PURPOSE:Owing to prolonged treatment exposure, patients with relapsed/refractory multiple myeloma (RRMM), particularly those with low socioeconomic status (SES), may be especially vulnerable to financial toxicity (FT), which can negatively affect their health-related quality of life (HRQoL). We aimed to evaluate the association between SES and HRQoL in patients with RRMM and to explore the mediating role of FT in this relationship. METHODS:We conducted a cross-sectional analysis of baseline data from a multicenter, prospective, observational study of patients with RRMM in Italy and the United Kingdom. SES was assessed via a composite index including education, employment, and living arrangements. We evaluated HRQoL using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and QLQ-MY20. Multivariable regression models adjusted for potential confounders were used to assess the association between SES and HRQoL. Mediation analysis was conducted to examine the role of FT in the relationship between SES and HRQoL. RESULTS:A total of 505 patients with RRMM were analyzed, and 15.6%, 49.3%, and 35.1% were classified as low, middle, and high SES, respectively. Patients with low versus high SES reported clinically meaningful worse scores in 11 EORTC QLQ-C30 scales and in the QLQ-MY20 disease symptoms scale. Compared with patients with high SES, those with low SES had significantly higher odds of reporting clinically important pain (odds ratio [OR], 3.55), financial difficulties (OR, 2.97), and impaired physical functioning (OR, 2.96). FT significantly and partially mediated the relationship between SES and HRQoL, accounting for 46.3% of the total effect. CONCLUSION:Patients with RRMM and low SES experienced worse HRQoL compared with those with higher SES, with FT partially mediating this association. Interventions addressing FT and broader social determinants of health in RRMM are warranted to reduce disparities and promote equity in cancer outcomes.

BACKGROUND:Chimeric antigen receptor (CAR) T cells have shown considerable promise in treating patients with haematological malignancies. We aimed to investigate short-term patient-reported symptomatic adverse events in patients with aggressive B-cell lymphomas treated with CAR T-cell therapy and compare them with those reported by their treating physicians. We also examined factors predicting overall short-term burden of therapy. METHODS:This was a prospective, observational, multicentre study enrolling patients across 13 centres in Italy. Eligible patients were aged 18 years and older with a confirmed diagnosis of aggressive B-cell lymphoma. All patients were scheduled to undergo CAR T-cell therapy with one of the following products: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or brexucabtagene autoleucel (brexu-cel). The primary objective of this analysis was to assess the prevalence of short-term patient-reported symptomatic adverse events overall and by sex and age categories. The primary objective was evaluated on day 10 after infusion via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which includes 19 items selected based on their clinical relevance, including: difficulty swallowing, decreased appetite, nausea, diarrhoea, swelling, hair loss, dizziness, concentration difficulty, memory difficulty, general pain, headache, muscle pain, joint pain, insomnia, fatigue, anxiety, discouragement, sadness, and chills. Prevalence of symptomatic adverse events was also assessed by type of CAR T-cell product. Additionally, the study was designed to allow a corresponding adverse event assessment via the CTCAE by treating haematologists for comparative analysis. Adverse events reported by physicians were matched with corresponding adverse events reported by patients. Furthermore, an overall symptom burden score was computed and used as outcome variable in multivariable analysis to examine factors predicting short-term burden of therapy, including sociodemographic and clinical data and pre-infusion patient-reported physical functioning by the EORTC QLQ-C30. The study is registered with ClinicalTrials.gov, NCT06026644, and is closed to accrual and follow-up is complete. FINDINGS:Between June 29, 2022, and Feb 26, 2024, 170 patients were included in the study. The median age of patients was 61·1 years (IQR 51·1-68·5) and the median follow-up was 23·7 months (17·7-24·6). 53 (31%) of 170 enrolled patients were female and 117 (69%) were male. Most patients were diagnosed with diffuse large B-cell lymphoma (118 [69%] patients), followed by mantle cell lymphoma (32 [19%] patients) and primary mediastinal large B-cell lymphoma (20 [12%] patients). 98 (58%) patients were infused with axi-cel, 39 (23%) with tisa-cel, and 32 (19%) with brexu-cel. 165 patients reached the day 10 timepoint, of whom 143 (87%) completed the corresponding PRO-CTCAE item list. We observed a prevalence (any grade) of more than 50% across 12 of the 19 symptomatic adverse events examined: fatigue (123 [87%] of 141 patients), decreased appetite (116 [83%] of 139 patients), insomnia (112 [79%] of 142 patients), chills (103 [73%] of 142 patients), diarrhoea (99 [70%] of 141 patients), sadness (81 [57%] of 141 patients), general pain (78 [55%] of 143 patients), dizziness (78 [55%] of 143 patients), joint pain (74 [52%] of 142 patients), muscle pain (73 [51%] of 143 patients), headache (73 [51%] of 143 patients), and impaired concentration (72 [51%] of 142 patients). Inspection of moderate to severe grades revealed that more than 30% of patients reported fatigue (78 [55%] of 141 patients), decreased appetite (74 [53%] of 139 patients), diarrhoea (63 [45%] of 141 patients), chills (49 [35%] of 142 patients), and insomnia (44 [31%] of 142 patients). Physicians frequently under-reported symptoms in their patients. For example, gastrointestinal symptoms were consistently under-reported, including difficulty swallowing (28 [78%] of 36 patients), decreased appetite (75 [77%] of 98 participants), nausea (43 [70%] of 61 participants), and diarrhoea (60 [71%] of 85 participants). INTERPRETATION:Our findings could assist clinicians in delivering more targeted and timely supportive care interventions and might inform patients about anticipated symptoms during the early post-CAR T-cell infusion period. Moreover, the observed discrepancies between patient-reported and clinician-reported symptoms suggest that more systematic use of patient-reported outcome measures might provide complementary insights beyond those captured through clinician assessment. FUNDING:Fondazione GIMEMA Franco Mandelli Onlus and Novartis Farma Italy.

