Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 992-992

Abstract: F-18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) enables to detect with relatively high sensitivity and specificity myeloma bone disease and extramedullary sites of metabolically active clonal plasma cells. FDG-PET/CT has also been used to assess and monitor the metabolic response to therapy and to predict the prognosis. One of the major limitation of PET/CT is the lack of standardized image criteria and of inter-observer reproducibility in interpreting the results. Aim of the present sub-study was to prospectively evaluate FDG-PET/CT at diagnosis, after 4 cycles of induction therapy and prior to maintenance therapy in a sub-group of patients enrolled into EMN02/HO95 MM international phase III trial. In particular, the two primary end-points were firstly to assess the prognostic significance of PET/CT at diagnosis and after therapy and secondly to standardize PET/CT evaluation by centralized imaging and revision and definition of criteria for interpretation. Seven hundred and 18 patients with newly diagnosed transplant-eligible symptomatic MM have been prospectively randomized in Italy from February 2011 through April 2014 to receive 4 cycles of bortezomib-melphalan-prednisone (VMP) vs high-dose melphalan and single or double autologous stem cell transplantation (ASCT) as intensification following induction with bortezomib-cyclophosphamide-dexamethasone (VCD). Consolidation therapy with bortezomib-lenalidomide-dexamethasone vs no consolidation was planned after VMP or ASCT(s), followed by lenalidomide maintenance until progression or toxicity. One hundred and three patients were included in the PET/CT imaging sub-study, and followed for a median of 24 months. By study design, PET/CT was performed and analysed in each of the 8 participating centres at baseline, after induction therapy and prior to the start of maintenance (EOT). Each PET scan was a posteriori re-interpreted in a blinded independent central review process, managed by WIDEN®, by a panel of 5 expert nuclear medicine physicians. They described the following characteristics: bone marrow metabolic state (BM), number (Fx) and score (Fs) of focal PET positive lesions, osteolysis (Lx), presence and site of extramedullary disease (EM), and fractures(Fr), according to the IMPeTUs criteria (Nanni et al, EJNM 2015). Moreover, a global score (GS), from 1 to 5, was given to each patient, considering the highest score among BM, Fx, Fs and EM. Concordance among reviewers on different metrics was calculated using Krippendorf's alpha (AK) coefficient Baseline characteristics of the patients were the following: median age 58 years, ISS and R-ISS stage III 15% and 10%, high-risk cytogenetics (t(4;14) ± del(17p) ±del (1p)±1q gain detected by FISH) 42%. At baseline, 78% of the patients had FLs, with a median SUVmax of 6.0. The percentages of PET positive patients for the different characteristics are summarized in table 1. The agreement among reviewer was good for BM (AK=0.49), Fx (AK=0.65), Fs (AK=0.62), Lx (AK=0.62) and EM (AK=0.40). Of all parameters, only Fx ≥ 4 was associated with worse PFS and OS (P = 0.06) Following 4 cycles of VCD, PET/CT remained positive in 59% of the patients, with a median SUVmax of 3.7. Of all parameters, only Fs ≥ 4 was predictive of worse OS (P= 0.05). Prior to maintenance therapy, PET/CT remained positive in 34% of the patients, with a median SUVmax of 3.4. Normal PET/CT findings before maintenance (66%) were associated with a significant improvement in PFS, in particular the following: presence of FLs (P=0.03), Fx ≥ 4 (P=0.001), Fs ≥2 (P=0.03), 3 (P=0.03) and 4 (P=0.006) and SUVmax ≥ 3.4 (p=0.002). GS was also predictive for PFS if ≥ 3 (P=0.033), 4 (P=0.0001) and 5 (P=0.004). The same parameters were also predictive for OS. The prognostic relevance of pre-maintenance PET/CT was retained across the randomization arm (VMP or ASCT), in terms of PFS and OS. In conclusion, PET/CT was confirmed to be a reliable predictor of outcome in newly diagnosed transplant eligible MM patients, whatever the treatment. Normalization of PET/CT before maintenance was associated with a significant improvement for PFS and OS. FDG-PET/CT is by now the preferred imaging technique for evaluating and monitoring response to therapy. Acknowledgments: this study was partially supported by a grant to Elena Zamagni from Fondazione del Monte di Bologna e Ravenna Table 1 Table 1. Disclosures Gay: Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees. Larocca:Bristol-Myers Squibb: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Sonneveld:Celgene: Other: Advisory board, Research Funding; Onyx: Other: Advisory board, Research Funding; Millennium: Other: Advisory board, Research Funding; Janssen-Cilag: Other: Advisory board, Research Funding. Cavo:Amgen: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.992.992

