scholarly journals FDG and FCH PET/CT of Multiple Myeloma at Various Clinical Situations: Lesion Detection, Proposal for a Patient-Based "Summ" Score and Reproducibility of Scoring

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4487-4487
Author(s):  
Jules Zhang-Yin ◽  
Sona Balogova ◽  
Mor Seny Gueye ◽  
Mohamad Mohty ◽  
Françoise Montravers ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Scoring System ◽  
M Protein ◽  
Single Patient ◽  
Radiotracer Uptake ◽  
Bone Marrow Uptake ◽  
Pet Ct ◽  
Consensus Reading ◽  
Initial Staging

Abstract Introduction: In a previous pilot study, PET/CT performed for suspected relapsing or progressive multiple myeloma (MM) revealed more lesions with FCH than with FDG. We then launched a prospective comparison of FDG and FCH PET/CT in MM at initial staging, restaging and during therapeutic follow-up. The IMPeTUs scoring system was proposed in 2016 by Nanni et al. to summarize the results of FDG PET/CT. However, the IMPeTUs scoring system is not designed to reflect by one single patient-based score the extent of the disease, as determined on radiotracer uptake. To compare the performance of those two PET radiotracers, we set a single patient-based score, derived from the IMPeTUs approach, and we applied it to the comparison of FDG and FCH PET/CT at various clinical situations of MM. Aim: To compare (1) the reproducibility of reading and scoring of FDG and FCH PET/CT in initial staging, restaging and therapeutic follow-up of MM, (2) the correlation between the scores on FDG or on FCH PET/CT and serum concentration of M-protein, a quantitative criterion reflecting the secretory activity of MM, recommended at diagnosis and as a part of evaluation of therapeutic response. Patients and methods: FDG and FCH PET/CT were performed in 105 patients (20 at initial staging, 37 at relapse and 48 during follow-up).The FDG and FCH PET/CTs were read in a random order with a wash out period by two experienced readers blinded to any patient's clinical data. They scored according to IMPeTUs scoring system, evaluating the number and intensity of foci of radiotracer uptake in 5 sites (spine, skull, extraspinal, visceral and nodal), the presence of diffuse axial and/or appendicular bone marrow uptake, of PET-positive lytic lesions, or of fractures. According to the number of visible foci in each site, the site-score was: 1: 0 focus, 2: 1-3 foci, 3: 4-10 foci or 4: >10 lesions. In case of diffuse bone marrow uptake by the axial or appendicular skeleton, the site-score 4 was attributed to the corresponding site, to integrate this pattern in one single score per site. A "SUMM" score, theoretically ranging from 5 to 20, was obtained by summing up the site-scores of the 5 sites. The kappa coefficient was calculated to evaluate the inter-reader agreement in determining the SUMM score.A consensus reading was finally performed, to solve discordances in scoring between the two readers. The paired Wilcoxon test was used to compare the consensual SUMM scores of PET/CT with FDG and FCH; the correlation coefficient between the consensual SUMM scores and M-protein level was calculated. Results:Before final consensus, the inter-reader agreement in determining the SUMM score was better with FCH (Kappa=0.90; CI=0.85-0.95) than with FDG (Kappa=0.75; CI=0.64-0.86). The analysis was then continued on the data of consensus reading. FCH showed more foci in 28 patients (4 at initial staging, 13 at relapse, 11 during follow up) and FDG in 14 patients (3 at initial staging, 4 at relapse, 7 during follow up). The SUMM score was significantly greater with FCH than with FDG (p=0.0027).M-protein was present in the serum of 95/105 patients. The correlation with serum M-protein level was significantly >0 for both SUMM scores, but loose for FDG (r=0.3, p=0.0029) and stronger for FCH (r=0.7, p<0.001), the difference being significant (p=0.0001).Among 8 patients without M-protein detected in their serum, a negative PET/CT with FDG (SUMM FDG=5) but positive with FCH (SUMM FCH>5) was observed in 2 patients (1 referred for evaluation of relapsing MM and in one referred during therapeutic follow-up of MM). Conclusion: A patient-based "SUMM" score is proposed to characterize the extension and the number of foci on PET/CT imaging of MM. Using this SUMM score, a better inter-reader reproducibility, lesion detectability and correlation with serum M-protein was observed for FCH than for FDG, confirming FCH as a potential tracer in MM deserving further research. Disclosures Garderet: Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy.

