Objective
To identify determinants of shared decision making in patients with multiple myeloma (MM) to facilitate the design of a program to maximize the effects of shared decision making.
Methods
...This prospective longitudinal study recruited 276 adult patients (52% male, mean age 62.86 y, SD 15.45). Each patient completed the eHealth Literacy Scale (eHEALS), Multidimensional Trust in Health Care Systems Scale (MTHCSS), Patient Communication Pattern Scale (PCPS), and 9‐Item Shared Decision‐Making Questionnaire (SDM‐Q‐9) at baseline and the SDM‐Q‐9 again 6 months later. One family member of the patient completed the Family Decision‐Making Self‐Efficacy (FDMSE) at baseline. Structural equation modeling (SEM) was used to investigate the associations between eHealth literacy (eHEALS), trust in the health care system (MTHCSS), self‐efficacy in family decision making (FDMSE), patient communication pattern (PCPS), and shared decision making (SDM‐Q‐9).
Results
SEM showed satisfactory fit (comparative fit index = 0.988) and significant correlations between the following: eHealth literacy and trust in the health care system (β = 0.723, P < 0.001); eHealth literacy and patient communication pattern (β = 0.242, P < 0.001); trust in the health care system and patient communication pattern (β = 0.397, P < 0.001); self‐efficacy in family decision making and patient communication pattern (β = 0.264, P < 0.001); eHealth literacy and shared decision making (β = 0.267, P < 0.001); and patient communication pattern and shared decision making (β = 0.349, P < 0.001).
Conclusions
Patient communication and eHealth literacy were found to be important determinants of shared decision making. These factors should be taken into consideration when developing strategies to enhance the level of shared decision making.
Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. ...Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.
The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2–6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1–24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).
Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years IQR 69–80). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8–37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks IQR 20–73) versus epoetin alfa (27 weeks 19–55). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).
In this interim analysis, luspatercept improved the rate at which red blood cell transfusion independence and increased haemoglobin were achieved compared with epoetin alfa in ESA-naive patients with lower-risk myelodysplastic syndromes. Long-term follow-up and additional data will be needed to confirm these results and further refine findings in other subgroups of patients with lower-risk myelodysplastic syndromes, including non-mutated SF3B1 or ring sideroblast-negative subgroups.
Celgene and Acceleron Pharma.
Venetoclax, a selective B cell leukemia/lymphoma-2 (BCL2) inhibitor, has recently shown activity in relapsed or refractory (R/R) acute myeloid leukemia (AML). Effective biomarkers for identifying ...patients most likely to respond to venetoclax-based treatment are of clinical utility. In this study, we aimed to evaluate the efficacy and safety profiles of venetoclax-based therapy in a total 40 R/R AML patients and identify the potentially predictive factors for response. Overall response rate was 50%, including 9 (22.5%) complete response (CR) or CR with incomplete hematologic recovery of either neutrophil or platelet counts (CRi). Median time to best response was 1.4 months and the median overall survival (OS) was 6.6 months. Presence of intermediate-risk cytogenetics predicted better OS compared to unfavorable-risk cytogenetics. Patients harboring
NPM1
,
RUNX1
, or
SRSF2
mutations seemed to have higher CR/CRi rates and median OS was significantly longer in
RUNX1
-mutated patients. On the contrary, patients with
FLT3
-ITD,
TP53
, or
DNMT3A
mutations did not reach any objective response and had worse OS. No laboratory or clinical tumor lysis syndrome was observed and the most common adverse events were prolonged cytopenias which resulted in 67.5% of febrile neutropenia. Patients with concurrent use of azole antifungals had similar incidence of cytopenias compared with those without azole antifungals. In summary, we demonstrate that venetoclax is an effective and well-tolerated salvage option for R/R AML patients. Survival benefits were particularly remarkable in patients with intermediate-risk cytogenetics or
RUNX1
mutations. In contrast,
TP53
,
NRAS
, and
DNMT3A
mutations as well as
FLT3
-ITD conferred negative impact on survival.
Summary
Leukaemic stem cell (LSC) gene expression has recently been linked to prognosis in patients with acute myeloid leukaemia (17‐gene LSC score, LSC‐17) and myelodysplastic syndromes. Although ...chronic myelomonocytic leukaemia (CMML) is regarded as a stem cell disorder, the clinical and biological impact of LSCs on CMML patients remains elusive. Making use of multiple independent validation cohorts, we here describe a concise three‐gene expression signature (LSC‐3, derived from the LSC‐17 score) as an independent and robust prognostic factor for leukaemia‐free and overall survival in CMML. We propose that LSC‐3 could be used to supplement existing risk stratification systems, to improve prognostic performance and guide management decisions.