Abstract Myelodysplastic syndromes (MDS) are clinically and biologically diverse disorders, emphasizing the need for personalized treatment approaches. The International Working Group for Prognostication of MDS (IWG_PM) recently introduced a molecular classification, referred to as the MDS taxonomy, that categorizes patients into 16 subgroups based on 21 gene mutations, 6 cytogenetic abnormalities, and loss of heterozygosity (LOH) at TP53 and TET2 loci. This study sought to validate and enhance the clinical relevance of the MDS taxonomy by analyzing a large retrospective cohort (n = 5136) and transcriptomic data from a prospective cohort (n = 477). The taxonomy successfully identified subgroups with distinct clinical characteristics and disease progression patterns. However, incorporating gene interactions from taxonomy subgroups did not improve the prognostic performance of the Molecular International Prognostic Scoring System (IPSS‐M). We further assessed whether the taxonomy could guide management in patients receiving disease‐modifying therapies. Except for the “TP53‐complex” subgroup, taxonomy classifications were not predictive of hypomethylating agent response or transplant outcomes. Nonetheless, they correlated with overall survival, suggesting that while both IPSS‐M and the taxonomy capture disease biology, other non‐genetic factors may influence treatment response. RNA sequencing confirmed the biological distinctiveness of the taxonomy groups. Transcriptomic profiling of CD34+ bone marrow cells revealed unique, homogeneous gene expression patterns, particularly within the AML‐like, biTET2, SF3B1, and TP53‐complex subgroups. Further integration of multi‐omics data may refine MDS classification, improving clinical decision‐making and guiding the development of targeted therapies.