Additional value of integrated PET/CT over PET alone in the initial staging and follow up of head and neck malignancy

2010 ◽  
Vol 24 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Tomohiro Ishikita ◽  
Noboru Oriuchi ◽  
Tetsuya Higuchi ◽  
Go Miyashita ◽  
Yukiko Arisaka ◽  
...  
Keyword(s):  
Head And Neck ◽  
Head And Neck Malignancy ◽  
Neck Malignancy ◽  
Pet Ct ◽  
Additional Value ◽  
Initial Staging

Use of 18-F FDG PET / CT Scanning Into the First Follow Up of Patients with Multiple Myeloma and Association with Biochemical Response

2017 ◽  
Vol 17 (1) ◽  
pp. e149
Author(s):  
Mercedes Gironella ◽  
Juan Alfons Soler ◽  
Marc Simó ◽  
Carlos Palacio ◽  
Julia Montoro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Fdg Pet ◽  
Ct Scanning ◽  
Biochemical Response ◽  
Pet Ct ◽  
Fdg Pet Ct

Imaging techniques used in the diagnosis, staging, and follow-up of patients with myeloma

2005 ◽  
Vol 46 (7) ◽  
pp. 716-724 ◽  
Author(s):  
M. E. Mulligan
Keyword(s):  
Imaging Techniques ◽  
Staging System ◽  
Review Article ◽  
Imaging Modalities ◽  
Resonance Imaging ◽  
Advanced Imaging ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Initial Staging

Radiologists play a central role in the diagnosis, initial staging, follow-up, and restaging of patients with myeloma. This review article attempts to familiarize the reader with all the various types of myeloma, their imaging appearances and useful imaging strategies. The staging system for myeloma patients has been updated and now includes findings from advanced imaging modalities. Radiologists have a vast array of imaging modalities at their disposal to aid them in diagnosis, staging, and follow-up. Currently, conventional radiographic skeletal surveys, magnetic resonance imaging, and F-18 FDG PET/CT examinations are the most useful instruments.

The Utility of the Follow-up with Serum Free Light Chain After Autologous Stem Cell Transplantation in Multiple Myeloma Patients with Measurable M-Protein.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4878-4878
Author(s):  
Byeong Seok Sohn ◽  
Eun Kyoung Kim ◽  
Dok Hyun Yoon ◽  
Myoung Joo Kang ◽  
Dae Ro Choi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Response Assessment ◽  
M Protein ◽  
Response Criteria ◽  
Absolute Increase ◽  
Serum Free Light Chain ◽  
Measurable Disease ◽  
Transplant Registry

Abstract Abstract 4878 Introduction According to international uniform response criteria for multiple myeloma suggested in 2006, the response assessment for patients with oligo- and non-secretory multiple myeloma (MM) can be evaluated by the serum free light chain (FLC) assay. Although the FLC response criteria are not applicable in MM patients with measurable disease, there were several reports suggesting that serial measurement of serum FLC may detect relapse earlier than protein electrophoresis studies. We, therefore, investigated the preceding changes in serial serum FLC assay until progressive disease was confirmed by the international uniform response criteria in post-ASCT patients with measurable disease. Patients and Method We included patients from the AMC MM transplant registry, who met the following (1) undertook ASCT for measurable disease (2) showed, at least, two serial response assessment of stable disease or complete response before progression or relapse by serum or urine M-protein, (3) had periodic serum FLC assay simultaneously tested with serum and/or urine protein electrophoresis at each response assessment. Progressive disease (PD) was defined by increase of ≥ 25% from baseline in serum M-protein (the absolute increase must be ≥ 0.5mg/dL) and/or urine M-component (the absolute increase must be ' 200mg/24h) according to international uniform response criteria. In this investigation, significant increase in the difference between involved and uninvolved FLC (dFLC) and in the involved FLC (iFLC) was defined by increase of ≥ 25% from baseline. The positive predictive value of three cutoff levels for absolute increase, 10mg/L, 20mg/L, 100mg/L, were evaluated for both dFLC and iFLC provided serum FLC ratio was abnormal. Each patient was followed up with 1-3 month intervals according to the protocol for MM patients after ASCT. Result A total 29 patients of 138 patients in the AMC MM transplant registry satisfied above criteria. When the cut-off level for absolute increase was defined as 100mg/L, the significant increase of iFLC in 12 patients (41%) and dFLC in 11 patients (38%) preceded or accompanied with the time of progressive disease observed by M-protein. The median value of preceding time was 2 month (range -5 - 0). When the cut-off level was defined as 20mg/L, the sustained significant increase of iFLC in 21 patients (72%) and dFLC in 17 patients (59%) preceded or accompanied with the time of progressive disease with median of 2 month (range -9 - 0) and 2 month (range, -5 – 0), respectively. At the cut-off level of 10mg/L, the sustained significant increase of iFLC in 23 patients (79%) and dFLC in 21 patients (72%) preceded or accompanied with the time of progressive disease observed by M-protein. The median of preceding time was 2 month (range -11 - 0) and 1 month (range, -11 - 0), respectively. Twenty-eight dFLC values were observed as negative values out of a total 123 data from 29 patients. Of these values, 12 were below normal iFLC concentration, 14 within normal range of iFLC (kappa 8.5 - 23.7 mg/L, lambda 9.5 - 23.5 mg/L), and 2 above normal iFLC concentration. Conclusion In this study, about 70% of patients showed sustained significant increase of iFLC that preceded or accompanied the time of progressive disease observed by M-protein by a median of 2 months at a cut-off absolute increase of 20mg/L. Although there is a subtle difference in prediction rates according to defined cut-off levels, serial follow up of iFLC and sustained increase by 25% during follow-up seems to have a utility in the prediction of progression after ASCT. In addition, interpretations of dFLC may be difficult as it is frequently observed as negative value in post-ASCT MM patients. Therefore, the serial and sustained increase of iFLC may be useful in lower iFLC concentrations. However, there should be more validation with large patients' population. Disclosures No relevant conflicts of interest to declare.

