Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3

Usmani, Saad Z.; Mitchell, Alan; Waheed, Sarah; Crowley, John; Hoering, Antje; Petty, Nathan; Brown, Tracy L.; Bartel, Twyla; Anaissie, Elias; Rhee, Frits van; Barlogie, Bart

doi:10.1182/blood-2012-08-451690

Cited by 189 publications

(140 citation statements)

References 14 publications

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“…In particular, a SUV max value >4.2 retained independent prognostic relevance in multivariate regression analyses along with the presence of ISS stage 3 and failure to achieve CR during or after first-line treatment. Although other studies previously showed the prognostic value of FDG PET/CT at baseline in patients receiving novel agents plus ASCT (1,2,17), to the best of our knowledge, this is the first report providing demonstration that PET/CT involvement predicts outcomes also in elderly patients treated with novel agents and chemotherapy. Several factors related to the myeloma cell burden and/or reflecting the biologic characteristics of the disease at the time of diagnosis have a well-defined prognostic role in multiple myeloma patients.…”

Section: Discussionmentioning

confidence: 83%

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma

Zamagni¹,

Nanni

Mancuso³

et al. 2015

Clinical Cancer Research

150

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Purpose: To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012.Experimental Design: All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months.Results: Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUV max was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUV max >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/ CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUV max >4.2 following first-line treatment was independently associated with exclusive PET/CT progression.Conclusions: PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression.

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Section: Discussionmentioning

confidence: 83%

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma

Zamagni¹,

Nanni

Mancuso³

et al. 2015

Clinical Cancer Research

150

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“…Studying 277 patients with a GEP-derived risk information (out of a higher group of 302 patients) with newly diagnosed MM undergoing ''Total Therapy 3 Trial'' (2 cycles of VTD-PACE: bortezomib, thalidomide, dexamethasone and 4-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, etoposide), it was shown that [3 focal lesions on day 7 FDG PET/CT resulted in inferior overall survival and progression-free survival [48,49]. This should suggest the opportunity of changing therapy in the subset of patients exhibiting [3 FDG-uptaking focal lesions on day 7 of induction therapy, especially in those with high-risk MM as defined by GEP [49].…”

Section: Response To Therapy and Prognostic Evaluation In Overt MMmentioning

confidence: 99%

18F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders

et al. 2014

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Conventional radiographic skeletal survey has been for many years the gold standard to detect the occurrence of osteolytic lesions in patients with multiple myeloma (MM). However, the introduction of more sensitive imaging procedures has resulted in an updated anatomic and functional Durie and Salmon "plus" staging system and has remarkably changed the diagnostic and prognostic approach to this tumor. It is now established that (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) combined with low-dose computed tomography (CT), shortly designated PET/CT, exhibits a higher screening and diagnostic sensitivity and specificity over the skeleton X-ray. In patients with monoclonal gammopathy of undetermined significance and in those with smoldering MM, PET/CT is consistently unable to detect focal and/or diffuse marrow abnormalities. Conversely, based on a systematic review of 18 studies comprising almost 800 MM patients, PET/CT was able to detect MM osteolytic lesions with a sensitivity of approximately 80-90% and a specificity of 80-100%. Importantly, a poor degree of concordance has also been emphasized between PET/CT and whole-body magnetic resonance imaging (WB-MRI) in that when both techniques were applied to the same patients, double-positive results were recorded in approximately 30% of the cases, but in the majority of them, a higher number of lesions were revealed with PET/CT than with MRI. Double-negative results, on the other hand, were found in about 22% of the patients. Because PET/CT is able to identify tumor foci throughout the body, it can be usefully applied to the study of solitary bone plasmacytoma and extra-medullary plasmacytoma: In both conditions, the detection of additional, previously overlooked sites of skeletal involvement would falsify the diagnosis of single-district disease, upstage the tumor, and therefore require a different therapeutic approach. In addition, although PET/CT is poorly sensitive to diffuse bone marrow infiltration, it can anticipate a site of impending fracture throughout the body and can discriminate old from new pathologic fractures. MRI should, however, be preferred when vertebral bodies are suspected to be involved and the risk of vertebral fracture is to be assessed. PET/CT is a sensitive and reliable procedure to evaluate the response to chemotherapy and/or radiotherapy, which is shown by a remarkable reduction and sometimes total disappearance of FDG accumulation in the involved bony structures, although these structures remain morphologically abnormal. Conversely, an increased focal uptake of FDG in apparent remission patients often precedes clinically overt relapse. PET/CT should be preferred to other imaging techniques to assess the remission status after autologous stem cell transplantation. In patients with primary and remission-induced non-secretory MM, the use of PET/CT may help to early detect single or multiple districts of focal non-secretory relapse. Osteonecrosis of the jaw, its location, and extent in MM patients receiving b...

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“…The Bologna group demonstrated that patients with newly diagnosed MM who presented with more than 3 FLs, a high standardized uptake value (SUV), and extramedullary disease (EMD) on diagnostic PET/CT had a poor PFS [6]. PET-CT has been an useful tool not only for staging at diagnosis, but also for monitoring the response after treatment, as demonstrated by some studies mainly conducted on patients undergoing auto-SCT [8,9].…”

Section: Introductionmentioning

confidence: 99%

The Role of Positron Emission Tomography with 18F-Fluorodeoxyglucose Integrated with Computed Tomography in the Evaluation of Patients with Multiple Myeloma Undergoing Allogeneic Stem Cell Transplantation

Patriarca

Carobolante

Zamagni

et al. 2015

Biology of Blood and Marrow Transplantation

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Positron emission tomography (PET) integrated with computed tomography (PET/CT) has been reported to be useful for screening myelomatous lesions at diagnosis in patients with multiple myeloma (MM) and for monitoring response to autologous stem cell transplantation (auto-SCT). The aim of the study was to evaluate the prognostic significance of PET/CT in MM patients who received allogeneic stem cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed by allo-SCT, either as consolidation or salvage treatment, were studied with PET/CT before and/or within 6 months after allo-SCT. The number, the maximum standard uptake value (SUV), and the location (medullary or extramedullary) of focal lesions (FLs) were recorded and investigated as predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22 patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs, and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3 FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was present in 6 patients (11%). Multivariate analysis of prognostic factors before allo-SCT showed that persistence of EMD at transplantation was an independent predictor of poor PFS, whereas OS was negatively influenced by unrelated donor and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo-SCT. Multivariate analysis of post-treatment variables showed that persistence of EMD and failure to obtain complete response or very good partial response after allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23 patients who maintained or reached a PET complete remission showed a significantly prolonged PFS and OS compared with the 23 patients with persistence of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus 47%, P = .001). This study indicates that PET/CT imaging before and after allo-SCT is significantly associated with the outcome, suggesting the utility of this technique for MM staging before allo-SCT and for response monitoring after the transplantation.

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Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3

Abstract: Key Points Presence of more than 3 PET focal lesions after day 7 first cycle of induction chemotherapy can predict for inferior overall survival and progression free survival.

Cited by 189 publications

References 14 publications

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma

18F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders

The Role of Positron Emission Tomography with 18F-Fluorodeoxyglucose Integrated with Computed Tomography in the Evaluation of Patients with Multiple Myeloma Undergoing Allogeneic Stem Cell Transplantation

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