CONTEXT:Early palliative care (EPC) improves patient-centered outcomes in solid tumors but remain underutilized in acute myeloid leukemia (AML), where evidence on EPC content and implementation is limited. OBJECTIVES:We aimed to characterize the core components...associations with palliative care quality indicators and end-of-life (EOL) care intensity. METHODS:We conducted a single-center retrospective observational study including consecutive adults with AML/HR-MDS receiving outpatient EPC. We reviewed electronic medical records to identify EPC components across all visits. We assessed temporal trends by comparing the first versus last three visits. Mixed-effects logistic regression examined associations between EPC components and quality indicators; univariate models assessed associations with EOL care aggressiveness. RESULTS:A total of 180 patients received 1175 EPC visits (median six visits/patient). EPC components most frequently addressed symptoms (89.9%), coping support (74.6%), and illness understanding (71.2%). Over time, EOL planning increased (11.0% in first vs. 68.3% in last three visits; P < 0.001), as did family engagement (45.2% vs. 61.9%; P = 0.025). In multivariable models, more illness-understanding visits increased prognostic awareness discussions (OR 1.34; 95% CI: 1.16-1.55; P < 0.001), whereas coping-focused visits were associated with lower odds of documented goals-of-care conversations (OR 0.86; 95% CI: 0.78-0.96; P = 0.006). More EOL planning-focused visits increased the likelihood of receiving ≥1 quality indicator (OR 1.65; 95% CI: 1.40-1.94; P < 0.001) and ACP documentation (OR 2.91; 95% CI: 2.25-3.76; P < 0.001). Higher EPC exposure was associated with lower chemotherapy use in the last 30 days of life (OR 0.73; 95% CI: 0.53-1.00; P = 0.049), and coping-focused visits were associated with lower odds of in-hospital death (OR 0.77; 95% CI: 0.60-0.94; P = 0.010). CONCLUSIONS:EPC in AML/HR-MDS has distinct components that vary over time and are associated with established indicators of high-quality care, including EOL outcomes. These findings support a scalable, content-driven EPC model with direct implications for clinical implementation and future trials in hematologic malignancies.

OBJECTIVES:To describe longitudinal changes in quality of life (QOL) and symptoms among patients with acute myeloid leukaemia (AML) receiving real-world early palliative care (EPC) during the first year after diagnosis. METHODS:This prospective observational study enrolled consecutive adults with AML followed in an outpatient EPC clinic. QOL and symptoms were assessed monthly using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), the Edmonton Symptom Assessment Scale (ESAS) and the Hospital Anxiety and Depression Scale (HADS). Scores were analysed through joint modelling, integrating longitudinal and survival data, and sensitivity analyses. RESULTS:Thirty-eight patients contributed 169 FACT-Leu, 151 ESAS and 111 HADS questionnaires. From baseline, median FACT-Leu scores improved from 108.7 to 135.7 at 4 months and remained stable through 8 and 12 months (p≤0.011), while ESAS scores decreased from 25.2 to 5.7 by 4 months and remained low through 12 months (p<0.001), indicating sustained symptom improvement. HADS scores showed no statistically significant changes, although a modest anxiety improvement was noted. Trajectories remained consistent across all sensitivity analyses. CONCLUSIONS:In AML patients receiving EPC in a real-world outpatient setting, QOL and symptom burden showed sustained improvement over time. These descriptive findings highlight the potential effectiveness and clinical relevance of EPC in routine AML care and provide real-world reference data for future controlled studies.

Decitabine, including its new oral formulation (decitabine-cedazuridine, DEC-C), is commonly used in AML and MDS, particularly in older or unfit patients. While its clinical efficacy and tolerability are well documented, evidence regarding patient-reported outcomes (PROs) and health-related quality of life (HRQoL) remains limited. We conducted a review of the available literature on PROs in patients with AML and MDS treated with decitabine, with the aim of evaluating its impact on HRQoL, symptom burden, and patient preferences. A systematic literature search of PubMed up to October 2024 identified studies evaluating HRQoL or PROs in adult AML and/or MDS patients receiving decitabine, regardless study design. Ten studies met the inclusion critera. Decitabine-based regimens were associated with preservation of HRQoL compared with intensive chemotherapy and improvements in fatigue and physical functioning versus best supportive care. In patients with AML, baseline HRQoL scores were found to be predictive of survival outcomes. Surveys consistently indicated strong patient preference for oral DEC-C due to reduced treatment burden and greater convenience, though longitudinal data remain limited. In conclusion, currently available HRQoL evidence for decitabine provides meaningful insight to guide further research. Findings from patient surveys and the availability of decitabine in both intravenous and oral formulations emphasize new treatment aspects that can be effectively captured through PROs. Their systematic integration may help uncover critical issues such as symptom burden, adherence, and patient priorities, ultimately fostering more patient-centered care.

