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Introduction: Although daratumumab-containing regimens improve multiple myeloma (MM) outcomes, recurrence is inevitable., Methods and Objective: We performed a retrospective study using the Canadian Myeloma Research Group Database to benchmark the efficacy of carfilzomib- or pomalidomide-based therapies immediately following progression on daratumumab treatment., Results: We identified 178 such patients; median number of prior lines of therapy was 3, 97% triple-class exposed, and 60% triple-class refractory. In our cohort, 75 received a subsequent carfilzomib-based therapy, 79 received a pomalidomide-based therapy, and 24 received a treatment with both immunomodulatory drug (IMiD) and proteasome inhibitor (PI) using carfilzomib and/or pomalidomide. The median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 4.5 and 14.2 months, respectively. Carfilzomib-based therapy yielded a median PFS and OS of 4.5 and 10.2 months, respectively, compared to 5.2 and 21.7 months for pomalidomide-based therapy. Patients who received both IMiD and PI with carfilzomib and/or pomalidomide had a median PFS and OS of 4.1 and 14.5 months, respectively., Conclusion: Our observations demonstrate the poor outcome of MM patients when standard regimens based on carfilzomib and/or pomalidomide are utilized directly after daratumumab-based therapy given in the relapsed setting. Novel therapies, including immune therapies, are urgently needed to improve the outcomes of these daratumumab-exposed patients., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology., Methods: We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding., Results: Out of 16 487 screened publications, 1612 studies were included, primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019 and 2022, compared to 384 from 2000 to 2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%)., Conclusions: This study demonstrates the rapidly growing use of post hoc subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies., (© The Author(s) 2023. Published by Oxford University Press.)

Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.3%. The median PFS and OS for patients given a single ASCT were 35.4 and 126 months. Those receiving a second induction regimen had significantly inferior outcomes, although when maintenance was used, results were comparable regardless of the number of induction regimens administered (median PFS 55.3 vs 51.1 months [p = 0.11]; median OS 158.6 vs not yet reached [p = 0.13]). Consolidation patients had a longer median PFS (55.3 vs 34.4 months [p = 0.001]), but no significant gain in median OS (p = 0.065). Patients who received lenalidomide-based maintenance experienced a median PFS of 53.7 months and OS of 159 months. In the multivariable analysis, use of any type of maintenance therapy vs no maintenance was associated with a lower risk of progression (HR 0.52 (95% CI 0.47-0.57)) and death (HR 0.58 (95% CI 0.51-0.67)). This real-world study demonstrates that, overall, first-line treatment sequence in transplant-eligible patients produces a median OS of ≥10 years. It also highlights the contribution of post-ASCT maintenance, particularly lenalidomide given until progression., (© 2023. Springer Nature Limited.)

Competing Interests: Conflict of Interest The authors have no relevant financial or non-financial interests to disclose.

Purpose: The purpose of this study was to apply both the fragility index (FI) and fragility quotient (FQ) to evaluate the degree of statistical fragility in the distal femur fracture (DFF) literature. We hypothesized that the dichotomous outcomes within the DFF literature are statistically fragile., Methods: Using preferred reporting items for systematic reviews and meta-analyses, we performed a PubMed search for distal femur fractures clinical trials from 2000 to 2022 reporting dichotomous outcomes. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ., Results: Of the 4258 articles screened, 92 met the search criteria, with eleven RCTs included for analysis. Ninety eight outcome events with 25 significant (P < 0.05) outcomes and 73 nonsignificant (P > 0.05) outcomes were identified. The overall FI and FQ for all 98 outcomes were 5 (IQR 4-6) and 0.130 (IQR 0.087-0.174), respectively. Three studies (33.3%) reported loss to follow (LTF) greater than 5., Conclusions: The randomized controlled trials in the peer-reviewed distal femur fracture literature may not be as robust as previously thought, as incorporating statistical analyses solely on a P value threshold is misleading. Standardized reporting of the P value, FI and FQ can help the clinician reliably draw conclusions based on the fragility of outcome measures., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of patients not receiving subsequent therapy is useful for MM stakeholders. We performed an analysis of attrition rates in a large disease-specific database of patients with newly diagnosed MM who received at least one line of therapy between Jan 1/10-Dec 31/20. Attrition was defined as failure to receive a subsequent line of therapy despite progression of MM or due to death. A total of 5548 patients were identified, 3111 autologous stem cell transplant (ASCT) patients and 2437 non-ASCT. In the ASCT cohort, the attrition rate was 7% after line 1, 12% after line 2, and 23% after line 3. In non-ASCT patients, the attrition rate was 19% after line 1, 26% after line 2, and 40% after line 3. Death was the dominant contributor to attrition across all cohorts, with a minority of patients alive with progressive disease in the absence of further therapy at each line. Multivariable analysis identified older age, shorter time to progression, and inferior response as independent risk factors for attrition. Our data show that attrition rates increase with each line of therapy and are higher in non-ASCT patients but are appreciably lower than previously reported. This study supports a revision of the previous definition of attrition, demonstrating that most patients who do not receive subsequent therapy are either continuing their current therapy and/or are in remission off-treatment rather than being irreversibly lost to attrition., (© 2023. The Author(s).)