SWOG S0120 Observational Trial for MGUS and Asymptomatic Multiple Myeloma (AMM): Imaging Predictors of Progression for Patients Treated At UAMS,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3955-3955
Author(s):  
Christoph Heuck ◽  
Rachael Sexton ◽  
Madhav Dhodapkar ◽  
Qing Zhang ◽  
Saad Usmani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Research Funding ◽  
Cox Regression ◽  
Time Dependent ◽  
M Protein ◽  
Risk Scores ◽  
Imaging Studies ◽  
Focal Lesions ◽  
Pet Ct

Abstract Abstract 3955 Background: MGUS counts for the majority of monoclonal gammopathies and can be found in approximately 3% of adults older than 50 years. MGUS progresses to active Multiple Myeloma (MM) at a rate of 1–2% per year, thus imparting an average risk of 25% for progression (PRO) over a lifetime once diagnosed. Unfortunately no single laboratory, molecular or imaging variable can reliably predict PRO. S0120 accrued 363 patients at 69 sites across the US between January 1, 2004 and November 1, 2011, of whom 166 had MGUS and 190 AMM, defined according to IMWG criteria, on whom laboratory, gene expression and imaging studies were collected in a prospective fashion. Here we report the results of imaging studies as predictors of progression. Methods: 262 patients with evaluable follow-up were enrolled at the University of Arkansas for Medical Sciences (UAMS) site. MRI and PET-CT studies were performed at baseline and serially thereafter until PRO to symptomatic MM defined by standard variables of M-protein, bone marrow findings and CRAB criteria, according to protocol. Lab studies were performed at three months, six months and one year after registration, then every 12 months for a total of 5 years from registration as well as within 14 days of decision to discontinue observation or within 14 days of progression. MRI parameters included the number of focal lesions (FL) recognized by short TI inversion recovery (STIR) analysis of the axial bone marrow along with an account of bone marrow background intensity compared to adjacent muscles (hypo-, iso-, hyper-intense). PET-CT parameters included number of FDG-avid focal lesions (PET-FL), SUVmax of PET-FL, presence of extra-medullary disease (EMD) as well as the FDG avidity score at L5 (SUV-L5). Evaluable baseline MRI and PET studies were available for 235 and 224 patients, respectively. Results: In the 262 eligible patients enrolled and followed at UAMS, the two subgroups of MGUS and AMM differed by definition in M-protein and bone marrow plasmacytosis; in addition, IgA subclass and Hyperdiploidy molecular subgroup were overrepresented in the AMM group. Patients in the AMM group also had higher risk scores defined by the GEP 70-gene risk model (GEP70). At 24 months from study entry, 18.8% of all patients had progressed to MM (25.6% of AMM patients and 8.2% of MGUS patients) and 11.5% had begun MM therapy (15.8% of AMM patients and 4.5% of MGUS patients). Univariate Cox regression strongly indicated that age ≥ 65, serum albumin <3.5g/dL, B2M >+3.5mg/L, detection of any cytogenetic abnormalities (CA), and suppression of uninvolved light chains were adversely associated with time to PRO. The AMM-constituting features, bone marrow plasmacytosis >10%, M-protein >30g/L, and abnormal K/L ratio also conferred greater hazard of PRO. Risk scores > −0.26 and >1.5 for GEP70 and GEP80, respectively, as well as detection of focal lesions by MRI at baseline carried an elevated HR for PRO. A multivariate Cox regression showed only elevated M-protein, abnormal K/L ratio and GEP70 risk scores > =0.26 to be strongly associated with time to PRO. In the context of this MV model, disease subtype (AMM v MGUS) was insignificant. Inclusion of development of MRI-FL or and PET-FL as time-dependent variables showed that they were associated with time to PRO with HRs of 27.12 and 32.18 respectively. Abnormal K/L ratio and elevated M-protein were lost in this MV model. Analyzing variables linked to initiation of MM therapy, abnormal K/L ratio, elevated BM plasmacytosis, elevated M-protein, GEP70 risk scores >-0.26 as well as detection of MRI-FL at baseline (≥1 FL: HR=4.90; ≥3FL: HR=10.00) were univariately significant. On multivariate analysis, abnormal K/L ratio, elevated M-protein and GEP70 risk scores > – 0.26 were associated with time to treatment for MM. Inclusion of development of MRI-FL or PET-FL as a time dependent variable were associated with time to treatment with HRs of 29.12 and 36.50 respectively. Conclusion: To our knowledge, this is the first comprehensive effort that has used available imaging modalities along with established laboratory and pathology investigations in an attempt to distinguish features predictive of PRO from MGUS to active MM. In addition to the established “high-risk” MGUS/AMM features, we found that presence of MRI-FL at baseline, presence of CA and GEP70 scores >-0.26 carry a higher risk of PRO. Disclosures: Shaughnessy: Myeloma Health, Celgene, Genzyme, Novartis: Consultancy, Employment, Equity Ownership, Honoraria, Patents & Royalties. Barlogie:Celgene: Consultancy, Honoraria, Research Funding; IMF: Consultancy, Honoraria; MMRF: Consultancy; Millennium: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy; Novartis: Research Funding; NCI: Research Funding; Johnson & Johnson: Research Funding; Centocor: Research Funding; Onyx: Research Funding; Icon: Research Funding.

Utility of Interim and Post-Therapy PET/CT in T-Cell and NK-Cell Lymphoma: A Single Institutional Analysis over 9 Years

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3915-3915
Author(s):  
Kota Fukumoto ◽  
Manabu Fujisawa ◽  
Yasuhito Suehara ◽  
Yoshiaki Usui ◽  
Kentaro Narita ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Index Lesion ◽  
Pet Ct ◽  
Post Therapy ◽  
Initial Staging