OBJECTIVES:To explore stakeholder perspectives related to open-label bias in patient-reported outcomes (PROs) from cancer randomized controlled trials and identify possible risk factors for such bias. This study represents the first phase of the Importance of Patient-Reported Outcomes in Cancer Clinical Trials: Evaluating the Effects of Therapy Masking (IMPROvE) project, an international initiative investigating the impact of trial design (ie, open-label vs blinded trials) on PRO results. METHODS:Semistructured interviews were conducted with 20 stakeholders, including PRO experts (researchers, oncologists, and statisticians) and patients from 7 countries. An interview guide addressed perceptions, experiences, and views on potential contributors of open-label bias in PROs. Thematic content analysis was used to identify recurrent themes and patterns. Findings were complemented with a targeted narrative literature review. RESULTS:Stakeholders expressed divergent views regarding the presence and magnitude of open-label bias in PROs. Patient expectations, treatment type, disease stage, and clinician-patient interactions were frequently mentioned as potential contributors to such bias. Although experts often framed open-label bias as a methodological concern, patients highlighted experiential and relational aspects. Both groups acknowledged that robust trial methodology and validated PRO instruments may mitigate risks. Literature findings were consistent with these perspectives, highlighting careful methodological planning and transparent reporting practices as critical to mitigate risk of bias. CONCLUSIONS:This study offers insights into stakeholder perspectives on potential open-label bias in PROs from cancer randomized controlled trials, highlighting both methodological and experiential dimensions. These exploratory findings may inform future evidence generation and guide the development of an "open-label bias PRO checklist."

Acute Myeloid Leukemia (AML) is a heterogeneous group of aggressive blood-related cancers that arise from the hematopoietic system, requiring specific treatments due to their genetic diversity and complexity. Artificial intelligence (AI) has emerged as a transformative technology in healthcare, with considerable potential to help manage AML. The application of AI approaches, such as Machine Learning (ML) models and Deep Learning (DL) algorithms, has been shown to aid risk stratification, diagnosis, treatment planning, and surveillance. This review highlights recent developments in AI applications for the personalized management of AML. We focus specifically on three major axes of personalization in AML: (1) the use of predictive models combining different data sources to improve prognostic assessment and guide risk-adaptive treatments; (2) prediction of treatment responses to various therapies based on data analysis; and (3) the use of AI for monitoring and adaptive trials in AML patients.

BACKGROUND:Despite improvements in survival outcomes for acute myeloid leukemia (AML), limited evidence is available on health-related quality of life (HRQoL) and health problems experienced by long-term survivors. PATIENTS AND METHODS:This international, cross-sectional study evaluated HRQoL, comorbidities, and lifestyle behaviors among long-term AML survivors enrolled from 24 centers across 6 countries. Health-related quality of life was assessed using the SF-36 and the EORTC QLQ-C30 questionnaires, while comorbidities were measured with an adapted version of the validated self-administered comorbidity questionnaire. Lifestyle factors, including physical activity, diet, smoking, alcohol consumption, and body mass index, were also assessed. RESULTS:Overall, 225 AML survivors were enrolled, with a median time since diagnosis of 8.8 years (IQR 6.4-11.9) and a median age of 58.9 years (IQR 49.0-67.0). Compared with the general population, AML survivors exhibited clinically relevant impairments in SF-36 physical functioning (Δ = -8.09, P < .001) and role physical scales (Δ = -11.09, P < .001), as well as clinically relevant lower physical component summary scores (Δ = -3.94, P < .001). Survivors treated with alloSCT reported worse HRQoL profiles compared with those treated with autoSCT or chemotherapy only. Comorbidities were highly prevalent (88.5%), with impaired vision, back pain, and arthrosis/arthritis being the most frequent. Analysis of lifestyle behaviors showed that 66.2% of AML survivors were physically inactive, 80.2% did not meet dietary recommendations, and 55.3% were overweight/obese. Multivariate analysis identified physical inactivity as the only independent factor associated with worse HRQoL (β = -6.3, P < .001). CONCLUSION:Our study shows that AML survivors experience physical limitations and a high comorbidity burden even many years after diagnosis, and it provides insights to better inform survivorship care programs. Further research examining the relationship between physical activity and HRQoL in long-term AML survivors is warranted.

