SUVmax is a new prognostic indicator for patients with newly diagnosed MM

Multiple myeloma (MM) is a heterogenous disease that requires identification of patients with high-risk disease in order to adapt treatment strategies to improve overall outcomes. Positron emission tomography (PET)/computed tomography (CT) using 18F-deoxyfluoroglucose (FDG) has potential for being used as a staging tool for patients newly diagnosed with MM. A study by Anne-Victoire Michaud-Robert and colleagues, published in Cancers, described the use of SUVmax to quantify glucose metabolism and predict survival in patients with MM.¹

Methods and patients

This study analyzed retrospectively two large prospective phase III trials conducted in Europe: IFM2009 (NCT01191060) and EMN02/HO95 (NCT01208766). A total of 227 transplant eligible, newly diagnosed patients were included and the baseline characteristics are shown in Table 1. In the EMN02/HO95 trial, treatment with an autograft was favored in 67.7% of patients whereas in IFM2009, 45.5% underwent this therapy (p < 0.001). Overall, 41.4% of patients received bortezomib.

Table 1. Patient baseline characteristics¹

All baseline FDG-PET/CT images were re-evaluated centrally for the purpose of this analysis according to the following criteria:

• ‘Number, location, and SUVmax of focal lesions (FLs), defined as the presence of areas of focally increased tracer uptake on bone, with or without any underlying lytic lesion on CT, and present on at least two consecutive slices (excluding uptake in relation to osteoarticular benign pathologies);
• Number, location, and SUVmax of extramedullary disease (EMD) defined as tracer uptake on tissue not contiguous to bone;
• SUVmax of bone marrow (BM), measured at the lumbar vertebrae (L3-L5) excluding FLs with a 3D rectangular-shaped region of interest;
• Bone SUVmax or highest SUVmax on bone analysis was also reported including FLs and BM uptake.’¹

These criteria are similar to previously published guidelines for PET/CT in MM.^2,3

Results

• Median follow-up from this study was 4 years (range, 2 months to 6 years).
• In terms of progression-free survival (PFS) there were 121 events, and for overall survival (OS) 48 events were recorded.
• FLs were present in 73% of patients at diagnosis on FDG-PET/CT and 7.5% of patients had EMD, as shown in Table 2. There was no significant difference in these values between the two studies.

Table 2. Characteristics of FDG-PET/CT parameters at baseline before harmonization¹

For the harmonization of data, they chose a statistical method used in radiomics called M-ComBat. Prior to this, bone marrow SUVmax (BM SUVmax) and bone SUVmax were found to be significantly different between the two studies (p < 0.0001 and p = 0.01, respectively).

Univariate analysis was performed following harmonization and age (p = 0.035) and male gender (p = 0.04) were found to negatively impact PFS. The presence of EMD was a negative prognostic factor with affected patients having a median PFS of 20 months compared with 48 months in those without (p = 0.033). Autograft treatment improved PFS compared with patients who did not receive a stem cell transplant (57 months compared with 43 months; p = 0.038).

In addition, shorter PFS and OS were significantly associated with higher values of FL SUVmax and bone SUVmax. Above a threshold of 2.9 baseline FL SUVmax, PFS was reduced. For bone SUVmax, the threshold was > 3.4, as shown in Table 3. FLs, bone, and BM SUVmax over the defined threshold were significantly associated with a shorted OS. In multivariate analysis, only bone SUVmax was significantly associated with shorter OS.

Table 3. Baseline variables significantly associated with PFS and OS¹

Conclusion

Bone SUVmax has shown to be a simple and effective tool for interpreting PET/CT and it is strongly associated with a poor prognosis in patients with MM. Both the presence of EMD and bone SUVmax were shown to be predictive of poor outcomes in patients with MM. EMD has been previously identified as a key prognostic indicator, and by using this factor alone, 17 patients were identified as being high-risk. When using bone SUVmax, however, 186 patients with high-risk disease were found. Therefore, this shows the value of the application of bone SUVmax to help staging patients and to allow for adapted treatment regimens to be used as necessary. PET/CT has the advantage of being able to identify bone and extramedullary lesions at the same time, unlike other staging methods. It should be noted that the threshold chosen for bone SUVmax of 7.1 is a higher threshold than the one that was used previously and will need to be validated in further studies.

The current Editorial Theme of the Multiple Myeloma Hub is focusing on how to identify and treat patients with high-risk MM. Read more information, here.