Abstract Introduction: Positron emission tomography combined with computed tomography (PET-CT) is functional imaging test and has been widely used in malignant lymphoma (ML) for initial staging and monitoring response to treatment. Interim PET-CT (iPET) and post-therapy PET-CT (ePET) is also used to assess the early response and guide subsequent treatment, although its role is still controversial other than in Hodgkin's disease and diffuse large B cell lymphoma. Peripheral T cell lymphoma (PTCL) and natural killer (NK) cell lymphomas are relatively rare and heterogeneous types of ML. The prognosis of T and NK (T/NK) cell lymphoma is poor and no standard treatment is available. Therefore, there is a need to find better prognostic factors or tools for these patients. PET-CT is both sensitive and specific for initial staging of T/NK cell lymphoma, although there have been few studies using i- and ePET in these lymphomas. We investigated the prognostic value of i- and ePET in T/NK cell lymphoma in a retrospective single-center study. Methods: Between June 2006 and June 2015, 79 patients with T/NK cell lymphomas had iPET after 2 to 4 courses of treatment and at the end of treatment at Kameda Medical Center, Japan. iPET was performed just before the next cycle of treatment. Treatment responses were scored according to the Deauville score using a 5-point scale (DS). We defined DS scores 1 - 3 as complete metabolic response (CMR). Standardized uptake value (SUV) measurement was normalized relative to the injected dose and lean body mass. The SUV was measured for all lesions and the highest value for each scan was recorded as maximum SUV (SUVmax). These lesions were identified as indicator lesions. For mid- and end-treatment scans, we recorded the change in SUVmax (DSUV), comparing the index lesion and the highest SUVmax in the scan regardless of the index lesion. Differences in overall survival (OS) and progression-free survival (PFS) were calculated by two-sided log-rank test. PET-CT status was assessed for its ability to predict PFS and OS. Results: The study population consisted of 48 men and 31 women with a median age of 70 years. The most frequent lymphoma diagnoses were peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) (n  = 29), angioimmunoblastic T cell lymphoma (AITL) (n  = 21), anaplastic large cell lymphoma (ALCL) (n  = 6), adult T cell leukemia/lymphoma (ATLL) (n  = 12), enteropathy-associated T cell lymphoma (EATL) (n  = 2), and NK/T cell lymphoma (NKTCL) (n  = 9). Most patients except for ATLL and NK cell lymphoma were instituted with the CHOP-like regimen. Baseline PET scan was positive in all cases and median SUVmax was 13.7 (range, 2.6 - 37.4). iPET results were negative in 17 cases (26%), and ePET results were negative in 22 of 46 (48%) cases. With a median follow up of 30 months, 5-year PFS rate was 66% for obtaining CMR vs. 9.2% for not obtaining CMR (P  < 0.001). The percentages of patients that obtained CMR were 48% (14/29), 62% (13/21), 67% (4/6), 33% (3/9), 50% (1/2), and 56% (5/9) for those with PTCL-NOS, AITL, ALCL, ATLL, EATL, and NKTCL, respectively. The patients who obtained CMR showed significantly longer PFS and OS compared to those who did not. We also analyzed DSUVmax. Using the ROC curve, DSUVmax values between baseline and iPET of > 62% and > 85% were predictive of better PFS and OS (sensitivity 96%, specificity 67%, area under the curve (AUC) 0.89, 95% confidence interval (CI) = 0.82 - 0.97 and sensitivity 49%, specificity 97%, AUC 0.80, 95% CI = 0.70 - 0.90, respectively). We examined the positive and negative predictive values (PPV and NPV) and accuracy in predicting PFS and OS in 66 patients who underwent iPET. Of 35 iPET-positive patients, 31 (89%) showed progression, and 26 (74%) died during the follow-up. On multivariate Cox regression analysis, obtaining CMR at iPET emerged as an independent prognostic factor for PFS and OS (P<0.001 and P<0.001, respectively). Conclusions: Our data suggest that patients with positive results on i- or ePET should be considered candidates for intensive therapeutic strategies to improve their clinical outcome. Large prospective studies of patients with tumors of a homogeneous histological subtype within the T/NK cell lymphoma, treated with a uniform protocol, and evaluated on the basis of standardized criteria are warranted. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Continued monoclonal protein response beyond day 100 after auto-transplantation for multiple myeloma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8587-8587
Author(s):  
Wilson I. Gonsalves ◽  
Morie Gertz ◽  
Yi Lin ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Response ◽  
M Protein ◽  
Disease Assessment ◽  
Maximal Response ◽  
Solitary Plasmacytoma ◽  
Bone Marrow Plasma ◽  
Smoldering Myeloma ◽  
Protein Response