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 39, No. 4 ( 2012-4), p. 569-580

Type of Medium: Online Resource

ISSN: 1619-7070 , 1619-7089

URL: Article

DOI: 10.1007/s00259-011-2031-6

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2012

detail.hit.zdb_id: 2098375-X

In: eClinicalMedicine, Elsevier BV, Vol. 60 ( 2023-06), p. 102017-

Type of Medium: Online Resource

ISSN: 2589-5370

URL: Article

DOI: 10.1016/j.eclinm.2023.102017

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2946413-4

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 257-257

Abstract: F-18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) is actually considered as the standard technique to assess and monitor the metabolic response to therapy and to define minimal residual disease (MRD) status outside the bone marrow (BM) in multiple myeloma (MM) patients. In this regard, standardization of image criteria and definition of cut-offs for positivity/negativity is of highly importance. Aim of the present study was to prospectively evaluate FDG-PET/CT at diagnosis and prior to maintenance therapy in a joined analysis of a sub-group of patients with newly diagnosed transplant-eligible MM, enrolled in 2 independent European randomized phase III trials (EMN02/HO95 and IFM2009) (Cavo M et al, Blood 2017 abs; Attal M et al, NEJM 2017). The primary end-point was to standardize PET/CT evaluation by centralized imaging and revision and to define criteria for PET negativity after therapy (MRD definition). 236 patients (102 and 134 from the EMN02 and IFM2009 trial, respectively) were enrolled in the PET/CT imaging sub-studies and followed for a median of 62.9 (IQR: 44.9-67.9) months. By study design, PET/CT scans were performed locally at baseline (B) and prior to the start of maintenance (PM), uploaded in a central website and re-interpreted a-posteriori in a blinded independent central review process, by a panel of expert nuclear medicine physicians. According to the IMPeTUs criteria (Nanni C et al, EJNM 2017), the five-point Deauville scores (between 1 and 5) were applied to the following parameters: bone marrow (BM), focal lesions (FLs), extramedullary disease (EMD). The impact of each parameter on outcomes was evaluated by landmark analyses at PM; the univariate and multivariate analyses were stratified by trial to smooth out differences between the 2 studies. Baseline characteristics of the patients were generally homogeneous between the 2 trials and as follows: median age 59 years, ISS and R-ISS stage III 15.8% and 11.5%, respectively, high-risk cytogenetics (t(4;14) ± del(17p) ± t(14;16) detected by FISH) 14%. Fifty seven percent of the patients were randomized in the transplant arm, and 43% in the bortezomib-intensification arm, with a higher percentage in the IFM2009 vs EMN02 trial (54% vs 24%, respectively). At baseline, 80% of the patients had FLs, with a median maximum standardized uptake value (SUVmax) of 5. Median BM SUVmax was 3. Both median FLs and BM SUVmax were slightly higher in the IFM2009 vs the EMN02 trial (5.7 vs 4.2 and 3.7 vs 2.68, respectively), while reference SUVmean (mediastinal blood pool and liver) did not differ between the 2 studies. FLs Deauville score (FS) and BM Deauville score (BMS) 〉 3 (higher than the liver) were present in 79.8% and 35.5% of the patients, respectively, with no difference between the 2 trials. EMD was present in 11% of the patients. Prior to maintenance therapy, median FLs and BM SUVmax were 3.6 and 2.3, respectively, with 53.5% and 71.2% of the patients obtaining a FS and BMS ≤ 2 and 79% and 91.4% ≤ 3, respectively. In univariate analysis, at Landmark time prior to maintenance, attaining a FS and BMS ≤ 3 was the strongest predictor for prolonged PFS (FS≤ 3 vs 〉 3: median 40 vs 26.6 months, HR 0.6, CI 0.39-0.98, P= 0.0019; BMS≤ 3 vs 〉 3: median 39.8 vs 26.6 months, HR 0.47, CI 0.24-0.91, P= 0.024, respectively) and OS (FS≤ 3 vs 〉 3: estimate at 63 months 73% vs 63.6% months, HR 0.51, CI 0.26-0.98, P= 0.028; BMS≤ 3 vs 〉 3: estimate at 75.5% vs 49.7%, HR 0.28, CI 0.12-0.64, P= 0.002, respectively) and could be identified as the most representative cut-off values for PET negativity after therapy. Of the two PM scores, only FS ≤ 3 retained prognostic relevance in the subgroup of patients not receiving transplant, in terms of PFS. In Cox multivariable analysis, FS and BMS ≤ 3 at PM were independent predictors of prolonged PFS (FS: HR 0.58, CI 0.35-0.96, P= 0.036; BMS HR 0.41, CI 0.20-0.84, P= 0.014) and OS (FS: HR 0.36, CI 0.17-0.74, P= 0.005; BMS HR 0.24, CI 0.09-0.63, P= 0.004). In conclusion, FDG PET/CT was confirmed to be a reliable predictor of outcomes in newly diagnosed MM, regardless of treatment. Reduction of FDG uptake lower than the liver after therapy, both in the FLs and in the BM (FS and BMS), was an independent predictor for improved PFS and OS. Findings from this analysis could be proposed as standardized criteria to define PET negativity after therapy, confirming the value of Deauville scores in MM. Disclosures Zamagni: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Tacchetti:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Gallamini:Takeda: Consultancy, Speakers Bureau. Patriarca:Jazz: Other: Travel, accommodations, expenses; Medac: Other: Travel, accommodations, expenses; Celgene: Other: Advisory Role; Travel, accommodations, expenses; Janssen: Other: Advisory role; MSD Italy: Other: Advisory Role. Macro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. Boccadoro:Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding. Garderet:Takeda: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Perrot:Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Karlin:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Cavo:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-111321

