Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials

This is an open-access paper.-- et al.Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatmentrelated side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, 95%CI: 1.20-1.72; P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, 95%CI: 1.75-3.64; P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; 1.12- 2.51; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomibthalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.Peer Reviewe

Ultra-Low-Dose Whole-Body Computed Tomography Protocol Optimization for Patients With Plasma Cell Disorders: Diagnostic Accuracy and Effective Dose Analysis From a Reference Center

BACKGROUND: The 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 MATERIALS: Retrospective 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. RESULTS: A 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. CONCLUSIONS: Protocol 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

Melflufen: A Peptide-Drug Conjugate for the Treatment of Multiple Myeloma

Despite the availability of new therapies that have led to improved outcomes for patients with multiple myeloma, most patients will eventually relapse. With triplet and even quadruplet combination therapies becoming standard in the first and second line, many patients will have few treatment options after second-line treatment. Melflufen (melphalan flufenamide) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Once inside the tumor cells, melflufen is hydrolyzed by peptidases to release alkylator molecules, which become entrapped. Melflufen showed anti-myeloma activity in myeloma cells that were resistant to bortezomib and the alkylator melphalan. In early phase studies (O-12-M1 and HORIZON [OP-106]), melflufen plus dexamethasone has demonstrated encouraging clinical activity and a manageable safety profile in heavily pretreated patients with relapsed/refractory multiple myeloma, including those with triple-class refractory disease and extramedullary disease. The Phase III OCEAN study (OP-104) is further evaluating melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma. The safety profile of melflufen is characterized primarily by clinically manageable hematologic adverse events. Melflufen, with its novel mechanism of action, has the potential to provide clinically meaningful benefits to patients with relapsed/refractory multiple myeloma, including those with high unmet needs.The authors received medical editorial support for the development of this manuscript, which was funded by Oncopeptides AB