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Introduction: Talquetamab, a bispecific antibody targeting GPRC5D × CD3, is approved for the treatment of patients with triple-class -exposed (TCE) relapsed/refractory multiple myeloma (RRMM) on the basis of the results from the phase I/II MonumenTAL-1 trial. The relative effectiveness of talquetamab vs. real-world physician's choice of therapy (RWPC) was assessed using adjusted comparisons. Methods: An external control arm for MonumenTAL-1 (subcutaneously administered talquetamab 0.4 mg/kg weekly [QW] and 0.8 mg/kg every other week [Q2W]) was created from two observational real-world studies: LocoMMotion and MoMMent. Imbalances in baseline covariates were adjusted using inverse probability weighting. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), ≥ very good partial response (VGPR), and ≥ complete response (CR); odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional hazards model. Results: After reweighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, patients treated with talquetamab QW (n = 143) had significantly improved outcomes vs. RWPC; RRs were ORR 2.67, p < 0.0001; ≥ VGPR 4.70, p < 0.0001; ≥ CR 78.05, p = 0.0002; and HRs were PFS 0.52, p < 0.0001; TTNT 0.48, p < 0.0001; OS 0.36, p < 0.0001. Patients treated with talquetamab Q2W (n = 145) also had significantly improved outcomes vs. RWPC; RRs were ORR 2.62, p < 0.0001; ≥ VGPR 5.04, p < 0.0001; ≥ CR 101.14, p = 0.0002; and HRs were PFS 0.40, p < 0.0001; TTNT 0.39, p < 0.0001; OS 0.37, p < 0.0001. Conclusion: Effectiveness of talquetamab for both schedules was significantly better than RWPC for ORR, ≥ VGPR, ≥ CR, PFS, OS, and TTNT, highlighting its clinical benefit for patients with TCE RRMM. Trial Registration: MonumenTAL-1, ClinicalTrials.gov identifier NCT03399799/NCT04634552; LocoMMotion, ClinicalTrials.gov identifier NCT04035226; MoMMent, ClinicalTrials.gov identifier NCT05160584. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a genetically complex and heterogenous malignancy with a 5-year survival rate of approximately 60%. Despite advances in therapy, patients experience cycles of remission and relapse, with each successive line of therapy associated with poorer outcomes; therefore, therapies with different mechanisms of action against new myeloma antigens are needed. G protein–coupled receptor class C group 5 member D (GPRC5D) has emerged as a novel therapeutic target for the treatment of multiple myeloma. We review the biology and target validation of GPRC5D, and clinical data from early phase trials of GPRC5D-targeting bispecific antibodies, talquetamab and forimtamig, and chimeric antigen receptor T cell (CAR-T) therapies, MCARH109, OriCAR-017, and BMS-986393. In addition to adverse events (AEs) associated with T-cell–redirection therapies irrespective of target, a consistent pattern of dermatologic and oral AEs has been reported across several trials of GPRC5D-targeting bispecific antibodies, as well as rare cerebellar events with CAR-T therapy. Additional studies are needed to understand the underlying mechanisms involved in the development of skin- and oral-related toxicities. We review the strategies that have been used to manage these GPRC5D-related toxicities. Preliminary efficacy data showed overall response rates for GPRC5D-targeting T-cell–redirecting therapies were ≥64%; most responders achieved a very good partial response or better. Pharmacokinetics/pharmacodynamics showed that these therapies led to cytokine release and T-cell activation. In conclusion, results from early phase trials of GPRC5D-targeting T-cell–redirecting agents have shown promising efficacy and manageable safety profiles, including lower infection rates compared with B-cell maturation antigen- and Fc receptor-like protein 5-targeting bispecific antibodies. Further clinical trials, including those investigating GPRC5D-targeting T-cell–redirecting agents in combination with other anti-myeloma therapies and with different treatment modalities, may help to elucidate the future optimal treatment regimen and sequence for patients with multiple myeloma and improve survival outcomes. Video Summary 6wb1VFUFJB3zLP3nqMGxNa [ABSTRACT FROM AUTHOR]

This study investigated the effect of economic vulnerability on unmet needs during the first wave of the coronavirus disease 2019 (COVID-19) epidemic in Europe among adults aged 50 years and older using data from the regular administration of the Survey of Health, Ageing and Retirement in Europe (SHARE) and the specific telephone survey administered regarding COVID-19 (SHARE Corona Survey). It addressed three main research questions: Did people who were in difficult economic situations before the epidemic face more barriers to accessing healthcare than others? If so, to what extent can these discrepancies be attributed to initial differences in health status, use of care, income or education between vulnerable individuals and non-vulnerable individuals or to differential effects of the pandemic on these groups? Did the effect of economic vulnerability with regard to unmet needs during the pandemic differ across countries? Unmet healthcare needs are characterised by three types of behaviours likely to be induced by the pandemic: forgoing care for fear of contracting COVID-19, having pre-scheduled care postponed and being unable to obtain medical appointments or treatments when needed. Our results substantiate the existence of significant differences in accessing healthcare during the pandemic according to economic vulnerability and of cumulative effects of economic and medical vulnerabilities: the impact of economic vulnerability is notably stronger among those who were in poor health before the outbreak and thus the oldest individuals. The cross-country comparison highlighted heterogeneous effects of economic vulnerability on forgoing care and having care postponed among countries, which are not comparable to the initial cross-country differences in social inequalities in access to healthcare. [ABSTRACT FROM AUTHOR]

Survival rates for children with acute myeloid leukemia (AML) exceed 60 % when modern, intensified chemotherapeutic regimens and enhanced supportive care measures are employed. Despite well-recognized improvements in outcomes, primary refractory or relapsed pediatric AML yields significant morbidity and mortality, and improved understanding of this obstinate population along with refined treatment protocols are urgently needed. Although a significant number of patients with refractory or relapsed disease will achieve remission, long-term survival rates remain poor, and efforts to identify therapies which will improve OS are under continuous investigation. The current fundamental goal of such investigation is the achievement of as complete a remission as possible without dose-limiting toxicities, and the progression to hematopoietic stem cell transplantation thereafter. In this review the scope of the problem of relapsed and refractory AML as well as current and emerging chemotherapy options will be discussed. [ABSTRACT FROM AUTHOR]