Maria Mainou

Background: Oncology clinical trials, regardless of success in meeting their primary endpoint, often suffer from spin—the misrepresentation of research findings. Despite dramatic improvements in myeloma outcomes, numerous recent myeloma trials have failed to meet their primary endpoints while others have amplified marginally positive findings. A thorough evaluation of reporting practices and spin in myeloma randomized controlled trials (RCTs) is needed. Materials and Methods: We performed a cross-sectional analysis of myeloma RCTs that began enrollment in January 2015 or later, with final search conducted in March 2025. Reporting of prespecified primary endpoints and sample size calculations was abstracted. Two reviewers screened for the presence of spin, defined as at least one reporting practice that could mislead readers by emphasizing benefit or minimizing unfavorable findings. Multivariable logistic regression was used to determine factors associated with spin. The methods were registered on the Open Science Framework. Results: Of 82 screened studies, 71 RCTs were included. The prespecified primary endpoint was statistically significant in 46 trials (64.8%). Sample size calculations were reported in 51 trials (71.8%), and conclusions aligned with primary endpoint results in 63 trials (88.7%). Spin occurred in 25 trials (35.2%), most commonly through optimistic language and emphasis on secondary/subgroup findings. In multivariable analysis, meeting the prespecified primary endpoint was associated with lower odds of spin (adjusted odds ratio [OR] = 0.15; 95% CI, 0.03-0.70; P = .016). Conclusion: Spin affected one-third of contemporary myeloma RCTs and was strongly associated with nonsignificant primary endpoints, highlighting the need for primary endpoint-aligned interpretation and transparent sample size reporting.

Summary: Research in multiple myeloma increasingly relies on surrogate end‐points to expedite approvals, yet these may not reflect patient priorities. We conducted a mixed‐methods study to identify outcomes valued by patients and clinicians and compare them with end‐points used in randomized controlled trials (RCTs). Interviews with 10 patients and 6 clinicians identified treatment priorities, which, together with end‐points from a systematic review of myeloma RCTs, informed tailored surveys, completed by 117 patients and 105 clinicians. Both groups ranked quality of life (QoL) as most important (odds ratio [OR] 1.01; 95% confidence interval [CI] 0.55–1.87). Clinicians more often prioritized overall survival (OS) (OR 1.92; 95% CI 1.05–3.50) and progression‐free survival (PFS) (OR 5.37; 95% CI 1.95–14.79), whereas patients prioritized pain reduction (OR 0.03; 95% CI 0.00–0.23). Compared with RCT end‐points, patients emphasized QoL (OR 0.03; 95% CI 0.01–0.07) and pain elimination (OR 0.05; 95% CI 0.02–0.11), while trials favoured PFS (OR 6.33; 95% CI 2.53–15.83) and response (OR 17.75; 95% CI 5.56–56.61). Clinicians aligned with trials on PFS but valued QoL and OS more highly. QoL emerged as a shared priority, underscoring the need for patient‐centred trial designs that better capture outcomes meaningful to those living with myeloma.

Background: Although myeloma represents a key success story in oncology, some drugs have failed to meet primary endpoints in randomized controlled trials (RCTs), despite promising early phase activity. This analysis aimed to understand factors that increase the likelihood of meeting primary endpoints in myeloma RCTs. Methods: Myeloma RCTs published through October 2023 were identified using MEDLINE, PubMed, Embase, and the Cochrane Registry. Studies were classified as head-to-head (substituting 1 regimen for another) or add-on (adding 1 drug to existing regimen). Trials were considered successful if they achieved statistical significance for primary outcomes. Logistic regression identified predictors of meeting trial endpoints. Results: A total of 145 comparisons from 123 RCTs were included. Only 2 factors were independently associated with meeting primary endpoints in multivariate analysis. Higher median participant age was associated with lower odds of meeting the primary endpoint (odds ratio [OR] per 1-year increase = 0.90, 95% confidence interval [CI] = 0.83 to 0.98). Overall survival (OS) was the primary endpoint in 20 of 145 comparisons, of which 3 of 20 met their endpoint. Selecting OS as primary endpoint was associated with reduced likelihood of success compared with progression-free survival by 94% (OR = 0.06, 95% CI = 0.01 to 0.23). Head-to-head design was not associated with lower success rates than add-on design (OR = 0.59; 95% CI = 0.22 to 1.62). Conclusion: Two key factors predicted higher likelihood of meeting endpoints: younger patient age and primary endpoints other than OS. Although head-to-head design is considered riskier, it was not associated with decreased success. This analysis aims to better inform clinicians, industry, and regulators in myeloma drug development.