The present study evaluated the psychometric properties of four instruments related to internet use, namely the Bergen Social Media Addiction Scale (BSMAS), Smartphone Application-Based Addiction ...Scale (SABAS), (nine-item) Internet Gaming Disorder Scale Short Form (IGDS9-SF), and Nomophobia Questionnaire (NMPQ) as well as their associations with psychological distress among Malaysian university students. A total of 380 Malaysian university students (71.6% females, mean age 24.0 years) were recruited through convenience sampling and completed an online survey including questions concerning socio-demographic background, social media addiction, smartphone addiction, internet gaming disorder, and nomophobia. Confirmatory factor analysis and Rasch analysis were applied to evaluate the psychometric properties of the instruments and Cronbach's alpha value and McDonald's omega value were used to confirm the internal consistency reliability of the instruments. The unidimensional structure was confirmed for the BSMAS, SABAS, and IGDS9-SF while the four-factor structure was confirmed for NMPQ. All instruments showed good internal consistency reliability. Promising validity and reliability were confirmed for BSMAS, SABAS, IGDS9-SF, and NMPQ. Therefore, they are useful to assess different types of problematic internet use among university students in Malaysia. Furthermore, a significant association was observed between internet use and psychological distress. The present study is the first to investigate the validity and reliability of BSMAS, SABAS, IGDS9-SF, and NMPQ among Malaysian university students using rigorous psychometric testing methods (i.e., Rasch analysis).
Summary
Increasing evidence supports the role of the immune microenvironment and associated signalling in the pathogenesis of myelodysplastic syndromes (MDS). Nevertheless, the clinical relevancy of ...immune signals in patients with MDS remains elusive. To address this, we used single‐sample gene‐set enrichment analysis to score immune signatures of bone marrow (BM) samples from 176 patients with primary MDS. Enhanced signatures of ‘immature dendritic cells’ and ‘natural killer cells with cluster of differentiation (CD)56bright’ were correlated with better overall survival (OS), whilst higher ‘CD103+ signature’ was associated with reduced survival. An MDS‐Immune‐Risk (MIR) scoring system was constructed based on the weighted sums derived from Cox regression analysis. High MIR scores were correlated with higher revised International Prognostic Scoring System (IPSS‐R) scores and mutations in ASXL transcriptional regulator 1 (ASXL1), Runt‐related transcription factor 1 (RUNX1), and tumour protein p53 (TP53). High‐score patients had significantly inferior leukaemia‐free survival (LFS) and OS than low‐score patients. The prognostic significance of MIR scores for survival remained valid across IPSS‐R subgroups and was validated in two independent cohorts. Multivariable analysis revealed that a higher MIR score was an independent adverse risk factor for LFS and OS. We further proposed a model with the combination of MIR score and gene mutations to be complementary to IPSS‐R for the prognostication of LFS and OS of patients with MDS.
Safe and effective prophylactic vaccines are urgently needed to contain the coronavirus disease 2019 (COVID-19) pandemic. However, several vaccination-related adverse effects have been reported. ...Here, we report a rare case of severe immune thrombocytopenia occurring 3 days after receiving the mRNA-1273 (Moderna) COVID-19 vaccine in an Asian woman with a history of refractory lung adenocarcinoma treated with durvalumab, an immune checkpoint inhibitor. Treatment with platelet transfusion (12 units) and oral prednisolone (1 mg/kg per day) significantly improved her hemoptysis with thrombocytopenia. To the best of our knowledge, this is the first case of ITP following Moderna inoculation among Asians. This study highlights a potential adverse effect of mRNA-based COVID-19 vaccines in cancer patients receiving immune checkpoint inhibitors.
Aberrant alternative splicing (AS) is involved in leukemogenesis. This study explored the clinical impact of alterations in global AS patterns in 341 patients with acute myeloid leukemia (AML) newly ...diagnosed at the National Taiwan University Hospital and validated it using The Cancer Genome Atlas (TCGA) cohort. While studying normal cord blood CD34+/CD38− cells, we found that AML cells exhibited significantly different global splicing patterns. AML with mutated TP53 had a particularly high degree of genome‐wide aberrations in the splicing patterns. Aberrance in the global splicing pattern was an independent unfavorable prognostic factor affecting the overall survival of patients with AML receiving standard intensive chemotherapy. The integration of global splicing patterns into the 2022 European LeukemiaNet risk classification could stratify AML patients into four groups with distinct prognoses in both our experimental and TCGA cohorts. We further identified four genes with AS alterations that harbored prognostic significance in both of these cohorts. Moreover, these survival‐associated AS events are involved in several important cellular processes that might be associated with poor response to intensive chemotherapy. In summary, our study demonstrated the clinical and biological implications of differential global splicing patterns in AML patients. Further studies with larger prospective cohorts are required to confirm these findings.
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal myeloid malignancies. Though several recurrent mutations are closely correlated with clinical outcomes, data concerning the ...association between mutation variant allele frequencies (VAF) and prognosis are limited. In this study, we performed comprehensive VAF analyses of relevant myeloid‐malignancy related mutations in 698 MDS patients and correlated the results with their prognosis. Mutation VAF in DNMT3A, TET2, ASXL1, EZH2, SETBP1, BCOR, SFSF2, ZRSR2, and TP53 mutations correlated with outcomes. In multivariable analysis, DNMT3A and ZRSR2 mutations with high VAF and mutant IDH2, CBL, U2AF1, and TP53 were independent poor prognostic factors for overall survival. A substantial portion of patients in each revised International Prognostic Scoring System (IPSS‐R) risk group could be adjusted to different prognostic groups based on the integrated VAF and mutational profiles. Patients with these unfavorable mutations in each IPSS‐R risk subgroup had survivals worse than other patients of the same risk but similar to those in the next higher‐risk subgroup. Furthermore, patients harboring U2AF1 mutation might benefit from hypomethylating agents. This study demonstrated the critical role of VAF of mutations for risk stratification in MDS patients and may be incorporated in novel scoring systems.