Background: Lenalidomide maintenance after autologous stem cell transplant (ASCT) in multiple myeloma (MM) results in superior progression-free survival and overall survival. However, patients with high-risk multiple myeloma (HRMM) do not derive the same survival benefit from lenalidomide maintenance compared with standard-risk patients. The authors sought to determine the outcomes of bortezomib-based maintenance compared with lenalidomide maintenance in patients with HRMM undergoing ASCT., Methods: In total, the authors identified 503 patients with HRMM who were undergoing ASCT within 12 months of diagnosis from January 2013 to December 2018 after receiving triplet novel-agent induction in the Center for International Blood and Marrow Transplant Research database. HRMM was defined as deletion 17p, t(14;16), t(4;14), t(14;20), or chromosome 1q gain., Results: Three hundred fifty-seven patients (67%) received lenalidomide alone, and 146 (33%) received bortezomib-based maintenance (with bortezomib alone in 58%). Patients in the bortezomib-based maintenance group were more likely to harbor two or more high-risk abnormalities and International Staging System stage III disease (30% vs. 22%; p = .01) compared with the lenalidomide group (24% vs. 15%; p < .01). Patients who were receiving lenalidomide maintenance had superior progression-free survival at 2 years compared with those who were receiving either bortezomib monotherapy or combination therapy (75% vs. 63%; p = .009). Overall survival at 2 years was also superior in the lenalidomide group (93% vs. 84%; p = .001)., Conclusions: No superior outcomes were observed in patients with HRMM who received bortezomib monotherapy or (to a lesser extent) in those who received bortezomib in combination as maintenance compared with lenalidomide alone. Until prospective data from randomized clinical trials are available, post-transplant therapy should be tailored to each patient with consideration for treating patients in clinical trials that target novel therapeutic strategies for HRMM, and lenalidomide should remain a cornerstone of treatment., (© 2023 American Cancer Society.)

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit conferred by invasive cardiac interventions; the periprocedural considerations; the contemporary survival expectations of patients across several types of active, advanced malignancy; and the literature on cardiovascular interventions in these populations. Our objective is to develop a rational framework to guide clinical recommendations on the use of invasive cardiac interventions in patients with active, advanced cancer., Competing Interests: Dr Leong has received speaking or consulting fees from Abbvie, Ferring Pharmaceuticals, Myovant Sciences, Janssen, Novartis, Tolmar, AstraZeneca, and Paladin; and has received a research grant from Novartis. Dr Ellis has received speaking or advisory board fees from AstraZeneca, Pfizer, Takeda, Lilly, BMS, Merck, Sanofi, Janssen, Jazz, and Novartis. Dr Healey has received speaking or consulting fees from Bayer, BMS/Pfizer, Boston Scientific, and Servier; and has received research grants from Medtronic, Boston Scientific, BMS/Pfizer, and Novartis. Dr Khalaf has received consulting fees or honoraria from Paladin, Pfizer, Astellas, Jazz, and Taiho. Dr Jolly has received honoraria from Penumbra and Teleflex; and has received institutional grants from Boston Scientific. Dr Dent has received honoraria from AstraZeneca and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n = 3948). At a median follow-up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (hazard ratio [HR] 2.62, P < .001 and HR 5.01, P < .001, respectively) and OS (HR 3.85, P < .001 and HR 8.13, P < .001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% vs 30% and 53% vs 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in patients with MM and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Abiraterone and enzalutamide are treatments for metastatic castration-resistant prostate cancer (mCRPC). Due to a lack of head-to-head trials, they are prescribed interchangeably. However, the drugs have different pharmacokinetics and thus may have differing efficacy and adverse effects influenced by patient functional status and comorbid diseases. Additionally, mCRPC mainly affects older adults and since the prevalence of frailty increases with age, frailty is an important patient factor to consider in personalizing drug selection., Materials and Methods: We conducted a retrospective observational study of US veterans treated with abiraterone or enzalutamide for mCRPC from September 2014 to June 2017. Frailty was assessed using the Veterans Affairs Frailty Index (VA-FI), which utilizes administrative codes to assign a standardized frailty score. Patients were categorized as frail if VA-FI scores were > 0.2. The primary outcome was difference in overall survival (OS) between the two treatment groups. Cox regression modeling and propensity score matching was used to compare between abiraterone and enzalutamide treatments., Results: We identified 5,822 veterans, 57% of whom were initially treated with abiraterone and 43% with enzalutamide. Frail patients (n = 2,314; 39.7%) were older, with a mean age of 76.1 versus 74.9 years in the non-frail group (n = 3,508; 60.3%, p < 0.001) and had shorter OS compared to non-frail patients regardless of treatment group (18.5 vs. 26.6 months, p < 0.001). Among non-frail patients there was no significant difference in OS between abiraterone and enzalutamide treatment (27.7 vs 26.1 months, p = 0.07). However, frail patients treated with enzalutamide versus abiraterone had improved OS (20.7 vs 17.2 months, p < 0.001). In a propensity score matched analysis of frail patients (n = 2,070), enzalutamide was associated with greater median OS (24.1 vs 20.9 months, p < 0.001). In patients with dementia, enzalutamide was associated with longer OS (19.4 vs. 16.6 months, p = 0.003)., Discussion: In this study of 5822 US veterans with mCRPC, treatment with enzalutamide was associated with improved OS compared to abiraterone among frail veterans and veterans with dementia, but not among non-frail veterans. Future studies should evaluate interactions between frailty and cancer treatments to optimize selection of therapy among frail adults., Competing Interests: Declaration of Competing Interest Tanya M. Wildes reports consulting fees from Sanofi, Carevive Systems, and grants from Janssen. Hira Mian reports honoraria and consulting fees from Janssen, GlaxoSmithKline, Pfizer, Sanofi, Takeda, Amgen, and Abbvie. Martin W. Schoen reports an honorarium from Pfizer for a lecture on Real-World Data in Oncology., (Published by Elsevier Ltd.)