BACKGROUND:Patients with acute leukemia frequently receive aggressive treatments near the end of life (EOL) . Goals-of-care (GOC) conversations may improve EOL quality, yet few studies have investigated their impact in hematological malignancies. OBJECTIVE:To evaluate sociodemographic and clinical factors associated with GOC conversations and the impact of GOC conversations on EOL care. METHODS:A retrospective study was conducted among patients with acute leukemia and high-risk myelodysplastic syndromes, treated over a 15-year period at authors' Institution. RESULTS:Of 390 patients, 44.4% had GOC conversations. Palliative care specialists documented the first GOC discussion in 157 patients. 133 (76.9%) patients received GOC conversations within a program of early palliative care (EPC) . In multivariable analysis, age≥60 (OR 4.85; 95% CI: 2.18-10.78) , ≥2 comorbidities (OR 2.52; 95% CI: 1.03-6.2) , non-White race (OR 7.97; 95% CI: 1.13-56.32) , prior allogeneic transplantation (OR 8.74; 95% CI: 2.09-36.58) , and EPC integration (OR 16.28; 95% CI: 4.21-62.92) were significantly associated with higher likelihood of GOC discussions. Concerning EOL care, GOC conversations were associated with reduced odds of chemotherapy in the last 90 days (OR 0.41; 95% CI: 0.21-0.79) , ICU admission in the last 30 days (OR 0.20; 95% CI: 0.05-0.85) , and in-hospital death (OR 0.35; 95% CI: 0.18-0.69) . CONCLUSIONS:GOC conversations were infrequently performed and the primary factor that increased their likelihood of occurrence was EPC. When GOC conversations took place, patients experienced higher-quality EOL care. These results support increasing EPC for patients with hematologic malignancies to improve GOC conversations and their overall EOL care and, suggest EPC as a prime intervention for trials in this setting.

Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied. Phase 3 trials should be less restrictive than early-phase trials to represent the real-world population as closely as possible. We hypothesize that many clinical trials, particularly phase 3 trials, have unnecessarily restrictive eligibility criteria. This study aims to evaluate the most common eligibility criteria according to phase of trial and to determine whether criteria correspond with drug safety signals. We identified MDS clinical trials registered on ClinicalTrials.gov from 1 January 2000 to 1 September 2023 and analyzed the eligibility criteria of 191 therapeutic MDS trials. We found that categorical inclusion and exclusion criteria are remarkably similar in representation across trial phases. Additionally, only 13% of trials are concordant with drug safety signals, suggesting that the eligibility criteria are often arbitrary. On behalf of the icMDS (International Consortium for Myelodysplastic Syndromes), an association of international MDS experts, we provide a position statement on restrictive eligibility criteria for MDS clinical trials that should be avoided with the aim of removing barriers to clinical trial enrollment.

Background:VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) is a recently discovered syndrome of autoinflammatory origin affecting mainly older patients with a clinical picture encompassing a variety of hematological and rheumatological conditions. We aimed to gather current knowledge on patient-reported outcomes (PRO) and morbidity burden of VEXAS patients. Methods:A scoping review conducted via PubMed (last updated September 2024) identified studies involving VEXAS patients, excluding studies primarily addressing hematologic adverse events or laboratory parameters, with no lower date restriction. A double-review process was applied from screening to data charting. Outcomes included the prevalence of manifestations of VEXAS-related morbidity burden and their aggregated rates, adhering to the PRISMA-ScR guidelines. Findings:Out of 357 records, 31 studies met the inclusion criteria, analyzing 1437 patients. The median study sample size was 40 patients (IQR 16-59). Most studies (96·8%) were non-interventional and mostly conducted in France (38·7%) and the USA (32·3%). The median age at symptom onset was 67 years (IQR 66-68·6). Myelodysplastic syndrome was the most common concomitant disease, present in 93·6% of studies. No studies documenting PROs were identified. Skin and pulmonary involvement were the most frequently reported manifestations, appearing in 100% and 96·8% of studies, respectively. Moreover, skin lesions had the highest median prevalence (83·6%, IQR 76-90), followed by fever (81·2%, IQR 67·5-89) and general constitutional symptoms (76%, IQR 54·8-85·3). All symptoms identified in this review were clinician-reported. Interpretation:Our findings may provide preliminary insights into future PRO assessment strategies for VEXAS syndrome. We also advocate for international concerted efforts for a rapid uptake of PRO evidence-based data that can help inform the development of patient-centric therapies for this rare disease. Funding:This work was supported by AIRC5×1000 call "Metastatic disease: the key unmet need in oncology" to MYNERVA project, #21267 Myeloid Neoplasms Research Venture AIRC. Detailed description is available at http://www.progettoagimm.it.

