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Background Up to one third of survivors of AKI that required dialysis (AKI-D) during hospitalization remain dialysis dependent at hospital discharge. Of these, 20%–60%, depending on the clinical setting, eventually recover enough kidney function to stop dialysis, and the remainder progress to ESKD. Methods To describe the challenges facing those still receiving dialysis on discharge, the AKINow Committee conducted a group discussion comprising 59 participants, including physicians, advanced practitioners, nurses, pharmacists, and patients. The discussion was framed by a patient who described gaps in care delivery at different transition points and miscommunication between care team members and the patient. Results Group discussions collected patient perspectives of ( 1 ) being often scared and uncertain about what is happening to and around them and ( 2 ) the importance of effective and timely communication, a comfortable physical setting, and attentive and caring health care providers for a quality health care experience. Provider perspectives included ( 1 ) the recognition of the lack of evidence-based practices and quality indicators, the significant variability in current care models, and the uncertain reimbursement incentives focused on kidney recovery and ( 2 ) the urgency to address communication barriers among hospital providers and outpatient facilities. Conclusions The workgroup identified key areas for future research and policy change to ( 1 ) improve communication among hospital providers, dialysis units, and patients/care partners; ( 2 ) develop tools for risk classification, subphenotyping, and augmented clinical decision support; ( 3 ) improve education to providers, staff, and patients/care partners; ( 4 ) identify best practices to improve relevant outcomes; ( 5 ) validate quality indicators; and ( 6 ) assess the effect of social determinants of health on outcomes. We urge all stakeholders involved in the process of AKI-D care to align goals and work together to fill knowledge gaps and optimize the care to this highly vulnerable patient population.

Abstract Introduction The pivotal study of the extravascular implantable cardioverter‐defibrillator (EV ICD) recently demonstrated primary efficacy and safety endpoints comparable to previous ICD systems. Patient experience with this novel device has not been reported. The current study examined the standardized patient‐reported outcome (PRO) metrics of quality of life (QOL) and patient acceptance of the device. Methods The EV ICD Pivotal Study was a prospective, single‐arm, nonrandomized, global, premarket approval trial. Patients completed the 12‐Item Short Form Survey (SF‐12) QOL surveys at baseline and at 6 months following implant. Additionally, patients completed the Florida Patient Acceptance Survey (FPAS) QOL survey at 6 months. Results From baseline to 6 months, patients within the EV ICD Pivotal Study ( n = 247) reported statistically significant SF‐12 improvements in physical QOL (45.4 ± 9.4 vs. 46.8 ± 9.1 respectively, p = .020) and no changes in mental QOL (49.3 ± 10.4 vs. 50.5 ± 9.7, p = .061). No differences were noted by sex, atrial fibrillation, or the experience of ICD shock. EV ICD patients reported better total FPAS patient acceptance of their ICD than TV‐ICD or S‐ICD patients using historical norms comparisons (80.4 ± 15.7 vs. 70.2 ± 17.8, p < .0001 for S‐ICD and 73.0 ± 17.4, p = .004 for TV‐ICD). Conclusion The initial PROs for EV ICD patients indicated that patients had improvements in physical QOL from baseline to 6‐month follow‐up and markedly better overall acceptance of their ICD compared to a previous study with S‐ICD and TV‐ICD data. These initial results suggest that the EV ICD is evaluated positively by patients.