Multiple myeloma (MM) is a cancer of older adults and those who are more frail are at high risk of poor outcomes. Current tools for identifying and categorizing frail patients are often static and measured only at the time of diagnosis. The concept of dynamic frailty (i.e. frailty changing over time) is largely unexplored in MM. In our study, adults with newly-diagnosed MM who received novel drugs between the years 2007-2014 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Using a previously published cumulative deficit approach, a frailty index score was calculated at diagnosis and each landmark interval (1-yr, 2-yr, 3-yr post diagnosis). The association of frailty with overall survival (OS) both at baseline and at each landmark interval as well as factors associated with worsening frailty status over time were evaluated. Overall, 4617 patients were included. At baseline, 39% of the patients were categorized as moderately frail or severely frail. Among those who had 3 years of follow-up, frailty categorization changed post diagnosis in 93% of the cohort (78% improved and 72% deteriorated at least at one time point during the follow up period). In a landmark analysis, the predictive ability of frailty at the time of diagnosis decreased over time for OS (Harrell's C Statistic 0.65 at diagnosis, 0.63 at 1-yr, 0.62 at 2-yr, and 0.60 at 3-yr) and was inferior compared to current frailty status at each landmark interval. Our study is one of the first to demonstrate the dynamic nature of frailty among older adults with MM. Frailty may improve or deteriorate over time. Current frailty status is a better predictor of outcomes than frailty status at time of diagnosis, indicating the need for re-measurement in this high-risk patient population., (© 2023. The Author(s).)