Background Socioeconomic status (SES) is a known factor frequently associated with health-related quality of life (HRQoL) in oncology, yet its impact in the setting of myelodysplastic syndromes/neoplasms (MDS) remains underexplored. Patients with higher-risk MDS may be particularly vulnerable in this respect, considering the high burden of symptoms and functional impairments imposed by the disease already at the time of diagnosis. Objectives The primary objective of this analysis was to examine the prevalence of clinically important problems and symptoms in newly diagnosed patients with higher-risk MDS by their SES. The secondary objective was to assess the risk of impaired functioning and symptoms by different SES groups. Methods We conducted a cross-sectional analysis of adult patients with newly diagnosed higher-risk MDS (according to the IPSS-R) enrolled in a large international prospective observational study by the GIMEMA. The SES was determined using three variables: level of education, employment status, and living arrangements. Each variable was scored as 0 (for low level of education, living alone, or no income) or 1 (for intermediate/high level of education, living with others, or receiving a salary/pension). The final SES index was computed by summing the scores for each variable, and each patient was classified into three categories: low (score 0-1), middle (score 2), and high SES (score 3). To assess HRQoL, all participants completed the EORTC QLQ-C30 at study entry. Prevalence of clinically important problems and symptoms were assessed using established thresholds for the QLQ-C30 (Giesinger JM et al. J Clin Epidemiol 118:1-8, 2020). This prevalence reflects the number of patients in each SES group reporting clinically important problems or symptoms that limit their daily lives, cause worry to them, or require help or care. Logistic regression models were used to assess the risk of impaired functioning or symptoms in the low and middle SES groups vs the high SES group. These models were adjusted for the following potential confounders: age, sex, time since diagnosis, transfusion dependency, ECOG performance status, and HCT comorbidity index. Results Overall, 521 patients with higher-risk MDS were analyzed. The SES was available for 504 patients, who had a median age of 73 years (IQR 65.9-78.8) and a median time since diagnosis of 0 weeks (IQR 0-4.3). Almost half of them were classified as high SES (45.4%), 41.5% as middle SES, and 13.1% as low SES. Prevalence of clinically important problems was higher in the low SES group with respect to middle and high SES groups, across all the QLQ-C30 scales. For example, more than half of patients (59.1%) in the low SES group reported a clinically important level of fatigue, while this prevalence was 47.4% and 39.3% in the middle and high SES groups, respectively (p=0.013). Prevalence of clinically important pain was 53%, 39.2% and 27.1% in low, middle and high SES, respectively (p<0.001). Three out of four (74.2%) patients in the low SES group had a clinically important dyspnea, while this was 58.9% and 57.6% in the middle and high SES, respectively (p=0.045). In the functioning scales, the prevalence of clinically important problems in physical functioning was similar in the low (77.3%) and middle (74.2%) SES groups, but lower in the high SES group (60.3%) (p=0.002). For the cognitive functioning scale, the prevalence of clinically important problems was 43.9%, 32.5% and 25.8% in the low, middle and high SES groups, respectively (p=0.015). Logistic regression analyses revealed a similar trend, with low SES more likely to report impaired functioning or symptoms than those with high SES, independently of potential confounders. For example, patients in the low SES group had a statistically significant higher risk of reporting impaired pain (OR=2.84, 95% CI 1.55-5.24; p<0.001), dyspnea (OR=1.98, 95% CI 1.06-3.83; p=0.037) and cognitive functioning (OR=1.86, 95% CI 1.00–3.42; p=0.047). Conclusions We observed that newly diagnosed patients with higher-risk MDS who have a low SES tend to report worse HRQoL outcomes compared to those with middle or high SES, suggesting that these patients are most in need of special attention. Future research should investigate whether such socioeconomic inequalities may also impact long-term treatment outcomes.