Introduction: Historically, older patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL) were often deemed ineligible for curative-intent autologous stem cell transplant (ASCT) due to age and concern for increased toxicity related to comorbidities. We previously demonstrated in the pivotal ZUMA-7 study that older pts with R/R LBCL can safely receive axicabtagene ciloleucel (axi-cel) as second-line (2L) therapy with improved event-free survival (EFS), response rate, and quality of life compared with standard of care (SOC) based on results from the primary EFS analysis (Westin, et al. Clin Cancer Res. 2023). At a median follow-up of 47.2 months (mo), results from the ZUMA-7 primary overall survival (OS) analysis demonstrated superior OS in the intention-to-treat (ITT) analysis (hazard ratio [HR], 0.73; 95% CI, 0.54-0.98; stratified two-sided log-rank P=0.03; Westin, et al. N Engl J Med. 2023; NCT03391466). We now report updated efficacy and safety results from the primary OS analysis among ZUMA-7 pts aged ≥65 years (y) and ≥70 y. Methods: Eligible pts were randomized 1:1 to axi-cel or SOC (2-3 cycles of platinum-based chemoimmunotherapy; responding pts proceeded to high-dose chemotherapy with ASCT). The primary OS analysis occurred 5 y after the first pt was randomized (01/25/2018) per protocol. Other endpoints included progression-free survival (PFS) per investigator assessment and safety. A planned subgroup analysis of pts aged ≥65 y was conducted in addition to an analysis for those ≥70 y. Multivariate analyses were performed to examine treatment efficacy with axi-cel compared with SOC after adjusting for multiple covariates, including sex, disease type, molecular subgroup, lactate dehydrogenase (LDH), tumor burden, and age; strata for these analyses included second-line age-adjusted International Prognostic Index (aaIPI), and relapsed vs refractory disease. Exploratory analyses were conducted to determine the association between OS and axi-cel product characteristics for pts aged ≥65 y. Results: A total of 109 pts were included in the analysis (axi-cel: 51 were ≥65 y, 26 of whom were ≥70 y, maximum age was 80 y; SOC: 58 were ≥65 y, 27 of whom were ≥70 y, maximum age was 81 y). Compared with SOC pts at baseline, more axi-cel pts had high-risk features, including aaIPI 2-3, elevated LDH, and high-grade B-cell lymphoma. At a median follow-up of 46.6 mo, OS was prolonged in the axicel vs SOC arm in pts aged ≥65 y (HR, 0.691; 95% CI, 0.401-1.190) and for those ≥70 y (HR, 0.330; 95% CI, 0.135-0.809). Similar results were observed using the piecewise Cox regression model. The median OS for axi-cel and SOC pts was 43.5 mo (95% CI, 20.9-not estimable [NE]) and 19.6 mo (95% CI, 12.3-NE), respectively, among those aged ≥65 y, and 24.7 mo (95% CI, 12.8-NE) and 11.2 mo (95% CI, 6.1-NE), respectively, among those aged ≥70 y. In the SOC arm, 57% and 52% of pts received subsequent cellular immunotherapy off protocol in pts aged ≥65 y and ≥70 y, respectively. Multivariate analyses demonstrated an even greater OS benefit with axi-cel over SOC when adjusting for differences in baseline characteristics in pts aged ≥65 y (HR, 0.526; 95% CI, 0.266-1.041) and in pts aged ≥70 y (HR, 0.184; 95% CI, 0.045-0.755). PFS assessed by investigator confirmed benefit of axi-cel over SOC in pts aged ≥65 y (HR, 0.406; 95% CI, 0.230-0.715) and in pts aged ≥70 y (HR, 0.206; 95% CI, 0.078-0.547). The median PFS for axi-cel and SOC pts was 28.7 mo (95% CI, 5.1-NE) and 5.0 mo (95% CI, 2.8-7.2), respectively, for those aged ≥65 y, and 11.4 mo (95% CI, 4.1-NE) and 2.7 mo (95% CI, 1.7-5.0), respectively, for those aged ≥70 y. No new treatment-related deaths occurred since the primary EFS analysis. There were no manufacturing failures for any pt who underwent leukapheresis. Similar associations between product characteristics and outcomes were observed among the elderly and overall populations, including improved OS associated with a greater (&gt;median) proportion of juvenile or stem memory T-cell phenotype cells (CCR7+CD45RA+ T cells) in the axi-cel product among pts aged ≥65 y (HR, 0.369; 95% CI, 0.138-0.984). Conclusion: Axi-cel as 2L therapy prolonged survival over SOC in pts aged ≥65 y, including in pts aged ≥70 y. These findings confirm that age alone should not be a barrier for consideration of CAR T-cell therapy, supporting the use of axi-cel as a curative-intent 2L therapeutic option for older pts with R/R LBCL.