Early-stage Hodgkin lymphoma has become one of the most curable hematologic malignancies. Depending upon the disease location, possible toxicities, and patient preference, chemotherapy alone with ABVD remains an accepted treatment modality for this disease. There remains a paucity of data regarding the longitudinal trajectory of health-related quality of life (HRQoL) in patients treated for HL. The impact of disease and treatment on HRQoL is increasingly important to understand as the number of long-term survivors increases. We report the longitudinal HRQoL using data prospectively collected from diagnosis up to 10 years post-treatment in the ABVD arm of the HD.6 randomized controlled trial for early-stage HL patients (N=169). We analyzed HRQoL using the EORTC QLQ-C30 collected at baseline, 3 months, 6 months, and 12 months after completion of chemotherapy and yearly up to year 10. Clinically and statistically significant improvements were noted for specific domains including emotional (3 months post-treatment), social (12 months post-treatment) and financial functioning (2 years post-treatment), and the specific symptom of fatigue (6 months post-treatment) during the follow-up period. To our knowledge, this is the first prospective, longitudinal analysis of HRQoL specifically among patients with early-stage HL treated with ABVD therapy alone. Although improvements were noted, sustained clinically and statistically significant improvements were noted only in select symptoms emphasizing the need to better understand and optimize HRQoL among this patient group., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The purpose of this study was to apply both the fragility index (FI) and fragility quotient (FQ) to evaluate the degree of statistical fragility in the distal fibular fracture (DFF) literature. We hypothesized that the dichotomous outcomes within the DFF literature are statistically fragile., Methods: We performed a PubMed search for distal fibular fractures clinical trials from 2000 to 2022 reporting dichotomous outcomes. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ., Results: Of the 1158 articles screened, 23 met the search criteria, with six RCTs included for analysis. Forty-five outcome events with 5 significant (p < 0.05) outcomes and 40 nonsignificant (p ≥ 0.05) outcomes were identified. The overall FI and FQ was 5 (IQR 4-6) and 0.089 (IQR 0.061-0.107), respectively., Conclusions: The randomized controlled trials in the peer-reviewed distal fibular fracture literature may not be as robust as previously thought, as incorporating statistical analyses solely on a P value threshold is misleading. Standardized reporting of the P value, FI and FQ can help the clinician reliably draw conclusions based on the fragility of outcome measures., Competing Interests: Declaration of Competing Interest Hassan Mian: None; Michael Megafu: None; Emmanuel Megafu: None; Sulabh Singhal: None; Nicholas Richardson, MD: None; Paul Tornetta III, MD: Paul Tornetta III, MD reports relationship with Journal of Orthopedic Trauma: Editorial Board and Governing Board. Paul Tornetta III, MD reports relationship with Wolters Kluwer Health: publishing royalties, financial and material support. Paul Tornetta III, MD reports relationship with Lippencott Williams & Wilkins: Publishing royalties. Paul Tornetta III, MD reports relationship with Smith & Nephew: royalties.; Robert L. Parisien MD: Robert L. Parisien, MD reports a relationship with American Orthopaedic Society for Sports Medicine that includes: board membership. Robert L. Parisien, MD reports a relationship with American Orthopaedic Society for Sports Medicine that includes: non-financial support. Robert L. Parisien, MD reports a relationship with Arthroscopy Association of North America that includes: non-financial support. Robert L. Parisien, MD reports a relationship with The Society of Military Orthopaedic Surgeons that includes: non-financial support. Robert L. Parisien, MD reports a relationship with Journal of Cartilage & Joint Preservation that includes: non-financial support. Robert L. Parisien, MD reports a relationship with Arthroscopy that includes: board membership. Robert L. Parisien, MD reports a relationship with Arthroscopy, Sports Medicine and Rehabilitation that includes: board membership. Robert L. Parisien, MD reports a relationship with Journal of Sport Rehabilitation that includes: board membership. Robert L. Parisien, MD reports a relationship with Arthrex Inc that includes: funding grants., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Using the Canadian Myeloma Research Group Database, a retrospective study of 167 newly diagnosed, transplant-ineligible patients with multiple myeloma (MM) that received lenalidomide-dexamethasone as front-line treatment was conducted to understand the impact of lenalidomide dosing. Starting dose modifications were common, 42% of patients started on lenalidomide <25 mg with normal renal function. During treatment course, 35% of patients required further dose reduction. Dose reductions in the first year did not have an impact on progression free survival or overall survival. Further studies need to be conducted to understand the impact of dosing strategies of anti-MM agents in the real world., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: A utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM., Methods: A qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis., Results: Eighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with their treatment decision with "trust in their oncologist" and "wanting the best treatment" as the most important to proceed with ASCT. "Afraid of side effects" was the most common reason for declining ASCT. Fifteen oncologists completed the survey and 10 follow-up interviews were conducted. Most relied on the 'eye-ball' test for ASCT eligibility over geriatric screening tools. The lack of both high-quality evidence and local guidelines impacted decision-making. Both oncologists and patients felt that chronological age alone should not affect ASCT eligibility., Conclusion: While decision-making factors regarding ASCT can be variable, both oncologists and patients indicated that chronological age alone should not represent a barrier for ASCT among older adults. Future simplification and incorporation of ASCT eligibility geriatric assessment tools in studies as well as the inclusion of these tools in local guidelines may further improve ASCT decision-making., Competing Interests: AM received consultancy/honoraria fees from Celgene, Takeda, Janssen, Amgen, Sanofi. TW received research funding from Janssen and is a consultant for Carevive Systems, Seattle Genetics and Sanofi. HM received consultancy/Honoraria fees from Celgene, Takeda, Janssen, Amgen, Sanofi The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mian, Puts, McCurdy, Wildes, Fiala, Kang, Salib, Alibhai and Mian.)

Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes., (© 2022. The Author(s).)