Summary: Luspatercept has been approved for the treatment of anaemia in transfusion‐dependent (TD) patients with lower risk (LR) myelodysplastic syndromes (MDS) after erythroid‐stimulated agent (ESA) failure, according to the results of the MEDALIST trial. In this multicentre retrospective study, we report efficacy and safety data of luspatercept administered in 98 TD LR‐MDS patients after ESA failure. The percentage of patients that stopped luspatercept due to adverse events was comparable to that reported in the MEDALIST study. Furthermore, we observed that 44.3% patients who had completed 24 weeks of follow‐up achieved transfusion independence lasting longer than 8 weeks, compared to 38% in the MEDALIST trial. These positive results may be attributed to the inclusion of patients with lower transfusion needs in our study. All responses were observed within 8 months since luspatercept onset and many were long‐lasting, even in the high‐transfusion burden patient group. In addition, response to luspatercept and the presence of less than two mutations independently predicted for longer overall survival. Overall, our results confirm luspatercept's safety and efficacy in TD LR‐MDS patients who have experienced ESA failure in a real‐world setting.

The assessment of health-related quality of life (HRQoL) in thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of transfusion-dependent thalassemia (TDT) patients in Greece. This was a multicentric, cross-sectional study conducted in 2017 involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in the univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower compared to the general population in Greece. The mean summary score of TranQol was relatively high (71 ± 14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment of a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

The assessment of Health-Related Quality of Life (HRQoL) in Thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of Transfusion-Dependent Thalassemia (TDT) patients in Greece. This was a multicentre, cross-sectional study conducted in 2017, involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower, compared to the general population in Greece. The mean summary score of TranQol was relatively high (71±14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment in a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

The present study is an overview of systematic reviews focusing on adverse events of antimyeloma treatments. It provides a systematic description of adverse events as they are reported in the systematic reviews as well as a critical appraisal of included reviews. We conducted a comprehensive literature search in the most widely used electronic databases looking for systematic reviews that had an adverse event of an antimyeloma treatment intervention as primary outcome. Two independent reviewers conducted selection of included studies and data extraction on predesigned online forms and assessed study quality using AMSTAR 2. Overall corrected covered area (CCA) was calculated to examine the overlap of primary studies across systematic reviews. After screening eligible studies, 23 systematic reviews were included in this overview. Seven reviews with overall CCA of 14.7% examined cardiovascular adverse events of different drugs, including immunomodulatory drugs and proteasome inhibitors (mainly carfilzomib). Nine focused on infections, presenting with overall CCA of 5.8%, each one focused on a different drug or drug class. Three studied thromboembolism in patients treated either with lenalidomide, any immunomodulatory drug, or with daratumumab and had an overall CCA equal to 1.5%. Four more reviews focused on bortezomib-associated neurotoxicity, carfilzomib-associated renal toxicity, or second primary malignancies as an adverse event of lenalidomide or anti-CD38 monoclonal antibody treatment. The quality of included studies as judged by AMSTAR 2 was mostly critically low. Absence of a priori registered protocol and formal assessment of risk of bias of included primary studies were the most common shortcomings. Reporting of antimyeloma drug-associated toxicity is supported by multiple systematic reviews; nevertheless, methodological quality of existing reviews is mostly low.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) is a rare paraneoplastic syndrome, and its diagnosis is based on a series of clinical and laboratory findings. We present the case of a 46-year-old woman who was previously diagnosed with essential thrombocythemia. The patient complained about dyspnea on exertion, nausea, burning of the lower limbs, weight loss, recurrent episodes of lower back pain and polymenorrhea. Physical examination revealed hyperpigmentation, livedo reticularis of the lower limbs, sclerodermoid changes and plectrodactyly. A computed tomography-guided bone biopsy revealed the presence of plasmacytoma, and based on a combination of clinical features such as polyneuropathy, a diagnosis of POEMS syndrome has been established. The diagnosis of POEMS syndrome demands a high index of suspicion, especially in cases of peripheral neuropathy, peripheral edema or organomegaly of unknown origin. Since the syndrome can be fatal, early diagnosis is pivotal for patients’ survival and quality of life.