scholarly journals Prognostic Value of FDG-PET/CT Parameters in Patients with Relapse/Refractory Multiple Myeloma before Anti-CD38 Based Therapy

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4323
Author(s):  
Guillemette Fouquet ◽  
Myriam Wartski ◽  
Amina Dechmi ◽  
Lise Willems ◽  
Bénédicte Deau-Fischer ◽  
...  

Although anti-CD38 monoclonal antibodies have improved the prognosis of relapsed/refractory multiple myeloma (RRMM), some patients still experience early relapses with poor outcomes. This present study evaluated the predictive value of FDG PET/CT parameters for RRMM prior to initiating anti-CD38 treatment. We included 38 consecutive RRMM patients who underwent a PET/CT scan treated at our institution at relapse. The median PFS was 12.5 months and the median OS was not reached. 42% of the patients had an initial ISS score of 1, 37% of 2, and 21% of 3. The presence of >3 focal lesions (FLs, n = 19) and the ISS score were associated with inferior PFS (p = 0.0036 and p = 0.0026) and OS (p = 0.025 and p = 0.0098). Patients with >3 FLs had a higher initial ISS score (p = 0.028). In multivariable analysis, the ISS score and >3 FLs were independent prognostic factors for PFS (p = 0.010 and p = 0.025 respectively), and combined they individualized a high-risk group with a median PFS and OS of 3.1 months and 8.5 months respectively vs. not reached for the other patients. The presence of >3 FLs on PET was predictive of survival outcomes in patients with RRMM treated using CD38 targeted therapy. Combined with the initial ISS, an ultra-high-risk RRMM population can thus be identified.

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Hee Jeong Cho ◽  
Sung-Hoon Jung ◽  
Jae-Cheol Jo ◽  
Yoo Jin Lee ◽  
Sang Eun Yoon ◽  
...  

AbstractIn multiple myeloma (MM), a high number of focal lesions (FL) detected using positron emission tomography/computed tomography (PET/CT) was found to be associated with adverse prognosis. To design a new risk stratification system that combines the Revised International Staging System (R-ISS) with FL, we analyzed the data of 380 patients with newly diagnosed MM (NDMM) who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis. The K-adaptive partitioning algorithm was adopted to define subgroups with homogeneous survival. The combined R-ISS with PET/CT classified NDMM patients into four groups: R-ISS/PET stage I (n = 31; R-ISS I with FL ≤ 3), stage II (n = 156; R-ISS I with FL > 3 and R-ISS II with FL ≤ 3), stage III (n = 162; R-ISS II with FL > 3 and R-ISS III with FL ≤ 3), and stage IV (n = 31; R-ISS III with FL > 3). The 2-year overall survival rates for stages I, II, III, and IV were 96.7%, 89.8%, 74.7%, and 50.3%. The 2-year progression-free survival rates were 84.1%, 64.7%, 40.8%, and 17.1%, respectively. The new R-ISS/PET was successfully validated in an external cohort. This new system had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely.


2019 ◽  
Vol 213 (4) ◽  
pp. 918-924 ◽  
Author(s):  
Yoshiaki Abe ◽  
Kentaro Narita ◽  
Hiroki Kobayashi ◽  
Akihiro Kitadate ◽  
Masami Takeuchi ◽  
...  

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1878-1878
Author(s):  
Adriana C Rossi ◽  
Tomer M Mark ◽  
Kevin Wood ◽  
Roger N Pearse ◽  
Faiza Zafar ◽  
...  