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Cancers, MDPI AG, Vol. 14, No. 4 ( 2022-02-19), p. 1055-

Abstract: Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F] FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 〉 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.

Type of Medium: Online Resource

ISSN: 2072-6694

URL: Article

DOI: 10.3390/cancers14041055

Language: English

Publisher: MDPI AG

Publication Date: 2022

detail.hit.zdb_id: 2527080-1

In: Clinical and Translational Imaging, Springer Science and Business Media LLC, Vol. 9, No. 5 ( 2021-10), p. 423-438

Type of Medium: Online Resource

ISSN: 2281-5872 , 2281-7565

URL: Article

DOI: 10.1007/s40336-021-00443-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2736976-6

detail.hit.zdb_id: 2712000-4

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4321-4321

Abstract: Background: 18F-FDG-PET/CT is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in multiple myeloma (MM) patients. A joined analysis of two prospective randomized trials in newly diagnosed transplant-eligible MM (NDTEMM) patients applied for the first time the Deauville Scores (DS) to focal lesions (FS) and bone marrow uptake (BMS) and showed the liver background (DS 〈 4) to be the best cut-off to define PET negativity after therapy (Zamagni et al, ASH 2018). Multiparameter Flow cytometry (MFC) at the sensitivity level of 10-5 is one of the standardized methods to assess MRD in the BM (Kumar SK, Lancet Oncol 2016). In this analysis, we aimed at comparing MRD data by PET/TC assessment and MFC in the multicenter phase II randomized FORTE trial for NDTEMM patients. Methods: NDTEMM patients ≤65 years were randomized to receive carfilzomib, lenalidomide, dexamethasone (KRD) induction - autologous stem cell transplantation (ASCT) intensification-KRd consolidation (arm A); KRd12 (arm B) and carfilzomib, cyclophosphamide, dexamethasone (KCd) induction-ASCT intensification-KCd consolidation (arm C). Thereafter, patients were randomized to maintenance with lenalidomide alone or lenalidomide plus carfilzomib. MRD evaluation was performed by 8-color second-generation flow cytometry (sensitivity 10-5) in patients who achieved at least VGPR before maintenance (Gay F, ASCO 2019). PET/CT scans were performed locally at baseline (B) and prior to the start of maintenance (PM) and the DS were applied both in the BM and FLs as previously described. Cramér's V coefficient was used to measure the concordance between PET/TC and MFC; Fisher or X2 tests were adopted, where appropriate, to evaluate the statistical significance, at the level of 0.05. Results: 182 out of the 474 global patients enrolled in the trial had a matched PET/CT and MFC evaluation available and were included in the present analysis. Baseline characteristics of the patients were as follows: median age 57 years, ISS and R-ISS stage III 18% and 10%, respectively, high-risk cytogenetics (t(4;14) ± del(17p) ± t(14;16), detected by FISH) 26%, reflecting baseline clinical features of the entire FORTE population. At B, 92% of the patients had FLs, with a median maximum standardized uptake value (SUVmax) of 5.7 [IQR: 4.1-8.1], 11% presented extra-medullary lesions and nearly all the patients had increased BM uptake, with a median SUVmax of 3.3 [IQR: 2.8-4.3] . FS and BMS ≥4 were present in 87% and 59% of the patients, respectively. A higher FS at B was significantly correlated with ISS stage III (P= 0.04), while higher BMS with lower hemoglobin level (P= 0.002) and higher free light chain ratio (P= 0.004). At PM, PET/TC negativity according to DS 〈 4, was present in 78% in the FLs and 85% in the BM, respectively. No significant correlations between PET/CT negativity after therapy and baseline prognostic factors or PET/CT characteristics were found. 