8587 Background: Patients (pts) undergoing an auto-transplant (ASCT) for multiple myeloma (MM) have disease assessment approximately 100 days later. This result may direct decisions of further therapy versus observation. However, some pts continue to experience a decline in their serum or urine monoclonal (M) - protein after day 100 without more therapy. Little is known about the prevalence and significance of this phenomenon. Methods: We identified 903 MM pts who underwent ASCT within 12 months (mos) of diagnosis (Dx) at our institution. Their day 100 post-ASCT M-protein from serum and urine electrophoresis with immunofixation as well as serum free light chains were compared to subsequent values during follow-up. The IMWG criteria were used to evaluate response. Results: Of the pts included, 510 (56%) were male and median age at ASCT was 59 (range 28-76). Median follow up from Dx and ASCT was 82 mos (95% CI; 75 - 86) and 74 mos (95% CI; 70 - 79) respectively. There were 453 (50%) pts seen in follow-up who had not achieved a CR at Day 100 nor initiated on maintenance therapy. Of these pts, 167 (37%) had a further decrease in their M-protein after day 100 at a median of 9.4 mos (95% CI; 8 – 10) post-ASCT. Given the time taken for maximal response, we assessed patients’ clinical response at one year post-ASCT. Compared to patients who did not have further clinical response between day 100 and 1 year, pts experiencing further response had a longer time to next therapy (TTNT) (43 mos vs. 17 mos, P < 0.001) as well as overall survival (OS) (96 mos vs. 62 mos, P < 0.001). Positive predictors for continued response included having an IgG isotype, evolution from a pre-existing MGUS, smoldering myeloma or solitary plasmacytoma and a Day 100 bone marrow plasma cell < 3%. In a multivariate analysis, elevated creatinine at Dx and lack of continued response predicted for shorter TTNT and OS post-ASCT. Older age and high-risk MM by FISH also predicted a shorter OS. Conclusions: In MM pts undergoing ASCT, continued M - protein response was seen in a third of the pts lacking a CR at day 100. This phenomenon appears prognostic and must be considered when interpreting studies evaluating post-ASCT response and the need for further therapy.

scholarly journals Tracking Daratumumab Clearance Using Mass Spectrometric Approaches: Implications on M Protein Monitoring and Reusing Daratumumab

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2707-2707
Author(s):  
Nadine Abdallah ◽  
David L Murray ◽  
Angela Dispenzieri ◽  
Prashant Kapoor ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Plasma Cell ◽  
Research Funding ◽  
Univariate Analysis ◽  
M Protein ◽  
Urine Protein ◽  
Advisory Committees ◽  
Plasma Cell Disorders

Abstract Background: MASS-FIX is a screening method for serum and urine monoclonal proteins in multiple myeloma and related plasma cell disorders, which uses immunoglobulin enrichment coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MALDI-TOF). In addition to superior sensitivity over conventional gel-based techniques, MASS-FIX can distinguish therapeutic monoclonal antibodies (MoAb) from patient's M protein. As the utilization of therapeutic MoAbs increases, it is essential to understand the persistence pattern of these therapeutic antibodies in the serum. We designed this study to evaluate the duration of daratumumab detection by MASS-FIX in the serum of treated patients. Methods: We used a prospectively maintained database at Mayo clinic to identify patients with multiple myeloma and related plasma cell disorders who