Optimizing end-of-life (EOL) care for multiple myeloma (MM) represents an unmet need. An administrative cohort in Ontario, Canada was analysed between 2006 and 2018. Aggressive care was defined as two or more emergency-department visits in the last 30 days before death, or at least two new hospitalizations within 30 days of death, or an intensive care unit (ICU) admission within the last 30 days of life. Supportive care was defined as a physician house-call in the last two weeks before death, or a palliative nursing or personal support visit at home in the last 30 days before death. Among 5095 patients, 23.2% of patients received chemotherapy at EOL and 55.6% of patients died as inpatient. A minority received aggressive care at EOL [28.3%: autologous stem cell transplant (ASCT), 20.4%: non-ASCT], and a majority received supportive care at EOL (65.4%: ASCT, 61.5%: non-ASCT). Supportive care was less likely to be received by those aged over 80 years and in lower-income neighbourhoods. Supportive care at EOL increased from 56.0% in 2006 to 70.3% in 2018. Despite improvements, many patients with MM experience aggressive care at EOL. Even in a publicly funded health care system, disparities based on age, income and community size are present., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: As the Canadian population ages, older adults comprise an increasing proportion of those diagnosed and treated for hematologic malignancies. A geriatric oncology curriculum has been recognized as a top priority in the care of older patients with cancer. It is not clear, however, whether hematology trainees receive training in geriatric oncology. We sought to understand residents' views and needs for a geriatric oncology curriculum during hematology residency in Canada., Materials and Methods: We conducted a cross-sectional needs assessment of hematology trainees enrolled in a Canadian residency or advanced fellowship training program within hematology. The survey, which was piloted with three non-hematology residents to ensure user-friendliness, used a combination of Likert scale, multiple-choice, and open-ended questions. The survey comprised three sections: (1) demographic data, (2) current state of geriatric oncology training (amount, content) and (3) attitudes towards learning about geriatric oncology and preferred curriculum components and identified needs. The survey was administered by the study team and distributed electronically to program directors in June 2020. The program directors were asked to forward the survey to trainees registered within their Division of Hematology. Data were analyzed descriptively., Results: Twenty-nine hematology residents participated (41.4% estimated response rate). Most respondents had not received geriatric oncology teaching (58.6%, n = 17) and have never been taught about geriatric oncology assessment tools (72.4%, n = 21) during hematology residency. Most respondents felt that their program should deliver a geriatric oncology curriculum (96.6%, n = 28). Respondents were most interested in learning about use of geriatric assessment tools for pre-treatment chemotherapy decision-making (86.2%, n = 25), prediction of chemotherapy toxicity (82.8%, n = 24), and to facilitate conversations regarding treatment initiation, continuation, or termination (79.3%, n = 23)., Discussion: Our study highlights the paucity of geriatric oncology training in hematology residency training programs. Our results highlight both the need and interest for a future dedicated geriatric oncology curriculum integrated into hematology training and provide guidance about which topics are most valued by trainees., Competing Interests: Declaration of Competing Interest Dr. Mithoowani has received honoraria from Leo Pharma. Dr. Hsu has received honoraria from Ipsen, Pfizer, Mylan and Eisai. Dr. Mian has received honoraria/advisory board fees from BMS, GSK, Pfizer, Janssen, FORUS, Amgen, Takeda, Sanofi and has research funding from Janssen., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Carfilzomib is an active and commonly used treatment in patients with multiple myeloma (MM). Using the Canadian Myeloma Research Group Database, we performed a retrospective observational study of patients treated with carfilzomib for relapse of MM in a real-world setting in Canada between years 2007 and 2020. A total of 445 patients were included in this study: the doublet (Kd/p, n  = 218) and triplets (KCd, n  = 88; KRd, n  = 99; KPd/p, n  = 40). One hundred and twenty-two (27%) received carfilzomib-based treatment in line 2, 133 (30%) in line 3, 90 (20%) in line 4, and 100 (23%) in line 5 or higher. Carfilzomib was dosed weekly in 40% of patients and twice weekly in 60%. The overall response rate of the entire cohort was 57.7%, with 33.6% of patients achieving very good partial response or better. Median progression-free survival for the overall cohort was 6.3 months with overall survival 19.7 months. This study provides a benchmark for carfilzomib-based regimens in the real world, demonstrating that these regimens are effective in treating patients with relapsed MM., Competing Interests: Arleigh McCurdy: honoraria—BMS, Janssen, Amgen, Takeda, Sanofi, and GSK. Martha Louzada: honoraria—Janssen, BMS, Amgen, and Pfizer. Christopher P. Venner: honoraria—Janssen, Amgen, and Takeda; research funding—BMS and Amgen. Victor H. Jimenez‐Zepeda: honoraria—Janssen, Takeda, Merck, and BMS. Richard LeBlanc: membership on an entity's Board of Directors or advisory committees—BMS Canada, Janssen Inc., Amgen Canada, Takeda Canada, and Sanofi Canada. Michael Sebag: membership on an entity's Board of Directors or advisory committees—Janssen Inc., Amgen Canada, Takeda Canada, and BMS Canada. Kevin Song: research funding—BMS; honoraria—BMS, Janssen, Amgen, and Takeda. Darrell White: honoraria—Amgen, Antengene, BMS, Janssen, Karyopharm, Sanofi, and Takeda. Hira Mian: honoraria—BMS, Janssen, Amgen, Takeda, Sanofi, and GSK; awards—HHS Research Early Career Award from Hamilton Health Sciences Foundation; research funding—Janssen. Rami Kotb: research funding—Merck and Sanofi; ownership/share holder—Karyopharm; honoraria—BMS, Janssen, Takeda, Amgen, Sanofi, and Merck. Donna Reece: research funding—Otsuka, BMS, Janssen, Takeda, Merck, BMS, and Millennium; consultancy—BMS, Janssen, Amgen, Karyopharm, and Takeda; honoraria—BMS, Janssen, Amgen, Takeda, Sanofi, and GSK. All remaining authors have declared no financial or perceived conflicts of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Considerable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization., Methods: The Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018., Results: A total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment., Conclusion: We present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: The globalization of clinical trials has accelerated recent advances in multiple myeloma (MM). However, it is unclear whether trial enrollment locations are reflective of the global burden of MM and whether access to novel therapies is timely and equitable for countries that participate in those trials., Methods: To assess this, we characterized where MM trials that led to US Food and Drug Administration (FDA) approvals were conducted and determined how often and quickly these drug regimens received approval in their participating trial countries on the basis of country income level and geographic region., Results: A systematic review was conducted to identify all MM clinical trials that met their primary endpoint, enrolled patients outside the United States, and resulted in FDA approval from 2005 to 2019. A total of 18 pivotal MM clinical trials were identified. High-income countries enrolled patients in 100% (18/18) of the trials identified, whereas upper-middle and lower-middle-income countries were represented in 61% (11/18) and 28% (5/18) of trials, respectively. No patients from low-income countries were enrolled. One trial enrolled patients in sub-Saharan Africa, and no trials enrolled patients in South Asia/Caribbean. For drugs/regimens that were approved in their participating countries, the median time from FDA approval to approval was 10.9 months. There were no drugs approved in lower-middle-income trial countries. MM trials leading to FDA approval are generally run in high-income, European, and Central Asian countries., Conclusion: There are substantial disparities in where novel therapies are evaluated and where they are ultimately approved for use on the basis of income level and geography., Competing Interests: Douglas W. SborovConsulting or Advisory Role: Sanofi, GlaxoSmithKline, Bristol Myers Squibb/Celgene, Legend Biotech, Janssen, Skyline Diagnostics Dickran KazandjianHonoraria: Arcellx, BMS, SanofiSpeakers' Bureau: Curio Science, Aptitude Health, Cure Educated Patient, Plexus Hira MianHonoraria: Celgene, Janssen, Takeda, Pfizer, Amgen, GlaxoSmithKlineConsulting or Advisory Role: Amgen, TakedaResearch Funding: Janssen Oncology Ola LandgrenHonoraria: Celgene, Bristol Myers Squibb, Medscape, Amgen, Janssen, Karyopharm TherapeuticsConsulting or Advisory Role: Bristol Myers Squibb, Celgene, Janssen, GlaxoSmithKlineResearch Funding: Amgen (Inst), Janssen (Inst), Pfizer (Inst) James HoffmanStock and Other Ownership Interests: SyndaxHonoraria: Bristol Myers Squibb/CelgeneNo potential conflicts of interest were reported.