Abstract Background Conventional radiography remains the gold standard imaging modality for staging multiple myeloma (MM). Other imaging modalities have been evaluated in recent years, and been shown to provide additional information about disease burden and location. FDG-PET/CT has proven to be useful in the identification of extramedullary disease and in monitoring patients with non-secretory myeloma. In addition to diagnostic utility, FDG-PET/CT has also been shown to predict time to relapse in the setting of newly diagnosed MM. However, to our knowledge its utility as a prognostic indicator in relapsed or refractory disease has not been studied. Methods We conducted a retrospective analysis of 61 patients with relapsed or refractory multiple myeloma (RRMM) who underwent PET/CT imaging prior to receiving salvage chemotherapy on a therapeutic trial of ClaPD (clarithromycin, pomalidomide, dexamethasone). Patients were heavily pre-treated, having received a minimum of 3 prior lines of therapy (range 3-15). All imaging was performed on the same PET/CT system at a single institution. Each PET/CT was evaluated in blinded fashion by two independent nuclear medicine physicians, with attention to the number and type of lesion, maximum SUV, and presence or absence of extramedullary disease. Disease response evaluation was performed monthly, and measured according to the international uniform response criteria. Multivariate analysis was performed to assess relationships of the above variables to depth of response, progression free survival (PFS), and overall survival (OS). Results Of 61 evaluable patients, 23 (38%) had no lytic lesions, 12 (20%) had <5 lytic lesions, and 26 (42%) had >5 lytic lesions on FDG-PET/CT. It is worth noting that 10 patients (16%) were found to have extramedullary disease, 8 of whom had >5 lytic bone lesions. There was no correlation between FDG-PET/CT findings and depth of response or median PFS, however patients with >5 lytic lesions had a median OS of 5.8 months, while it has not yet been reached for the other groups. At a median follow up of 13.2 months, 17 patients (74%) with no lytic lesions and 7 (58%) of those with <5 lytic lesions are alive. Conclusions The presence of >5 lesions on PET/CT at time of relapse is associated with poor prognosis in our cohort of heavily pre-treated patients with relapsed or refractory multiple myeloma receiving salvage chemotherapy with ClaPD. The presence of extramedullary disease, seen mostly in patients with >5 lesions, may contribute to our findings. Further studies in patients with relapsed or refractory MM are needed to evaluate the prognostic utility of FDG-PET/CT in this setting, as well as to extend these findings to other salvage regimens. Disclosures: Rossi: Celgene: Speakers Bureau. Mark:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Zafar:Celgene: Speakers Bureau; Millennium: Speakers Bureau; Onyx: Speakers Bureau. Pekle:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Niesvizky:Millennium: The Takeda Oncology Company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-20
Author(s):  
Elizabeth Hill ◽  
Baris Turkbey ◽  
Evrim Turkbey ◽  
Candis Morrison ◽  
Peter Choyke ◽  
...  

Introduction Whole-body magnetic resonance imaging (WB-MRI), including multiplanar multisequence technique with diffusion weighted images, is a novel imaging technique being evaluated for patients with multiple myeloma (MM). WB-MRI is ideal for this population due to its high sensitivity for bone marrow signal changes and full anatomic coverage from vertex to mid-thighs. It is well established that patients with unequivocal focal lesions on MRI have worse outcomes. Currently the IMWG recommends that all patients with smoldering multiple myeloma (SMM) undergo WB-MRI (or whole spine MRI if WB-MRI is not available) to rule out two or more focal lesions which would classify the patient as having symptomatic myeloma requiring treatment. There is a clear benefit of using MRI for the detection of early focal myeloma lesions however less is known about findings in the SMM population. Detection of subtle findings such as one small focal lesion or heterogeneous bone marrow in WB-MRI has unknown clinical significance that needs to be further evaluated. This study aimed to evaluate the sensitivity of WB-MRI compared to other highly sensitive functional imaging modalities in patients with SMM both at baseline and after treatment. Methods Imaging of patients with WB-MRI performed at the National Institutes of Health Clinical Center Myeloma Program were reviewed and compared to whole spine MRI and 18F-FDG PET/CT completed at the same timepoint. The majority of patients were being evaluated for enrollment on clinical trials. Patients had undergone a WB-MRI with a 3-Tesla system either as a baseline study, after completion of induction treatment, or during follow up determined by the time DWI became available at our institution. The imaging protocol included sagittalT1 weighted (W) and Short tau inversion recovery (STIR) for spine and coronal, axial T1W and axial T2 TSE pulse sequences. The functional component included diffusion weighted imaging in the axial plane (b=0 and 900sec/mm2). Radiological interpretation was performed by two readers using myeloma response assessment and diagnosis system (My-RADS) {Messiou, 2019 #340}. WB-MRIs were categorized as positive if focal lesions or diffuse/heterogenous pattern of bone marrow infiltration were present. Similarly, 18F-FDG PET/CTs and whole spine MRIs were classified as positive if focal lesions or diffuse/heterogenous pattern of bone marrow were present. Results A total of 34 patients with SMM and 5 patients with relapsed refractory multiple myeloma (RRMM) had sequential WB-MRI and 18F-FDG PET/CT. Figure 1 summarizes the radiological data of the SMM population. Eleven of these patients had PET/CT, whole spine MRI, and WB-MRI at baseline. Twenty-five patients had PET/CT and WB-MRI completed after at least 8 cycles of treatment. Thirteen patients had consistently negative imaging at baseline, 7 of which also had negative imaging after treatment, while 2 patients were found to have new lesions seen on WB-MRI after treatment. Six patients had resolution of positive imaging seen at baseline after treatment. Among the 17 patients with a positive WB-MRI, 12 (71%; 95% CI 47% - 87%) had a negative correlating PET/CT. Among 5 patients with positive PET/CT at the same time point as a WB-MRI, only 1 (20%; 95% CI 2% - 64%) correlated to a negative WB-MRI. Figure 2 depicts findings from patients with RRMM for comparison. All imaging modalities showed multiple focal findings in all 5 patients. Conclusions This study depicts the high sensitivity of WB-MRI in the SMM population. Such a high sensitivity is especially needed in SMM and early myeloma when disease burden is lower and the decision for treatment is being considered. In comparison to the RRMM population where all three imaging modalities easily detect multiple focal lesions, WB-MRI tends to identify myeloma involvement in the SMM patients more than the other imaging techniques. This suggests the importance of utilizing WB-MRI when diagnosing SMM. In the SMM population, the prognostic significance of lesions that are discrepant between MRI and FDG PET/CT is not yet known. Further follow up is needed to evaluate any difference in hard endpoints such as progression free survival between patients with positive findings described by WB-MRI. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
G. Fouquet ◽  
M. Wartski ◽  
A. Dechmi ◽  
L. Willems ◽  
B. Deau‐Fischer ◽  
...  

