The Diagnostic and Prognostic Utility of 18F-FDG PET/CT in Transplant Ineligible Multiple Myeloma Patients Receiving Novel Agents
Authors: Takeoka Yasunobu , Yamamura Ryosuke , Araki Taku , Inaba Akiko , Fujitani Yotaro , Koh Genju , Seura Hirotaka , Okamura Terue , Ohta Kensuke 
Published: October 2019

Abstract

Background
The value of 18F-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) in diagnosis and monitoring of multiple myeloma (MM) has been demonstrated predominantly in younger patients who are eligible for autologous stem cell transplantation. However, a majority of the MM patients are known to be transplant ineligible because of advanced age, comorbidity and/or frailness. Therefore, to evaluate the diagnostic and prognostic value of FDG- PET/CT in such patients is expected to contribute the physicians to design the more adequate personalized therapies.

Patients and Method
We reviewed the medical records of previously untreated symptomatic MM patients who were diagnosed at Osaka Saiseikai Nakatsu Hospital between February 2008 and June 2013. In this retrospective study, transplant ineligible patients who received FDG-PET/CT examination prior to the initial treatment were evaluated. A total of 48 patients (17 males and 31 females, median age of 71 years (range 47-91) were evaluable. IgG, IgA, BJP and non-secretory types were 35 (73%), 10 (21%), 1 (2%), and 2 (4%), respectively. The ISS stage 1, 2 and 3 comprised 15 (31%), 17 (35%) and 16 (33%), respectively. Closely after the FDG-PET/CT, all patients underwent the treatment including novel agents (bortezomib or lenalidomide). The results from FDG-PET/CT were evaluated and categorized by a team of experienced radiologists into three groups just according to the criteria proposed by Zamangni et.al. (Blood 2011;118:5989-5995): focal lesion (FL), diffuse lesion (DL), and extramedullary disease (EMD). And standard uptake value maximum (SUV max) was recorded. Imaging valuables of FDG-PET/CT were analyzed for association with other baseline parameters including types of serum or urinary M protein, serum levels of albumin (Alb), beta-2-microglobulin (B2M), C-reactive protein (CRP), lactate dehydrogenase (LDH), and CD19, 20 and 56 expressions in CD138 positive plasma cells in bone marrow. Furthermore, valuable combination of these parameters in predicting a clinical outcome of the patients was screened. A Kruskal-Wallis or Mann-Whitney U test was used to compare imaging variables in relation to baseline parameters. Kaplan-Meier analysis was used to estimate overall survival (OS). Univariate and multivariate analyses of prognostic factors were carried out using logistic regression.

Results
Of the 48 patients, 17% of the patients had a negative PET/CT scan before the treatments, 24% had 1 to 3 FLs, 59% had either DL or more than 3 FLs, and 9% had EMD. The serum levels of CRP, LDH, B2M, and Alb were 1.9 mg/L, 174 IU/L, 3.8 mg/L, and 37 g/L, respectively. A median SUV max was 3.7 in the all patients. As shown in Table 1, a median serum B2M level was significantly higher in patients with >3 FLs and/or DLs compared with 1-3 FLs (p=.014). A median SUV max significantly higher in patients with >3 FLs and/or DLs or EMD (p=.001). In addition, SUV max was significantly higher in patient with CD56-low, compared with CD56-high myeloma cells (8.0 vs. 3.3 p=.017). In a median follow up period of 20 months (range 2-67), 45, 10 and 45% of the patients received the treatments with lenalidommide, bortezomib and both, respectively. Estimated median OS of the all patients was 40 months (range 33-48). The ISS staging at the baseline did not significantly affect the OS. On univariate analysis, low serum Alb (Alb <35g/L) and high SUV max (SUV max>3.7) were unfavorable prognostic factors (p=.042 and p=.062, respectively). On multivariate analysis, the results from FDG-PET/CT did not significantly correlated with the OS. Interestingly, however, the OS for patients satisfying with both low Alb and high SUV max was significantly shorter than those with the other patients. (median 19 month vs. 45 month p=.029) (Figure1).

Conclusion
This study demonstrated that FDG-PET/CT at baseline can exactly evaluate tumor spread and variability. Furthermore, FDG-PET/CT in combination with other parameter was expected to provide additional information on making treatment strategy in transplant-ineligible MM patients receiving novel agents.

Disclosures:
No relevant conflicts of interest to declare.