Standardized reporting of clinical trials results for MDS is essential to improve clinical interpretation and cross-study comparison. However, reporting of patient characteristics, response criteria, and endpoints in publications is often inconsistent; there is no systemic analysis of MDS trial reporting available. We conducted a systematic review of published MDS trial manuscripts on behalf of the international consortium for MDS (icMDS) to assess variability in reporting practices. We searched ClinicalTrials.gov to identify all clinical trials registered for adults (≥18 years) with MDS that reported results between 2015-2024. Clinical trials that included acute myeloid leukemia (AML) or MDS/myeloproliferative neoplasms (MPN) were included if they enrolled ≥5 MDS patients. We excluded trials without an MDS cohort; non-therapeutic trials; trials focused on transplant interventions; or those which enrolled solid malignancies or other hematologic malignancies (chronic myeloid leukemia or lymphoid diseases). Finally, trials were required to have a manuscript available on Larvol, PubMed, or Google Scholar. Trials were categorized by disease risk (lower-risk [LR] vs. higher-risk [HR]) and trial phase (early phase [EP] vs. late phase [LP]). We identified 502 MDS trials on ClinicalTrials.gov, of which 351 did not meet inclusion criteria and 79 lacked a manuscript. A total of 72 trials (32 EP, 40 LP) with 80 publications (34 EP, 46 LP) were analyzed. Frequently reported baseline characteristics included age (100% EP, 100% LP), disease risk (74% EP, 74% LP), Eastern Cooperative Oncology Group performance status (85% EP, 72% LP), prior treatments (71% EP, 67% LP), and RBC transfusion dependency (32% EP, 70% LP). Less frequently reported characteristics included blood counts (hemoglobin [Hb; 38% EP, 54% LP], platelet count [38% EP, 54% LP], neutrophil count [24% EP and LP]) and bone marrow blasts (29% EP, 43% LP). Although disease risk was widely reported, definitions varied: IPSS and IPSS-R were each reported in 54% of manuscripts, while IPSS-M appeared in only 3%. Cytogenetic risk was separately reported in 39% of manuscripts (38% EP, 39% LP), and mutational data in 45% (47% EP, 43% LP). Responses per IWG 2006 criteria were reported in 84% of manuscripts. The primary endpoint involved safety/tolerability in 85% of EP manuscripts, though definitions were variable; recommended phase 2 dose was the most common (26% of EP manuscripts). In LP trials, primary endpoints were risk-specific: transfusion independence (TI) in 77% of LR, overall response rate (ORR) in 28% of HR, and complete remission (CR) or overall survival (OS) in 22% of HR. In HR manuscripts, CR was reported in 100%, ORR in 73%, hematologic improvement (HI) in 48%, RBC-TI in 23%, and OS in 80%. However, seven different definitions were used for ORR: CR + marrow CR + partial remission + HI per IWG 2006 was most common (35%). Event-free survival was reported in 25%; progression-free survival and relapse-free survival in 13%; and leukemia-free survival in 5%. Early mortality rate was reported in 35% (18% EP, 56% LP) and transplant rate in 58% (50% EP, 67% LP). Only 47% of HR and 90% of LR manuscripts identified HI-eligible patients. In LR-MDS, RBC-TI was reported in 72% of manuscripts but used six definitions. The most common were RBC-TI ≥8 weeks at any time during treatment (24%), ≥8 weeks within 28 weeks of treatment (13%), ≥8 weeks with Hb increase ≥1.0 (4%), ≥12 weeks with Hb increase ≥1.5 (4%), and ≥16 weeks within 24 weeks of treatment (12%). The remainder did not report RBC-TI, did not define it, or used a custom definition not used in another trial. HI was reported in 80% of LR papers with most of those reporting HI using IWG 2006 criteria (90%). Reporting of baseline characteristics, response criteria, and outcomes is inconsistent in MDS clinical trials, with wide variability in response definitions, including ORR and TI. This heterogeneity limits interpretability, hampers historical comparisons and may obscure efficacy signals. Our findings highlight the need for standardized reporting guidelines to ensure clarity and consistency in MDS trial publications. As a next phase of this effort, we will conduct a formal Delphi process among icMDS experts to establish consensus recommendations for minimal and optimal MDS clinical trial reporting in manuscripts by disease risk (LR/HR) and trial phase (EP/LP).