2017 ◽  
Vol 3 (1) ◽  
pp. 20 ◽  
Author(s):  
Kornelia Kajary ◽  
Zsuzsa Molnár

<p>To evaluate the role of FDG PET/CT before and after the treatment of multiple myeloma (MM) in our clinical practice, data from 32 patients (before therapy: 10 patients; after therapy: 22 patients) and from 46 examinations (before therapy: 10; after: 36) with a median time of follow-up of 24 months (before the therapy) and 26 months (after the therapy) were evaluated. FDG PET/CT positivity was characterized by SUVmax &gt;2.5, SUVmax &gt;4.2, focal lesions (FLs) &gt;3, and presence of extramedullary disease (EMD). The median progression-free survival (PFS) and the median overall survival (OS) for FDG PET/CT positive patients were shorter than for negative patients, according to all parameters. Before the therapy, significant correlation was found only between PFS and the number of FLs (<em>p</em> = 0.033). After the treatment, significant correlation was found between PFS and SUVmax (cut-off value 2.5: p &lt; 0.001; cut off value 4.2: p &lt; 0.001), between PFS and the number of FLs (<em>p</em> = 0.009), and between PFS and the presence of EMD (p &lt; 0.001). Significant correlation was found between OS and SUVmax (cut-off value = 2.5, <em>p</em> &lt; 0.001 and 4.2, <em>p</em> = 0.009), between OS and the number of FLs (<em>p</em> = 0.007), and between OS and the presence of EMD (<em>p</em> = 0.022). Our results confirmed the reliability and good prognostic value of FDG PET/CT in MM.</p>


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1384
Author(s):  
Anne-Victoire Michaud-Robert ◽  
Bastien Jamet ◽  
Clément Bailly ◽  
Thomas Carlier ◽  
Philippe Moreau ◽  
...  

Multiple myeloma (MM) is a haematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow. MM is associated with high morbidity and mortality and variable survival, which can be very short for some patients but over 10 years for others. These differences in survival are explained by intra- and inter-tumoral heterogeneity and demonstrate the potential benefits of adapting the treatment course for high-risk patients with a poorer prognosis. Indeed, identification of these high-risk patients is necessary and is based on the identification of high-risk biomarkers including clinical variables, genomics and imaging results. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a reliable technique for the initial staging of patients with symptomatic multiple myeloma (MM), and has been included in the IMWG (International Myeloma Working Group) recommendations in 2019. According to clinical studies, FDG-PET/CT characteristics could be used to define high-risk patients at initial diagnosis of symptomatic MM. The goal of this review is to demonstrate the prognostic value of FDG-PET in symptomatic MM patients, particularly in identifying high-risk patients, and thus, to best adapt therapeutic management in the future.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5622-5622
Author(s):  
Brian Østergaard ◽  
Julie R. Mortensen ◽  
Anne L Nielsen ◽  
Jon T. Asmussen ◽  
Oke Gerke ◽  
...  