Daratumumab (dara) has significantly altered the therapeutic landscape of multiple myeloma (MM), especially in the relapsed setting. This study aimed to evaluate the outcomes of dara-containing regimens in the Canadian real-world setting among relapsed and refractory MM available within the national Canadian Myeloma Research Group Database (CMRG-DB). A total of 583 MM patients who received dara-based therapy in second-line or later treatment were included. After a median follow-up of 17.5 months, the median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 13.1 and 32.9 months, respectively. The median PFS and OS were 23.5 and 49.1 months in second-line treatment and decreased to 12.8 and 43.0 months in third-line and 7.0 and 20.5 months in fourth-line treatment respectively. Dara in monotherapy with or without corticosteroids after a median of four prior lines of therapy resulted in a median PFS of 3.9 months and a median OS of 17.1 months. The addition of bortezomib, lenalidomide or pomalidomide to dara resulted in an improved median PFS and OS of 8.3 and 26.2 months; 26.8 and 43.0 months; and 9.7 and 31.4 months respectively. These retrospective data from the CMRG-DB suggest that outcomes are superior when dara is used in combination and in earlier lines of treatment., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Gender disparities exist in academia and are disproportionately affecting females. We conducted a cross-sectional study to analyze gender disparities in multiple myeloma (MM) publications. A total of 679 publications with 8898 authorships were analyzed. The mean number of authors for females vs. males, per publication, was 4.4 and 8.7, respectively. Females constituted a third of the total authors. Female first authors, corresponding authors, and last/senior authors were 34%, 21%, and 18%, respectively. Note that, 17% of authors of clinical trial publications were females. Gender disparities in MM publications exist and are more obvious in the last/corresponding authorship. Efforts should be made to identify factors that contribute to these disparities and work to resolve them., Competing Interests: Aala Dweik, Hadeel Dweik, Meera Mohan, and Samer Al Hadidi report no relevant conflict of interest. Hira Mian receives advisory fees from Janssen, GSK, Celgene/BMS, Takeda, Sanofi, and research funding from Janssen. Hira Mian is the recipient of an early career research award from Hamilton Health Sciences., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Hematologic malignancy outcomes have remarkably improved in the past decade with further advancement expected in future years. However, the detrimental effects of financial toxicity (FT) on patients with hematologic malignancies, because of both diagnoses and subsequent treatments, have not been studied comprehensively. We performed a systematic review of all studies reporting FT as a primary or secondary outcome among adult or pediatric patients with hematological malignancies. A total of 55 studies met the inclusion criteria for analysis. Across studies, 20-50% of patients reported some form of FT, including loss of work productivity, food and transportation costs, and depletion of savings. Younger age, lower-income level, unemployment, and rural residence were the most commonly identified risk factors for FT. Two studies looked at survival outcomes, with one reporting improvement in survival with a decrease in financial toxicity. However, significant heterogeneity in FT definitions was found between countries and payor systems. Only half of the studies (51%, n = 28) used validated survey instruments such as the COST assessment. The present systematic review identified that FT is common in patients with hematological malignancies and may be associated with poorer outcomes. However, studies of FT generally use non-standardized methods with cross-sectional analyses rather than longitudinal, prospective assessments. Further work is needed to standardize FT reporting and investigate measures to alleviate FT among patients with hematologic malignancies., (© 2022. The Author(s).)

