The Role of PET Scan Imaging In Waldenstrom Macroglobulinemia

PET scan imaging has shown an important role in the diagnosis and prognosis of patient with lymphomas and even multiple myeloma. However, its role in Waldenstrom Macroglobulinemia (WM) has not been previously examined. In this study, we sought to determine the role of PET scan imaging in the diagnostic workup, post-treatment follow up and prognosis of patients with WM.

PET/CT scan imaging was evaluated among 12 newly diagnosed and 23 relapsed/refractory WM patients who were enrolled on the clinical trial 06–008 using bortezomib and rituximab therapy. Scans were defined as positive if any FDG uptake was present. We further delineated PET positivity into three subgroups (lymph nodes, hepatosplenomegaly, and skeletal uptake) by number of sites and intensity.

Among the 35 patients, 60% were males, 94% had an ECOG performance status of zero, and 51% were intermediate or high risk based on the Morel ISS-WM study (ISS-WM). Twelve (34%) were previously untreated, 7 (20%) had 1 line, 5 (14%) had 2 lines and 11 (31%) had 3 or more lines of therapy. At baseline, 27 (77%) patients were PET positive. Out of these, 19 (83%) were positive for PET scan uptake in the relapsed setting, while 8 (67%) were positive in the upfront setting. Head/neck/chest lymph nodes involvement was present in 20 (57%) patients (57% of relapsed/refractory, 58% of upfront), hepatosplenomegaly occurred in 10 (29%) patients (30% of relapsed/refractory, 25% of upfront) and skeletal uptake was seen in 17 (49%) patients (57% of relapsed/refractory, 33% of upfront). Post treatment, 11 of the 27 (41%; 90% CI: 25–57) PET positive patients had negative PET (7(37%) relapsed/refractory and 4(50%) upfront). Considering the three separate analyses of lymph nodes, hepatosplenomegaly, and skeletal: 11 of the 20 (55 %; 90% CI: 50–60) lymph nodes PET positive patients had negative PET (6(46%) relapsed/refractory and 5(71%) upfront); 6 of the 10 (60 %; 90% CI: 51–69) hepatosplenomegaly PET positive patients had negative PET (3(43%) relapsed/refractory and 3(100%) upfront); 10 of the 17 (59 %; 90% CI: 52–66) skeletal PET positive patients had negative PET (8(62%) relapsed/refractory and 2(50%) upfront). Furthermore, 4 (50%) patients who had a negative PET scan before treatment continued to have negative PET scans after completion of 6 cycles of therapy. On the other hands, 4 (50%) patients who had a negative PET scan before therapy became PET positive. The median percentage of bone marrow plasma cells was 42.5% among the 18 skeletal PET negative patients and 60% among the 17 skeletal PET positive patients (p-value: 0.0869). In these two groups of patients, 7 (39%) patients in the skeletal PET negative and 2 (12%) patients in the skeletal PET positive, less than 40% bone marrow plasma cells involvement was observed (p-value: 0.1182). When comparing PET scan results from before and after treatment, 15(43%) patients had a negative PET scan before starting treatment and the rest had low, intermediate or high uptake. Of these 12 (34%) had high uptake before treatment. After completing therapy, 26 (74%) patients had a negative PET scan and only 6 (17%) patients had a high uptake. In contrast, of the 2 patients who had a low uptake before treatment, 1 showed an improvement to a negative PET uptake and 1 showed increased uptake after treatment. Of the 6 patients who had a moderate uptake before treatment, 4 showed an improvement to a negative scan and 2 showed moderate or high uptake. Finally, of the 12 patients who had a high uptake before treatment, 6 improved to a negative scan, 2 to an intermediate scan and 4 remained stable at high PET uptake.

PET scans are a valuable tool for the diagnosis and assessment of response in patients with WM. Over 77% of patients have a positive scan at baseline in contrast to prior studies indicating that only 20% have positive measurements on CT scans. Most of the patients responded well after therapy with 41% of patients showing a negative PET scan after therapy. Negative scans correlate with response to therapy, indicating a possible role as a prognostic marker. Further evaluation of PET scans in WM is warranted.

Leleu:Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Ghobrial:Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.