Abstract Introduction: FDG-PET/CT is a promising methodology for staging, prognostication, and response evaluation in multiple myeloma (MM). The number of focal FDG lesions and the intensity of FDG uptake (standard uptake value, SUV) at diagnosis are informative of disease aggressiveness. Osteolytic bone disease is a hallmark of MM. Hypothetically; increased focal metabolic activity will precede, induce and correlate to osteolytic lesions. We aimed to elucidate the association between focal FDG positive lesions and osteolytic bone disease in MM patients. Methods: Twenty-two newly diagnosed MM patients, 16 males and 6 females aged 53-81years, were prospectively enrolled and studied with a standardized baseline FDG-PET/CT at diagnosis. A nuclear medicine and a radiology specialist evaluated the PET and CT parts separately and independently. Focal FDG positive lesions were assessed by dedicated software (ROVER™, ABX, Germany) to yield volume and SUV measures. All osteolytic lesions identified on CT were noted by size and localization. Results: FDG-PET and CT together identified a total of 390 lesions. We found more osteolytic lesions on CT (335) than FDG-positive lesions (169); the concordance between the modalities was 30%. 34% (114/335) of lytic lesions were FDG-positive, whereas ⅔ (114/169) of focal FDG-PET positive lesions were lytic according to CT. We found a significant correlation between higher FDG uptake measured as SUVpeak and osteolytic lesions >10 mm, and focal lesions with high FDG uptake had more pronounced osteolysis than focal lesions with less FDG uptake. Still sparse follow-up data did not allow analysis of the predictive value of focal PET positivity and the risk of development of future osteolysis. More compulsive data will be presented at the meeting. Conclusion: FDG-PET/CT offers dual information including metabolic activity (FDG-avidity) and degree of lytic bone disease (low dose whole body CT) in MM. About ⅔ (221/335) of osteolytic lesions were FDG-negative, whereas ⅔ (114/169) of FDG-positive lesions had a lytic component. Disclosures Plesner: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3543-3543
Author(s):  
Camila Mosci ◽  
Fernando Vieira Pericole ◽  
Allan de Oliveira Santos ◽  
Mariana Cunha Lima ◽  
Elba Cristina Camargo Etchebehere ◽  
...  

Abstract Introduction: Multiple myeloma (MM) is a plasma cell neoplasm, characterized by plasma cell infiltration inside the bone marrow, secretion of monoclonal immunoglobulin (paraprotein), and end organ damage including lytic lesions in the bones. About 80-90% of myeloma patients suffer from osteolytic lesions during the course of the disease. 18F-FDG PET/CT is an imaging technique capable to detect active disease in patients in multiple myeloma (MM) and can be helpful in staging and prognosis. However, its routine use is still hampered by several factors, including high cost, reimbursement issues, lack of cost-effectiveness studies and limited availability. 99mTc-sestamibi (MIBI) has also been proposed as a potential tracer in MM evaluation and is more accessible with lower costs. The aim of this study was to compare these two imaging modalities at staging disease and their relation with clinical data. Materials and Methods: Sixty-four patients with newly diagnostic MM (30 male; 34 female) were submitted to 18F-FDG PET/CT and 99mTc-Sestamibi SPECT/CT before treatment. Whole body PET/CT images were acquired 60 minutes after FDG administration and anterior and posterior whole-body scans (WBS) plus SPECT/CT of chest and abdomen were obtained 10 minutes after MIBI injection. Number of focal lesions, bone marrow involvement, contiguous soft tissue impairment and extra osseous lesions were recorded. Number of focal lesions was classified in 3 groups: 0 (no lesions); 1 (1-3 lesions); 2 (4-10); 3 (more than 10). A visual degree of uptake was defined for bone marrow involvement: comparison to liver on PET/CT and to myocardium on MIBI. Standardized uptake value (SUVmax) of the hottest lesion of each patient was registered. Potentials factors contributing to progression-free survival (PFS) were assessed with Cox regression model combining baseline clinical data (including renal function, anemia, hypercalcemia, LDH, bone marrow plasma cell percentage and ISS (I, II or III)) along with PET/CT and MIBI scan status. Results: PET/CT was positive in 61 patients (95%) and MIBI in 59 subjects (92%; P = 0.15). WBS was positive in 56 patients while WBS plus SPECT/CT was positive in 59 (p= 0.08). PET/CT detected extra osseous lesions in 4 patients and sestamibi in 1 subject. Contiguous soft tissue involvement was found in 29 and 24 patients on PET/CT and MIBI, respectively (p=0.05). PET/CT detected much more focal lesions than MIBI: 13, 11, 16 and 24 patients were in group 0, 1, 2 and 3 on PET/CT and 30, 18, 6 and 10 were on the same groups respectively on MIBI (p: 0.0001). In the figure below, a comparison between 99mTc-Sestamibi WBS (A) and 18F-FDG PET/CT (B) at staging in a 67 years-old male. SUVmax were statistically different in subjects who presented elevated LDH (p= 0.02). Seventy-five percent and 100% of patients with elevated LDH had contiguous soft tissue involvement on MIBI and PET/CT respectively. More focal lesions on PET/CT were found in patients with hypercalcemia (p=0.02), however this correlation was not observed on MIBI (p=0.45). Renal insufficiency was a negative prognostic factor for PFS (HR: 2.25). The same was observed with advanced ISS staging (HR: 4.29). However, only advanced ISS staging (III) and extramedullary disease detected by MIBI were independent predictors of worse PFS. Conclusion: There was no difference in the detection of active disease when comparing FDG PET/CT and MIBI SPECT/CT in MM staging, although the first one detected more number of lesions. Including SPECT/CT to planar images on MIBI did also not improve the number of positive scans. Elevated LDH and hypercalcemia were the only clinical parameters related to higher number of bone lesions while ISS staging (III) and extramedullary disease detected by MIBI were independent predictors of worse PFS. Our study demonstrated that sestamibi WBI detects less volume of disease compared to PET/CT, however it may substitute PET/CT in centers where it is not available or there is no reimbursement for MM staging. Figure. Figure. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8012-8012
Author(s):  
Martin F. Kaiser ◽  
Nuria Porta ◽  
Bhupinder Sharma ◽  
Daniel Levine ◽  
Dow-Mu Koh ◽  
...  