The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database. A total of 121 patients were reviewed, 49 patients received CAR- before POM-based (CAR-POM), and 73 patients received POM- before CAR-based (POM-CAR) therapy. In the groups selected, the median PFS was 4.93 months (95% CI, 2.76-7.07) and 5.36 months (95% CI, 3.75-6.94) for CAR-POM and POM-CAR, respectively. The median OS for patients treated with CAR-POM was 11.01 months (95% CI, 4.50-19.13), and for patients treated with POM-CAR the median OS was 10.98 months (95% CI, 8.98-19.17). In this real-world observational study, we demonstrated that both CAR- and POM-based therapies, irrespective of the order in which they were used, were effective treatment options for patients with advanced relapsed MM.

Background: Daratumumab, a monoclonal antibody directed against CD38 is a recent class of drugs introduced into the multiple myeloma therapeutic landscape. While clinical trial data have shown a remarkable impact on outcomes, the efficacy of daratumumab combination therapies in specific clinically relevant subgroups including among patients refractory to lenalidomide maintenance remains unknown., Methods: In this study, retrospective data were reviewed from the Canadian Myeloma Research Group and the German Munster Myeloma databases to identify patients that received daratumumab in combination with pomalidomide (DPd), lenalidomide (DRd), and bortezomib (DVd) in a population that had relapsed on lenalidomide maintenance postautologous stem cell transplant. The primary aim of the study was to look at outcomes of these patients in different daratumumab combinations., Results: A total of 73 patients were identified. The median age of the patients at the time of daratumumab initiation was 60 (38-72) and 64.4% ( n = 47) were men. In the selected cohort, 43.8% ( n = 32) were treated with DRd, 31.5% ( n = 23) with DVd, and 24.7% ( n = 18) with DPd regimen. The median progression-free survival (PFS) of the entire cohort was 15.8 months (95% CI, 12.9-37.1 months). The median PFS of the individual regimens was as follows: DPd 18.9 months (95% CI, 13.7-not reached), DRd 21.7 months (95% CI, 11.6-not reached), and DVd 12.9 months (95% CI, 3.1-not reached)., Conclusions: Daratumumab-containing therapies are effective regimens in patients progressing on lenalidomide maintenance. Additional studies are required to decide the optimal regimen post-lenalidomide maintenance., Competing Interests: HM: Honoraria: Celgene, Janssen, Amgen, Takeda, Sanofi, and GSK. Awards: Research Early Career Award from Hamilton Health Sciences Foundation. Research funding: Janssen. CV: Honoraria: Janssen, Amgen, and Takeda. Research funding: Celgene and Amgen. VJ-Z: Honoraria: BMS, Amgen, Takeda, and Janssen. AM: Honoraria: Celgene, Janssen, Amgen, Takeda, Sanofi, and GSK. MS: membership on an entity’s Board of Directors or advisory committees: Janssen Inc., Amgen Canada, Takeda Canada, and Celgene Canada. KS: Research funding: Celgene. Honoraria: Celgene, Janssen, Amgen, and Takeda. RL: Membership on an entity’s Board of Directors or advisory committees: Celgene; Canada; Janssen Inc.; Amgen Canada; Takeda Canada; Research Funding: Celgene; White: Honoraria and consultancy: Amgen, Celgene, Janssen, Sanofi, Takeda; Louzada: Honoraria: Janssen, Celgene, Amgen, Pfizer; Kotb: Research funding: Merck, Sanofi. Ownership/Share holder: Karyopharm. Honoraria: Celgene/BMS, Janssen, Takeda, Amgen, Sanofi, Merck; Reece: Research funding: Otsuka, Celgene, Janssen, Takeda, Merck, BMS, and Millennium. Consultancy: Celgene, Jansen, Amgen, Karyopharm, and Takeda. Honoraria: Celgene, Janssen, Amgen, Takeda, and GSK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mian, Eisfeld, Venner, Masih-Khan, Kardjadj, Jimenez-Zepeda, Khandanpour, Lenz, McCurdy, Sebag, Song, LeBlanc, White, Stakiw, Reiman, Louzada, Aslam, Kotb, Gul and Reece.)