were treated with a daratumumab-containing regimen anytime during their disease course and had serial MASS-FIX data available after discontinuation of daratumumab. A univariate analysis was performed to assess for factors that may impact the clearance of daratumumab. Results: We included 125 patients with plasma cell disorders who received daratumumab as first or subsequent line of treatment between March 15 th, 2016, and March 4 th, 2020. The median age was 60.2 years and 57% were male. The most common diagnoses were multiple myeloma (70%) and light chain amyloidosis (18%). Daratumumab-based treatments were initiated after a median of 28.8 (IQR: 6.4-76.3) months from initial diagnosis. The most common regimen used was daratumumab, bortezomib and dexamethasone (23%); 26% underwent transplant after daratumumab-based induction. The median duration of treatment with a daratumumab-based regimen was 208 (IQR: 99-479) days. The median follow-up from the time of daratumumab discontinuation was 457 (95% CI: 346-NR) days. By last follow up, daratumumab was not detected by MASS-FIX in 93 (74%) patients but remained detectable in 32 (26%) patients. The median time from daratumumab discontinuation to disappearance of daratumumab by MASS-FIX was 160 (IQR: 107-233) days. On univariate analysis, the presence of ≥0.5 grams of urine protein was associated with earlier disappearance of daratumumab on MASS-FIX [risk ratio (RR): 2.0, P=0.02). The median time from daratumumab discontinuation to disappearance of daratumumab on MASS-FIX was 116 (95%CI: 76-160) days in patients with urine protein ≥0.5 grams and 203 (95%CI: 162-216) days in patients with urine protein &lt;0.5 grams (P=0.02). There was no association between the time to disappearance of daratumumab by MASS-FIX and old age ≥70 (RR: 0.9, P=0.81], male gender (RR: 0.9, P=0.60), eGFR &lt;60 (RR: 1.0, P=0.98), daratumumab schedule (every 1/2 weeks vs &gt;2weeks) (RR: 1.0, P=0.97), treatment duration (&lt;200 days vs ≥200 days) ( RR: 1.0, P=0.95), or transplantation status (RR: 1.0, P=0.98). Conclusion: The therapeutic monoclonal antibody daratumumab remains detectable in the serum of treated patients by MASS-FIX for several months after discontinuation and the duration varies between individual patients. This data has implications for diagnostic and monitoring testing and may provide guidance for reuse of daratumumab in clinical trials and practice. Proteinuria is associated with earlier disappearance of daratumumab by MASS-FIX and may have implications in patients with amyloidosis and monoclonal immunoglobulin deposition disease (MIDD). Further studies are needed to identify additional factors associated with the timing of disappearance. Disclosures Murray: Mayo Clinic: Other: Has received patents for the Mass-Fix technology which has been licensed to the Binding Site with potential royalties.. Dispenzieri: Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding. Kapoor: Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Gertz: Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Ionis Pharmaceuticals: Other: Advisory Board; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring. Dingli: Alexion: Consultancy; Novartis: Research Funding; Apellis: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; GSK: Consultancy. Kumar: Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Roche-Genentech: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Oncopeptides: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Carsgen: Research Funding; Tenebio: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