95% and 67.5% of the patients achieved ≥ VGPR and CR as best response, respectively, while 75% of them achieved MFC MRD negativity. The achievement of a best CR significantly correlated with BMS 〈 4 at PM (P= 0.013). We analyzed the concordance between MRD results by the two techniques and Cramér's V coefficient measured a strong association, with a value of 0.76 (p 〈 0.001). In particular, concordance between PET/CT BMS and MFC was 94% (80% both negative, 14% both positive) while 6% were PET/CT negative and MFC positive. FS and MFC were concordant in 63% of the cases (57% both negative, 6% both positive) while 20% were PET/CT negative and MFC positive and 17% showed residual FLs in the context of MFC negativity. The persistence of MFC positivity at PM was significantly related to a higher BMS and SUVmax at the same time-point. Conclusion: In conclusion, the present analysis confirms the applicability and validity of DS criteria for the definition of PET/CT MRD outside the BM in an independent prospective series of NDTEMM patients. PET/CT negativity significantly correlated with the achievement of best CR. PET/CT and MFC at the sensitivity level of 10-5 showed a good concordance in the BM, while were also confirmed to be complementary outside (FLs). Future analyses will show the impact of PET/CT in comparison with BM MRD techniques on patient's outcomes. Disclosures Zamagni: Celgene Corporation: Honoraria, Other: Advisory board, Speakers Bureau; Janssen: Honoraria, Other: Advisory board, Speakers Bureau; Amgen: Honoraria, Other: Advisory board, Speakers Bureau; BMS: Honoraria, Other: Advisory Board, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Sanofi: Honoraria, Other: Advisory Board, Speakers Bureau. Gay:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Omedé:Janssen: Membership on an entity's Board of Directors or advisory committees. Galli:Janssen: Honoraria; Leadiant (Sigma-Tau): Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria. Zambello:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Gamberi:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Patriarca:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Tacchetti:Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria; Oncopeptides: Honoraria, Speakers Bureau; BMS: Honoraria. Boccadoro:Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding. Cavo:bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau. Oliva:Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-125134

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 45, No. 5 ( 2018-5), p. 712-719

Type of Medium: Online Resource

ISSN: 1619-7070 , 1619-7089

URL: Article

DOI: 10.1007/s00259-017-3909-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2018

detail.hit.zdb_id: 2098375-X

In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 43, No. 3 ( 2016-3), p. 414-421

Type of Medium: Online Resource

ISSN: 1619-7070 , 1619-7089

URL: Article

DOI: 10.1007/s00259-015-3200-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 2098375-X