Introduction Relapsed/refractory multiple myeloma (RRMM) is a hematologic cancer associated with no current widely-accepted cure, cycles of relapse and remission, treatment resistance, and high morbidity and mortality, which necessitate new treatments and therapeutic targets. 1-3 Innovative therapies that target BCMA, CD38, GPRC5D, FcRH5, and others in the RRMM development pipeline are recently approved or under investigation, but real-world evidence on clinician perceptions of emerging trends and unmet needs remains limited. A Delphi panel was conducted with US clinicians to evaluate the level of unmet need and treatment decisions among patients with RRMM who are triple-class-exposed (TCE). Methods This double-blinded study consisted of two phases: a web survey (phase 1) and a Delphi panel (phase 2). A targeted literature review was conducted first to understand unmet needs and treatment decisions associated with management of RRMM in the US and inform the development of primary research materials. The web survey was completed by 21 US clinicians. Survey findings were then used to inform the phase 2 Delphi panel, a systematic, validated approach to gain consensus. This consisted of two iterative rounds of a question answered by nine experts selected from participants in the web survey. Consensus on a question was defined as at least 70% agreement. The double-blinded panel was conducted via the Microsoft Teams platform, and poll questions were administered through Vevox. Responses were blinded to preserve respondents' anonymity and participants were also blinded to the study sponsor. Results Overall, consensus was reached that despite recent improvement in treatment landscape, there is still a high level of unmet need for patients with RRMM who are TCE (89% of participants). More specifically, consensus was reached (89%) that the top three areas of unmet need were treatment resistance, guidance on treatment sequencing, and novel mechanisms of action (MoAs) and targets (Figure 1). Unmet need is also particularly pronounced for certain patient subgroups, with 89% and 78% of participants agreeing that patients who are functionally high-risk and penta-refractory, respectively, experience the greatest unmet need. When asked about which novel therapies would be most promising for addressing the unmet needs, participants agreed that the top 4 therapeutic targets are GPCR5D (95%), BCMA (81%), FcRH5 (81%), and BCL-2 (81%). Various factors impact treatment choice and sequencing, with most participants (78%) agreeing that treatment history is the most influential factor impacting sequencing. The panel also agreed that prior toxicity (grade 3-4 AEs, 89%) and convenience of dosing frequency (78%), respectively, most impact dosing decisions. All agreed there is a need for resources to manage some AEs, particularly newer AEs (like skin and nail effects) of emerging treatments. Of the AEs identified in the survey as top drivers of treatment choice, participants reached consensus on two: neurotoxicity (e.g., ICANS) (89%) and infection (100%). Conclusions In this Delphi study, consensus was reached that a high level of unmet need remains for patients with RRMM, who are TCE with unmet need varying dependent on patient subgroup and treatment history. There was consensus that additional treatment choices with novel targets/MoAs are needed. Participants agreed that AEs, toxicity, infection, and treatment history impact treatment choice and sequencing, and considerations and challenges vary by subgroup. Overall, findings from this study support that there is a need for additional treatment options with novel MoAs/therapeutic targets that address priority unmet needs for patients with RRMM, who are TCE. References 1. Gonsalves W et al. The next generation of novel therapies for the management of relapsed multiple myeloma. Future Oncol (London, England). 2017;13(1):63-75. https://doi.org/10.2217/fon-2016-0200 2. Braunstein M et al. A new decade: novel immunotherapies on the horizon for relapsed/refractory multiple myeloma. Expert Rev Hematol. 2022;14(4):377-389. doi:10.1080/17474086.2021.1909469 3. Bruno AS et al. Recent real-world treatment patterns and outcomes in US patients with relapsed/refractory multiple myeloma. Expert Rev Hematol. 2020;13(9):1017-1025. doi:10.1080/17474086.2020.1800451