BACKGROUND:Patient-reported outcomes (PROs) are now frequently incorporated into multiple myeloma (MM) randomized controlled trials (RCTs) to help inform clinical decision making. Although the quality of PRO components in cancer RCT protocols is generally recognized as suboptimal, there are limited data on adherence to international quality standards in MM RCT protocols. METHODS:We performed a systematic review to identify MM RCTs published between January 2014 and June 2023 that utilized the EORTC QLQ-C30 questionnaire. The quality of PRO-specific protocol content was evaluated using the SPIRIT-PRO guidelines, which establish key requirements for PRO inclusion in protocols. The framework consists of 16 items: 5 elaborations of the existing SPIRIT checklist and 11 PRO-specific extensions items. The quality of PRO reporting was evaluated using CONSORT-PRO Extension, which comprises 14 items to improve the reporting of PRO data in clinical trials. RESULTS:Our systematic review identified 35 RCTs encompassing 20,612 patients, with 24 trials (69%) having publicly accessible protocols. The median protocol compliance was 7.5 SPIRIT-PRO items. Analysis of 24 protocols showed strong compliance in assessment schedules (96%), PRO domains/instrument justification (79%), and PRO objectives (71%). Intervention deviation procedures were described in 62% of protocols. Half included comprehensive data collection plans, while 58% addressed missing data methods and 42% outlined PRO research questions or multiplicity controls. Notably weak areas included strategies for preventing missing data (38%), and only 8% of protocols detailed PRO monitoring plans, personnel specifications, or eligibility criteria. CONSORT-PRO scores varied across all 35 RCTs (median 11, range 0.5-14). Among the 35 RCTs, while trials showed strong reporting of statistical elements (94% precision estimates, 91% subgroup analyses, 89% intention-to-treat, 86% timepoint completion) and results (80% hypothesized domains, 71% PRO validity, 69% clinical implications, 66% limitations), key PRO-specific components were reported by less than two-thirds of RCTs: only 11% stated PRO hypotheses, 31% specified administration mode, 43% identified domains, 60% addressed missing data, and 63% provided PRO rationale. Two factors were associated with higher reporting quality, both potentially reflecting publication bias: having a secondary PRO-focused paper (p < 0.001) and finding statistically significant EORTC QLQ-C30 differences (p = 0.024). Our multivariable analysis showed no significant association between SPIRIT-PRO scores and CONSORT-PRO scores. CONCLUSION:Despite some foundational strengths of existing MM RCT protocols, gaps exist in PRO methodological specifications, statistical analysis, and clinical interpretation. Our findings may help to better inform PRO implementation in future MM RCT protocols. For example, since missing PRO data can be due to informative censoring, there should be increased attention on considering how to minimize missing data, already at the stage of protocol writing. Our findings regarding predictors of higher reporting quality suggest that trials with significant PRO differences receive systematically better reporting, possibly introducing bias in the available evidence base.

Patients with hematologic malignancies often receive aggressive end-of-life (EOL) care, which may be partly related to hematologists' discomfort with discontinuing aggressive treatments at EOL. It is therefore important to investigate how hematologists perceive EOL care and how this affects their clinical practice. We assessed a cohort of Italian hematological oncologists through a GIMEMA online survey to explore their attitudes toward standard measures of quality EOL care, their opinions on barriers to providing this care, and potential interventions. EOL quality measures were defined acceptable to hematologist if at least 55% of respondents agreed with their suitability. One-hundred eight-six hematologists completed the survey. Hematologists rated 8 of 13 EOL quality measures as highly acceptable, including no new chemotherapy, no intensive care unit admission, no intubation/cardiopulmonary resuscitation in the last 30 days of life, and hospice admission > 7 days before death. Major barriers to quality EOL care included unrealistic patient expectations, clinician concerns about taking away hope, and uncertainty about what to say. Moreover, 73% admitted to being unfamiliar with discussing goals of care (GOC) or advance care planning (ACP). Suggested interventions for improvement included increasing the availability and timely integration of palliative care, and access to home care services. In conclusion, Italian hematologists find most standard EOL quality measures acceptable, they identify barriers to quality care, and are open to interventions, including early integration of palliative care, to improve patients' EOL care. However, they lack familiarity with GOC and ACP discussions, highlighting the need for communication skills training.