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 27-28

Abstract: Background: 18F-FDG-PET/CT is currently the standard technique to define imaging-minimal residual disease (MRD) in multiple myeloma (MM) patients. A joint analysis of 2 prospective randomized trials in newly diagnosed transplant-eligible MM (NDTEMM) patients applied for the first time the Deauville Scores (DS) to focal lesions (FS) and bone marrow uptake (BMS) showing the liver background (DS & lt; 4) as the best cut-off to define PET/CT negativity after therapy and complete metabolic response (CMR) (Zamagni et al, ASH 2018). Validation of this new standardized criteria in an independent prospective series of NDTEMM patients is highly required. Imaging-PET/CT MRD also showed to be complementary to Multiparameter Flow Cytometry (MFC) in predicting patient's outcomes (Moreau P, JCO 2017). In this analysis, we aimed at confirming the applicability and validity of DS criteria to define PET/CT CMR and showing their impact on patient's outcomes in the multicenter phase II randomized FORTE trial for NDTEMM patients. We also looked at the complementarity with BM techniques, especially MFC. Methods: NDTEMM patients ≤ 65 years were randomized to receive carfilzomib, lenalidomide, dexamethasone (KRD) induction - autologous stem cell transplantation (ASCT) intensification-KRd consolidation (arm A); KRd12 (arm B) and carfilzomib, cyclophosphamide, dexamethasone (KCd) induction-ASCT intensification-KCd consolidation (arm C). Thereafter, patients were randomized to maintenance with lenalidomide alone or plus carfilzomib. PET/CT scans were performed locally at baseline (B) and prior to the start of maintenance (PM). DS were applied both in the BM and FLs, as previously described (Zamagni E, EHA 2020). CMR was defined as DS & lt; 4 both in the FLs and BM. MRD evaluation was performed by 8-color second-generation flow cytometry (sensitivity 10-5) in patients who achieved at least VGPR before maintenance (Gay F, ASCO 2019). The impact of each parameter on outcomes was evaluated by landmark analyses at PM. A multivariable Cox regression analysis was adopted to identify independent predictors for PFS and OS. Results: 182 out of the 474 global patients enrolled in the trial had a pre- and post-treatment PET/CT evaluation available and were included in this analysis. Patients' baseline characteristics were: median age 57 years, ISS and R-ISS stage III 18% and 10%, respectively, high-risk cytogenetics (t(4;14) ± del(17p) ± t(14;16), detected by FISH) 26%, reflecting baseline clinical features of the entire FORTE population. At B, 93% of patients had FLs, with a median maximum standardized uptake value (SUVmax) of 5.7 [IQR: 4.1-8.1], 7% presented extra-medullary lesions and nearly all patients had increased BM uptake, with a media n SUVmax of 3.4 [IQR: 2.8-4.3]. FS and BMS ≥ 4 were present in 87% and 57% of patients, respectively. At PM, PET/CT negativity according to DS & lt; 4, was present in 80% in the FLs and 85% in the BM, respectively. 63% showed CMR. 92% and 61% of patients achieved ≥ VGPR and CR as best response, respectively, while 73% of them achieved MFC MRD negativity. The achievement of a best CR significantly correlated with BMS & lt; 4 at PM (P= 0.003). In univariate analysis, at Landmark time PM, FS & lt;4 significantly influenced both PFS and OS (survival probability at 36 mos 78% vs 68%, HR 0.32, CI 0.15-0.68, P= 0.003; 94% vs 80%, HR 0.28, CI 0.09-0.93, P= 0.038, respectively). Achievement of CMR was a strong predictor for prolonged PFS (survival probability at 36 mos 79% vs 58%, HR 0.38, CI 0.18-0.81, P= 0.012), with a trend on OS (survival probability at 36 mos 92% vs 87%, HR 0.34, CI 0.10-1.22, P= 0.099) (fig.1). Patients achieving both PET/CT CMR and MFC negativity at PM showed significantly extended PFS and OS (survival probability at 36 mos 86% vs 55%, HR 0.21, CI 0.09-0.49, P & lt;0.001; 96% vs 76%, HR 0.17, CI 0.04-0.78, P= 0.023, respectively) compared to all the others (fig.2). In Cox multivariable analysis achievement of CMR and MFC MRD negativity were independent predictors of both PFS and OS (HR 0.17, CI 0.07-0.42, P & lt; 0.001 and HR 0.21, CI 0.04-0.97, P= 0.046, respectively for PFS and OS). Conclusion: In conclusion, the present analysis confirms the applicability and validity of DS criteria to define PET/CT CMR in an independent prospective series of NDTEMM patients. CMR significantly and independently correlated in uni- and multivariable analysis with patient's outcomes in terms of PFS and OS and was complementary to the MFC MRD negativity. Figure Disclosures Zamagni: Takeda: Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau. Gay:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. D'Agostino:GSK: Membership on an entity's Board of Directors or advisory committees. Galli:Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria; BMS: Honoraria. Zambello:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Rivolti:Celgene: Membership on an entity's Board of Directors or advisory committees. Tacchetti:Bristol-Myers Squibb: Honoraria; AbbVie: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Oncopeptides: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Fanti:Bayer, Astellas, GE Healthcare, ANMI, Janssen: Membership on an entity's Board of Directors or advisory committees; Bayer, Astellas, GE Healthcare, Sanofi, AAA: Honoraria. Boccadoro:Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Cavo:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria. Musto:Amgen: Honoraria; Celgene: Honoraria. Oliva:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-137412

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7