Background: Despite the efficacy of covalent (c) Bruton tyrosine kinase inhibitors (BTKi) in R/R MCL, disease relapse arises through evolution of resistance mechanisms or development of cBTKi intolerance. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi has favorable oral pharmacology that enables continuous BTK inhibition throughout the daily dosing interval regardless of the intrinsic rate of BTK turnover. Pirtobrutinib is the first BTKi to demonstrate durable efficacy following prior cBTKi therapy in heavily pre-treated R/R MCL and was well-tolerated with a low frequency of treatment discontinuation due to toxicity (Wang et al., JCO, 2023). Pirtobrutinib is approved in the USA to treat relapsed or refractory MCL after at least two lines of systemic therapy including a prior cBTKi. Here, we report updated results of pirtobrutinib therapy in all patients (pts), including those with biologically high-risk R/R MCL with a median survival follow-up of 24.2 months (range, 18.2-29.8). Methods: Pts with R/R MCL received pirtobrutinib monotherapy in the multicenter Phase 1/2 BRUIN trial (NCT03740529). Efficacy was assessed in all cBTKi pre-treated pts, as well as in cBTKi treatment-naïve pts. Key endpoints included overall response rate (ORR) as assessed by independent review committee per Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Pts were included across the dose escalation range and expansion (25-300 mg/day) with 93% (n=141) receiving at least one dose of 200 mg/day, the FDA-approved dose. A data cut of 05 May 2023 was utilized. Results: Among all 152 pts with R/R MCL who received a prior cBTKi, the median age was 70 years (range, 46-88), and 52% had intermediate-risk and 28.3% had high-risk sMIPI scores. Median prior lines of therapy were 3 (range, 1-9), including an anti-CD20 antibody (96.7%), chemotherapy (90.1%), immunomodulator (17.1%), stem cell transplant (21.7%), BCL-2 inhibitor (15.8%), CAR-T cell therapy (8.6%), and PI3K inhibitor (3.9%). Among pts with high-risk biomarker data available, 30/60 (50%) had TP53 mutations and 45/63 (71%) had a Ki-67 index of ≥30%. The ORR for cBTKi pre-treated pts was 49.3% (95% CI, 41.1-57.6), including 15.8% complete responses (n=24) and 33.6% partial responses (n=51), whilst cBTKi naïve pts (n=14) had an ORR of 85.7% (95% CI, 57.2-98.2). The ORR among 128 pts who had discontinued a prior cBTKi due to PD and 21 pts who had discontinued for toxicity/other reasons was 43.0% and 90.5%, respectively. Among the 75 responding cBTKi pre-treated pts, the median DOR was 21.6 months (95% CI, 9.2-27.2) at a median follow-up of 24 months. The 18- and 24-month DOR rates were 51.9% (95% CI, 37-64.8) and 38.9% (95% CI, 22.7-54.8), respectively. ORR and DOR by high-risk subgroups (including blastoid/pleomorphic variants, Ki-67 index ≥30%, and TP53 mutations) are shown in Table 1. The 18- and 24-month DOR rates among 12 responding cBTKi naïve pts were both 90.0% (95% CI, 47.3-98.5). The median PFS and OS for cBTKi pre-treated pts was 5.6 months (95% CI, 5.3-9.2), and 23.5 months (95% CI, 17.1-NE), respectively. In the MCL cohort (n=166), the most frequent treatment-emergent adverse events (TEAEs) were fatigue (31.9%), diarrhea (22.3%), and dyspnea (17.5%). The most common Grade ≥3 TEAE was neutropenia/neutrophil count decreased (13.3%) and the rate of Grade ≥3 infections was (19.9%). Grade ≥3 hemorrhage/hematoma (2.4%) and all-grade atrial fibrillation/flutter (3.6%) were infrequent. Overall, 8 pts (5%) had treatment-related AEs leading to dose reductions and 5 (3%) had treatment-related AEs leading to pirtobrutinib discontinuation. Conclusion: Pirtobrutinib continues to demonstrate durable efficacy and a favorable safety profile in heavily pre-treated R/R MCL pts with prior cBTKi therapy. High ORRs were observed in pts who had PD on a prior cBTKi, and in pts with high-risk disease features including blastoid/pleomorphic variants, elevated Ki-67 index, and TP53 mutations.

AbstractIntroductionThe American College of Sports Medicine provided guidelines for exercise prescriptions in cancer survivors for specific cancer‐ and treatment‐related health outcomes. However, there was insufficient evidence to generate exercise prescriptions for 10 health outcomes of cancer treatment. We sought to update the state of evidence.MethodsWe conducted a systematic review of these 10 understudied health outcomes (bone health, sleep, cardiovascular function, chemotherapy‐induced peripheral neuropathy (CIPN), cognitive function, falls and balance, nausea, pain, sexual function, and treatment tolerance) and provided an update of evidence.ResultsWhile the evidence base for each outcome has increased, there remains insufficient evidence to generate exercise prescriptions. Common limitations observed across outcomes included: variability in type and quality of outcome measurement tools, variability in definitions of the health outcomes, a lack of phase III trials, and a majority of trials investigating breast or prostate cancer survivors only.ConclusionWe identified progress in the field of exercise oncology for several understudied cancer‐ and treatment‐related health outcomes. However, we were not able to generate exercise prescriptions due to continued insufficient evidence base. More work is needed to prescribe exercise as medicine for these understudied health outcomes, and our review highlights several strategies to aid in research acceleration within these areas of exercise oncology.