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BackgroundThe whole-body low-dose CT (WBLDCT) is the first-choice imaging technique in patients with suspected plasma cell disorder to assess the presence of osteolytic lesions. We investigated the performances of an optimized protocol, evaluating diagnostic accuracy and effective patient dose reduction using a latest generation scanner.Methods and MaterialsRetrospective study on 212 patients with plasma cell disorders performed on a 256-row CT scanner. First, WBLDCT examinations were performed using a reference protocol with acquisition parameters obtained from literature. A phantom study was performed for protocol optimization for subsequent exams to minimize dose while maintaining optimal diagnostic accuracy. Images were analyzed by three readers to evaluate image quality and to detect lesions. Effective doses (E) were evaluated for each patient considering the patient dimensions and the tube current modulation.ResultsA similar, very good image quality was observed for both protocols by all readers with a good agreement at repeated measures ANOVA test (p>0.05). An excellent inter-rater agreement for lesion detection was achieved obtaining high values of Fleiss’ kappa for all the districts considered (p<0.001). The optimized protocol resulted in a 56% reduction of median DLP (151) mGycm, interquartile range (IQR) 128–188 mGycm vs. 345 mGycm, IQR 302–408 mGycm), of 60% of CTDIvol (2.2 mGy, IQR 1.9–2.7 mGy vs. 0.9 mGy, IQR 0.8–1.2 mGy). The median E value was about 2.6 mSv (IQR 1.7–3.5 mSv) for standard protocol and about 1.5 mSv (IQR 1.4–1.7 mSv) for the optimized one. Dose reduction was statistically significant with p<0.001.ConclusionsProtocol optimization makes ultra-low-dose WBLDCT feasible on latest generation CT scanners for patients with plasma cell disorders with effective doses inferior to conventional skeletal survey while maintaining excellent image quality and diagnostic accuracy. Dose reduction is crucial in such patients, as they are likely to undergo multiple whole-body CT scans during follow-up.

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Introduction: Risk-adapted therapy in curable hematologic malignancies is commonly applied: low-risk patients (pts) may be cured with less intensive treatment, avoiding excessive toxicity, whereas high-riskpts require more intensive and toxic regimens. In multiple myeloma (MM), this model may not apply, since the disease is incurable. In recent years, there has been a marked improvement in patient outcome, due to the introduction of novel agents and optimized treatment strategies, including the use of transplant and maintenance. A better evaluation ofpts prognosis based on the new revised international staging system (R-ISS) has been also introduced in clinical practice. The objective of this analysis was to evaluate the impact of treatment intensification (specifically autologous stem cell transplantation [ASCT] and maintenance) inpts with different prognostic features. Methods: Data from 3 phase III randomized trials in newly diagnosed MMpts (RV-MM-209; EMN441; GIMEMA-MM0305) were pooled together and analyzed. Baseline patient risk assessment was estimated using R-ISS. We evaluated: 1) the impact of treatment intensification with high-dose therapy followed by ASCTvs no-ASCT inpts with R-ISS Stage Ivs Stage II/III; 2) the impact of treatment intensification with maintenancevs no maintenance inpts with R-ISS Stage Ivs Stage II/III. RV-MM-209 and EMN441 studies randomizedpts to ASCTvs no-ASCT; allpts in the GIMEMA-MM0305 trial did not receive ASCT and were excluded from the first comparison; RV-MM-209 and GIMEMA-MM0305 studies randomizedpts to maintenance or no maintenance after induction/consolidation; allpts in the EMN441 trial received maintenance and were excluded from the second comparison. We evaluated progression free survival-1 (PFS1), PFS2 and overall survival (OS). Cox proportional hazards models were used to estimate hazard ratios (HRs). To account for potential confounders, the comparisons between ASCTvs no-ASCT and maintenancevs no maintenance were adjusted for the trial effect and the main prognostic features. Results: Overall, 1302 pts were enrolled in the 3 trials. Median follow-up was 4 years.Comparison ASCTvs no-ASCT: 791pts were enrolled in the 2 trials, 529 were eligible for the ASCTvs no ASCT comparison. R-ISS Stage data were available for 419 pts. There was an overall advantage for ASCTvs no-ASCT in PFS1 (0.53; p<0.001), PFS2 (HR 0.53; p<0.001) and OS (HR 0.51; p<0.001). The 4-year PFS1 was 53% inpts with R-ISS Stage I randomized to ASCT, 35% inpts with R-ISS Stage II/III randomized to ASCT, 36% inpts with R-ISS Stage I randomized to no-ASCT and 19% in those with R-ISS Stage II/III randomized to no-ASCT (p<0.001); the 4-year PFS2 was 83%, 60%, 71% and 43% in the 4 subgroups, respectively (p<0.001) (Figure 1A, B); the4-year OS was 95%, 75%, 88% and 61%(p<0.001). Comparison maintenancevs no maintenance: 913pts were enrolled in the 2 trials, 550 could be eligible for maintenance. R-ISS data were available in 403 pts. Maintenance significantly improved PFS (HR 0.54, p<0.001), PFS2 (HR 0.52, p<0.001) and OS (HR 0.69, p=0.027) in comparison with no maintenance. The 4-year PFS was 48% forpts with R-ISS Stage-I assigned to maintenance, 37% forpts with R-ISS Stage II/III assigned to maintenance, 25% forpts with R-ISS Stage-I assigned to no maintenance and 18% forpts with R-ISS Stage II/III assigned to no maintenance (p<0.001); the 4-year PFS2 was 73%, 66%, 59% and 43% in the 4 subgroups, respectively (p<0.001) (Figure 1C, D); the 4-year OS was 80%, 73%, 77% and 63% (p<0.001). Conclusions: Both ASCT and maintenance improved PFS1, PFS2 and OS in MM pts. The highest survival was reported in patients with R-ISS Stage I receiving ASCT and/or maintenance. Low-riskpts (R-ISS Stage I) not undergoing intensification with ASCT or maintenance lose their prognostic advantage over high-risk patients receiving the same intensification. Figure 1. Figure 1. Disclosures Gay: Janssen-Cilag: Other: Advisory Board; Celgene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Takeda: Honoraria, Other: Advisory Board; Mundipharma: Other: Advisory Board. Hajek:Novartis: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Onyx: Consultancy; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Bringhen:Mundipharma: Other: Advisory Board; Karyopharm: Other: Advisory Board; BMS: Honoraria; Janssen-Cilag: Honoraria; Amgen: Other: Advisory Board; Celgene: Honoraria. Gaidano:Gilead: Consultancy, Honoraria, Speakers Bureau; Morphosys: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Caravita:Janssen-Cilag: Honoraria. Cavo:Millennium: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Foà:Pfizer: Speakers Bureau; Ariad: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; Genetech: Consultancy; Roche: Consultancy, Speakers Bureau. Patriarca:Bristol-Myers Squibb: Other: Advisory board; Mundipharma: Other: Advisory board; Janssen-Cilag: Other: Advisory board; MSD: Consultancy; Celgene: Consultancy. Ria:Italfarmaco: Consultancy, Speakers Bureau; Janssen-Cilag: Other: Advisory Board, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Binding Site: Speakers Bureau; BMS: Speakers Bureau; BMS: Speakers Bureau. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Boccadoro:Novartis: Honoraria, Research Funding; Mundipharma: Research Funding; SANOFI: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Abbivie: Honoraria; Amgen: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; BMS: Honoraria, Research Funding.