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PURPOSE 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95). PATIENTS AND METHODS Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes. RESULTS At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively) CONCLUSION FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.

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.

Carfilzomib–lenalidomide–dexamethasone (KRd) has been approved for the treatment of relapsed/refractory multiple myeloma (RRMM). We conducted a retrospective analysis of 197 RRMM patients (pts) between January 2016 and March 2018 in six Italian hematologic centers, with the aim to evaluate efficacy and safety of KRd in real‐life. At KRd initiation 27% carried high risk cytogenetic abnormalities (HRCA) [del17p and/or t(4;14) and/or t(14;16)], median number of prior lines of therapy was 2 (1–8), nearly all pts (96%) received prior bortezomib (18% refractory) while 45% were exposed to lenalidomide (R; 22% refractory). At the median of 12.5 months, 52% of the pts had discontinued treatment, mainly (66%) for progression. Main grade 3–4 adverse events were neutropenia (21%), infections (11%), and hypertension (6%). Overall, the response rate was 88%. The median progression‐free survival (PFS) was 19.8 months and 1‐year overall survival (OS) rate was 80.6%. By subgroup analysis, extended PFS and OS were observed for pts who received ≤2 prior lines of therapy (HR = 0.42, p < 0.001 and HR = 0.35, p = 0.001, respectively), not refractory to prior R (HR = 0.37, p < 0.001, and HR = 0.47, p = 0.024), without HRCA (HR = 0.33, p = 0.005 and HR = 0.26, p = 0.016) and achieving ≥ very good partial response (VGPR; HR = 0.17, p < 0.001 and HR = 0.18, p < 0.001). In conclusion, KRd demonstrated to be effective in RRMM pts treated in real‐world setting, without new safety concerns. Better survival outcomes emerged for pts with ≤2 prior lines of therapy, achieving at least a VGPR, and without HRCA.

Background Pain-related self-efficacy is defined as the beliefs held by people with chronic pain that certain activities can be carried out despite the pain. Poor self-efficacy is an obstacle to the recovery and predicts long-term disability. The aims of this study are to investigate the prevalence of poor pain self-efficacy in Italian subjects with chronic low back pain (LBP), and to inquire the relationships between self-efficacy, disability, pain, and main demographic and clinical characteristics. Methods A secondary multicenter retrospective analysis was done on 310 outpatients with chronic non-specific LBP. The pain self-efficacy measured with the Pain Self-Efficacy Questionnaire (PSEQ), the disability measured with the Roland & Morris Disability Questionnaire, and the pain intensity measured with the Numerical Rating Scale were considered variables to investigate, whereas demographic and clinical variables were considered predictors or potential confounders. A 40/60 PSEQ score was adopted as cut-off to distinguish between good and poor self-efficacy. Results 199 subjects (64.2% of the sample) showed poor self-efficacy. The odds of having poor self-efficacy appeared significantly related to female gender (OR = 1.80, 95%CI [1.12;2.90]; p = 0.015) and drugs use (OR = 1.68, 95%CI [1.06;2.70]; p = 0.029). Significant relationships also emerged between disability and higher age (β = 0.07, 95%CI [0.01; 0.12]; p = 0.02), being female (β = 1.80, 95%CI [0.32;3.29]; p = 0.018), low educational level (β = − 1.68, 95%CI [− 2.59;-3.29]; p < 0.001), higher height (β = − 0.08, 95%CI [− 0.158;-0.002]; p = 0.045), pain duration [mos] (β = 0.01, 95%CI [0.001;0.021]; p = 0.041), and drugs use (β = 2.86, 95%CI [1.44;4.27]; p < 0.001). The amount of pain appeared significantly related to educational level (β = − 0.47, 95%CI [− 0.76;-0.182]; p < 0.001), smoking (β = 0.56, 95%CI [0.09; 1.03]; p = 0.021), height (β = − 0.03, 95%CI [− 0.05; − 0.002]; p = 0.036), and drugs use (β = 0.81, 95%CI [0.399;1.22]; p < 0.001). No significant correlation appeared among weight, body mass index, and referred pain neither in relation to self-efficacy, nor in relation to pain/disability. Conclusions The majority of our sample, composed of Italian people complained of chronic LBP, shows poor self-efficacy. Female gender and drugs use are significantly related to poor self-efficacy, low educational level negatively influences the amount of perceived pain and disability, and older age and smoking are related to disability and pain intensity, respectively. The knowledge of these sociodemographic and clinical characteristics potentially influencing chronic LBP may be useful to address more efforts towards the most negatively impacted subjects, among the entire population complained of chronic LBP.