Early intervention with daratumumab improves survival for patients with high-risk smouldering myeloma
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Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes
In the MAIA study, daratumumab plus lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). We report updated efficacy and safety from MAIA (median follow-up, 64.5 months), including a subgroup analysis by patient age (<70, ≥70 to <75, ≥75, and ≥80 years). Overall, 737 transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint, PFS, was improved with D-Rd versus Rd (median, 61.9 vs 34.4 months; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.45–0.67; P < 0.0001). Median OS was not reached in the D-Rd group versus 65.5 months in the Rd group (HR, 0.66; 95% CI, 0.53–0.83; P = 0.0003); estimated 60-month OS rates were 66.6% and 53.6%, respectively. D-Rd achieved higher rates of complete response or better (≥CR; 51.1% vs 30.1%), minimal residual disease (MRD) negativity (32.1% vs 11.1%), and sustained MRD negativity (≥18 months: 16.8% vs 3.3%) versus Rd (all P < 0.0001). D-Rd demonstrated clinically meaningful efficacy benefits across age groups. No new safety concerns were observed. Updated results (median follow-up, >5 years) continue to support frontline use of D-Rd in transplant-ineligible patients with NDMM.
Feasibility and efficacy of therapeutic drug monitoring of abiraterone in metastatic castration resistant prostate cancer patients
Previous studies demonstrated better outcomes for mCRPC (metastatic castration resistant prostate cancer) patients with higher abiraterone exposure (minimal plasma concentration (Cmin) > 8.4 ng/mL), but around 40% of patients experience exposure below this target. Pharmacokinetic (PK)-guided interventions following Therapeutic Drug Monitoring (TDM) could optimise exposure and outcomes. We aimed to evaluate the feasibility and effect on treatment outcomes of abiraterone TDM.
Group arts interventions for depression and anxiety among older adults: a systematic review and meta-analysis
In this systematic review and meta-analysis, we assessed the efficacy of group arts interventions, where individuals engage together in a shared artistic experience (for example, dance or painting), for reducing depression and anxiety among older adults (> 55 yr without dementia). Fifty controlled studies were identified via electronic databases searched to February 2024 (randomised: 42, non-randomised: 8). Thirty-nine studies were included. Thirty-six studies investigated the impact of group arts interventions on depression (n = 3,360) and ten studies investigated anxiety (n = 949). Subgroup analyses assessed whether participant, contextual, intervention and study characteristics moderated the intervention–outcome relationship. Risk of bias was assessed with appropriate tools (RoB-2, ROBINS-1). Group arts interventions were associated with a moderate reduction in depression (Cohen’s d = 0.70, 95% confidence interval (CI) = 0.54–0.87, P < 0.001) and a moderate reduction in anxiety (d = 0.76, 95% CI = 0.37–1.52, P < 0.001), although there was publication bias in the depression studies. After a trim and fill adjustment, the effect for depression remained (d = 0.42; CI = 0.35–0.50; P < 0.001). Context moderated this effect: There was a greater reduction in depression when group arts interventions were delivered in care homes (d = 1.07, 95% CI = 0.72–1.42, P < 0.001) relative to the community (d = 0.51, 95% CI = 0.32–0.70, P < 0.001). Findings indicate that group arts are an effective intervention for addressing depression and anxiety among older adults.
Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group
Given the heterogeneity of acute myeloid leukemia patients, it is necessary to identify patients considered fit for intensive therapy but who will perform poorly, and in whom alternative approaches deserve investigation. We analyzed 1034 fit adults ≤70 years intensively treated between 2012 and 2022 in the CETLAM group. Young adults ( ≤ 60 years) presented higher remission rates and improved survival than older adults above that age (CR 79% vs. 73%; p = 0.03 and 4-yr OS 53% vs. 33%; p < 0.001). Remission and survival outcomes varied among different genetic subsets. An especially adverse genetic group included complex, monosomal karyotype, TP53 alterations (deleted/mutated), and MECOMr. Transplant feasibility in this very adverse risk group was low, and OS and EFS at 4 years were 14% and 12%, in contrast to 70% and 57% in the favorable group and 38% and 32% in all other patients. We integrated clinical and genetic data into the Intensive Chemotherapy Score for AML (ICSA) with 6-risk categories with significantly different remission rates and OS, validated in another cohort of 581 AML patients from a previous CETLAM protocol. In summary, we identified groups of fit patients that benefit differently from an intensive approach which may be helpful in future treatment decisions.
Psychological booster shots targeting memory increase long-term resistance against misinformation
An increasing number of real-world interventions aim to preemptively protect or inoculate people against misinformation. Inoculation research has demonstrated positive effects on misinformation resilience when measured immediately after treatment via messages, games, or videos. However, very little is currently known about their long-term effectiveness and the mechanisms by which such treatment effects decay over time. We start by proposing three possible models on the mechanisms driving resistance to misinformation. We then report five pre-registered longitudinal experiments (Ntotal = 11,759) that investigate the effectiveness of psychological inoculation interventions over time as well as their underlying mechanisms. We find that text-based and video-based inoculation interventions can remain effective for one month—whereas game-based interventions appear to decay more rapidly—and that memory-enhancing booster interventions can enhance the diminishing effects of counter-misinformation interventions. Finally, we propose an integrated memory-motivation model, concluding that misinformation researchers would benefit from integrating knowledge from the cognitive science of memory to design better psychological interventions that can counter misinformation durably over time and at-scale.
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