response using the IMWG crite- ria and also to MRD detection using a flow cytometric approach sensitive to 1 in 10-5. The recent study by the IFM group4 showed similar findings with 14 of 86 patients being PET-CT positive at the same time as they were MRD negative, suggesting that both techniques are essen- tial to truly define a stringent response.
In other tumor settings, a PET-CT scan during therapy is used to guide treatment decisions, including continuing therapy, changing therapy to a modality with a different mechanism of action, or stopping treatment altogether. Initiating the individualization of therapy in myeloma based on a comprehensive disease assessment is one way to improve patient outcomes. This study suggests that a risk-adapted approach based on serial PET-CT analysis would be appropriate for myeloma patients as it can reli- ably identify a group of patients with poor prognosis at different stages of their therapy who may benefit from alternative therapy. On the basis of our results, serial PET- CT should be integrated into follow-up algorithms and risk-adapted clinical trials should be implemented.
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