The Role of PET/TC in the Full Range of Monoclonal Gammopathies

Abstract

Positron emission tomography (PET) with 18fluorine-fluoro-deoxyglucose (FDG) integrated with computed tomography (PET/CT) is a functional imaging technique helping us to assess bone marrow infiltration as well as unsuspected disease sites involving the bones and/or extramedullary sites. PET/TC has proved to be an independent prognostic factor for overall survival (OS) in symptomatic multiple myeloma (MM)(Zamagni,2011). However, its role in other monoclonal gammopathies (MG) is still a matter of debate. We have prospectively analyzed the contribution of baseline PET/TC in a unselected consecutive series of 158 patients with MG, including 88 MM, 7 MM smoldering (MMS), 11 Waldenstršm's macroglobulinemia (WM), 3 WM smoldering (WMS), 3 solitary bone plasmacytoma (SBP) and 46 monoclonal gammopathy of uncertain significance (MGUS). Patients with only palliative care were excluded. The pattern of bone marrow uptake on PET/TC was described as negative (NEG), diffuse involvement (DI) or focal lesions (FLs). Patients with more than 3 FLs as well as the presence of extramedullary disease (EMD) were analyzed separately. Overall survival (OS) was estimated by the Kaplan-Meier method. The main characteristics of PET/TC findings according to the type of MG are shown in Table 1. PET/TC was positive in 70 (79,5 %) of MM and 8 (72,7%) of WM. PET/TC was NEG in 100 % of MMS, WMS and SBP (except for the primary lesion). In MGUS, the findings reflect the clinical heterogeneity of this group: 19,6 % had bone disease (all but one case of probable inflammatory etiology), 17,4 % positive lymphadenopathy, 15,2 % lung disease (infection, fibrosis, pulmonary nodules), 6,5 % splenomegaly, 6,5 % liver disease, 6,5 % positive uptake in adrenal gland and other organs such as thyroid, stomach, colon or skin were affected less frequently. Median age of MM patients was 62 years (12-91), 51 men and 37 women (42%), the distribution according ISS was I (36,5 %), II (28,2 %) and III (35,3%). Among PET-positive MM, 39 (55,7 %) had >3 FLs, 17 (24,3 %) 3 or less FLs and 14 (24,3 %) DI. Median OS was 40 months, not reached (NR) and 85,7 months, respectively (p=ns). Mean bone marrow plasma cells in the >3 FLs group vs 3 or less FLs was 25 vs 12 (p=0,028). EMD was present in 13 (18,6 %) of PET-positive MM. Response with PET/CT was available in 32 patients: 18 achieved CR, 8 PR and 8 progressed. OS was NR for CR and PR vs 40 months (p <0,0001). In WM, patients with NEG or FL had NR OS vs 26 months in those with DI (p=0,16). PET/CT is positive in the majority of MM and WM patients, helping to separate patients with true indolent disease. At baseline, PET/TC is a useful tool to improve prognostic assessment in patients with MG. MM with >3 FLs or EMD at baseline had a trend towards lower OS. Negative serial PET/CT in MM is associated with favorable prognosis. Table SEQ Tabla \* ARABIC 1. Characteristics of main PET/TC findings according to the type of MG Type MM MMS WM WMS SBP MGUS n 88 7 11 3 3 46 Positive n /% 70/79,5 0 8/72,7 0 0 9/19,6 ->3 FLs 39/55,7 0 0 0 0 0 -3 or < FLs 17/24,3 0 1/12,5 0 0 1/2,2 -DI 14/20 0 5/62,5 0 0 1/2,2 -EMD 13/18,6 0 0 0 0 0 -Adenopathy 2/2,9 2/28,6 2/25 0 0 8/17,4 -Spleen 3/4,3 0 1/12,5 0 0 3/6,5 MG: Monoclonal gammopathy; MM: Multiple myeloma symptomatic; MMS: Smoldering myeloma; WM: Waldenstršm's macroglobulinemia; WMS: Smoldering Waldenstršm's macroglobulinemia; SBP: Solitary bone plasmocytoma; MGUS: Monoclonal gammopathy of uncertain significance; FL: Focal lesion; DI: Diffuse involvement; EMD: Extramedullary disease. Disclosures No relevant conflicts of interest to declare.

Positron Emission Tomography with Integrated Computed Tomography in Multiple Myeloma: A Silent Revolution

“…The role of PET/CT in the assessment of response to therapy, including SCT, has been emphasized [18][19][20][21]. In our recent study analyzing 88 MM patients [10], we demonstrated a significant impact of PET/CT in overall survival curves when patients who achieved partial or complete response to induction therapy were compared with those who showed disease progression. Although patients with baseline PET/CT positive findings (EMD, more than three focal lesions or diffuse involvement) usually show worse survival curves than negative cases, the difference did not reach statistical significance, likely due to a short follow-up.…”

“…A growing body of evidence supports the use of PET/CT in the assessment of diagnosis, prognosis and follow-up of MM patients, including concern about stem cell transplantation (SCT). The role of PET/CT in MM and related disorders has been recently reviewed [9] but little is known about the value of this technique in the assessment of monoclonal gammopathies other than active MM [10]. On the other hand, the correct diagnosis and risk of progression of precursor diseases can also be evaluated by PET/CT [11][12][13].…”

“…A study by the Spanish Group of Myeloma aiming to find the role of PET/CT on the risk of progression to MM is on-going. In a single institution study, we have analyzed the baseline findings of PET/CT in 158 patients with monoclonal gammopathies [10]. We were able to identify MM-related bone disease in 80% of symptomatic MM, but 100% of smoldering MM were negative.…”