scholarly journals Comparison of Assesment of Imaging Response with Magnetic Resonance (MR) and 18fdg-PET/TC in Multiple Myeloma (MM). Single Centre Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5707-5707
Author(s):  
Adrian Alegre ◽  
Beatriz Aguado ◽  
Miriam González-Pardo ◽  
Evelyn Acuña ◽  
Álvaro Arriero ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Magnetic Resonance ◽  
Bone Involvement ◽  
Whole Body ◽  
Advisory Committees ◽  
Leptomeningeal Involvement ◽  
18Fdg Pet ◽  
Pet Ct

Abstract Introduction: Conventional radiography remains the “gold standard” technique for bone involvement assessment in patients with multiple myeloma (MM). Newer imaging modalities such as whole-body Magnetic Resonance (MR) and 18FDG-PET/CT have emerged as more sensitive techniques than routine skeletal survey in the detection of bone involvement in the diagnostic and follow up of patients with MM. The advantages and disadvantages of MR and 18FDG-PET/CT are discussed. Patients and methods: We have retrospectively analyzed 12 patients since 2012 to 2014 with multiple myeloma in our institution whose bone involvement was evaluated with MR and 18FDG-PET/CT. Age range: 36-70. Seven patients were female and five were male. Eight cases were treated with an induction regimen containing bortezomib, three cases with chemotherapy with alternating VBCMP/VBAD and one of them with VAD. After induction, ten of them received autologous stem cell transplantation (ASCT), one patient allogeneic stem cell transplantation and one patient no transplantation. Results: All patients presented bone lesions on MR and all of them were also positive at PET/CT. One showed leptomeningeal involvement on RM and PET. Regarding extramedullar disease two patients presented soft tissue masses and in other two cases there was ganglionar involvement, all of them positives by both techniques. Of nine evaluable patients after complete treatment, six of them have a negative PET and three have a low positive SUV value, however eight of them still had persistent residual lesions on MR, what could indicate not stringent complete response. The patient with leptomeningeal involvement had both MR and PET negative result after treatment. Comments and conclusions: Our data suggest that whole-body MR and 18FDG-PET/CT provide valuable complementary information, MR could be superior to assess extent of lesions and PET to monitor disease activity and to detect asymptomatic relapse. The optimal imaging technique for the management of patients with MM is not well defined and our proposal is a multimodality imaging approach according to individualized criteria. References: Caers J et al. The role of positron emission tomography-computed and magnetic resonance imaging in diagnosis and follow-up of multiple myeloma. Haematologica 2014;99(4):629-637. doi:10.3324/haematol.2013.091918. Agarwal A et al. Evolving Role of FDG PET/CT in Multiple Myeloma Imaging and Management. AJR 2013;200:884-890. Dimopoulos D et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia 2009, 1–12. doi:10.1038/leu.2009.89 Disclosures Alegre: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3396-3396 ◽  
Author(s):  
Robert Kyle ◽  
Ellen Remstein ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Paul Kurtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
M Protein ◽  
Cell Content ◽  
Bone Marrow Plasma ◽  
M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were &gt; 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein &lt; 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells &lt; 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p &lt; 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p &lt; 0.001) and reduction of uninvolved immunoglobulins (p &lt; 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

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