8012 Background: Early and sensitive detection of bone marrow disease and stratified patient management according to clinical risk can confer survival advantages in multiple myeloma (MM). Whole body MRI (WB MRI) and Fluorodeoxyglucose (FDG) PET/CT are included in international guidelines for imaging in patients with a suspected diagnosis of MM. However prospective studies comparing detection of MM by contemporary WB MRI as per recent MY-RADS consensus against FDG PET/CT are lacking. We report here protocol-defined endpoints from the prospective iTIMM (NCT02403102) study, comparing WB MRI and PET/CT, their relationship with serum and bone marrow estimates of disease burden, as well as molecular tumor characteristics. Methods: Patients with newly diagnosed MM or at first relapse planned to receive chemotherapy and autologous stem cell transplantation were enrolled in iTIMM. Matched baseline WB MRI and FDG PET/CT were performed and baseline clinical data including tumor genetics collected. Scans were double reported for presence of focal and diffuse disease by expert MRI and PET/CT radiologists, blinded to each other’s assessment. Paired methods were used to compare burden and patterns of disease on WB MRI compared to FDG PET/CT at baseline. Primary and secondary trial endpoints include relationship between post-treatment WB MRI response and progression-free survival, for which follow-up is ongoing. Exploratory endpoints include comparison of baseline WB MRI and PET/CT and their correlation with laboratory parameters, for which data is complete and reported here. Results: From May 2015 to March 2018, sixty patients (35 male; mean age 60 years) underwent baseline WB MRI as per MY-RADS consensus and FDG PET/CT. At least one focal lesion was detected in 50/60 patients (83.3%) by WB MRI and in 36/60 patients (60%) by PET/CT. WB MRI was more sensitive ( P< 0.05) across anatomical regions except for ribs and cervical spine. Four patients in our study showed two or more focal lesions ≥5 mm only on WB MRI but not PET/CT. All lesions detected by WB MRI but not PET/CT resolved in follow-up scans after treatment, excluding false positives. In 49/60 (81.7%) patients, diffuse disease was detected by WB MRI, compared to 10/60 (16.7%) by PET-CT; WB MRI was more sensitive across all anatomical areas ( P< 0.05). Plasma cell infiltration and paraprotein levels were significantly higher for patients with diffuse disease on WB MRI, but not on PET/CT. All genetically high-risk tumours, defined by t(4;14), t(14;16), del(1p), gain(1q) or del(17p), showed diffuse infiltration on WB MRI. Conclusions: WB MRI increases detection of focal and diffuse disease compared with FDG PET/CT, including improved detection of focal lesions meeting criteria for active disease as per International Myeloma Working Group diagnostic criteria, proposing it as a gold standard for tumor imaging in MM. Clinical trial information: NCT02403102.


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