The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, (p < 0.01), REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)% (p < 0.01), PFS 27.8 (22.4-33.5)% vs. 9.8 (5.5-15.2)% (p < 0.01), and OS 54 (47.5-60.5)% vs 30.9 (23.2-39.2)% (p < 0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p = 0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Autologous stem cell transplant (ASCT) is an established treatment for patients with newly diagnosed multiple myeloma (NDMM). Understanding the symptom burden associated with ASCT may be an important consideration for patients with NDMM when selecting treatment options., Patients and Methods: We conducted a population-based study of patients who underwent an ASCT for NDMM in Ontario, Canada, between 2007 and 2018. The patient-reported outcome, Edmonton Symptom Assessment System (ESAS) score, which captures nine common cancer-associated symptoms and is routinely collected at all outpatient visits, was linked to provincial administrative healthcare data. The monthly prevalence of moderate or severe symptoms (ESAS ≥ 4) each month in the first year following ASCT was analyzed. A multivariable logistic regression model was used to identify factors associated with moderate to severe symptoms., Results: In our final cohort of 1969 patients who had undergone an ASCT, a total of 12,820 unique assessments were captured. Symptom burden was highest at 1 month post-ASCT, with moderate to severe tiredness and impaired well-being being the two most common symptoms. Symptom burden substantially improved by 3 months post-ASCT, reaching a new baseline for the year following. On multivariable analysis, female sex, increased co-morbidities, earlier year of diagnosis, and myeloma-related end-organ damage (specifically, bone and kidney disease) were associated with a higher odds of reporting moderate to severe symptoms., Conclusion: In this large population-based study using patient-reported outcomes, there was a substantial burden of symptoms noted among NDMM patients 1 month post-ASCT, which improved over time. Tailored supportive care interventions should focus on strategies to optimize management of identified symptoms., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Multiple myeloma (MM) is a cancer of older adults with a median age at diagnosis of 70 years. Our study aimed to understand the changes that occurred in geriatric domains and quality of life parameters as older adults underwent treatment for MM over 6-months following initial diagnosis., Methods: This was a secondary analysis of a prospective cohort study of 40 adults aged ≥65 with newly-diagnosed MM who completed the Cancer and Aging Research Group geriatric assessment and the Functional Assessment of Cancer Therapy (General and subscale Gynecologic Oncology Group-Neurotoxicity) quality of life tool at baseline and at 6 months following treatment initiation., Results: Thirty-six participants completed 6-months of follow-up. There was no significant change in geriatric domains, including dependence in instrumental activities of daily living (IADLs). Compared to baseline, mental health improved at 6-months of follow-up (Mental Health Inventory-17 score, median 77.1 versus 84.3 at baseline and 6-months respectively, p < .001). Objective physical performance as measured by the Timed Up and Go test showed a trend towards improvement (12.3 versus 11.0 s, p = .057) and remained stable or improved in almost all (30/32, 93.8%) of the adults using the minimum clinically important difference threshold., Conclusion: From baseline to 6-months of follow-up, older adults with MM showed improvement in mental health but otherwise remained stable with regards to function and overall quality of life. Timed Up and Go Test may provide a dynamic indicator of functional status and needs to be further evaluated in future studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This approach to the work-up and diagnosis will help you to ensure prompt treatment while maximizing your patient's quality of life.

Competing Interests: Declaration of Competing Interest None.

Until recently, the progress in the diagnosis and management of cancer has not been matched by similar progress in the assessment of the increasing numbers of older and more complex patients with cancer. Dr. Arti Hurria identified this gap at the outset of her career, which she dedicated toward studying the geriatric assessment (GA) as an improvement over traditional methods used in oncology to assess vulnerability in older patients with cancer. This review documents the progress of the GA and its integration into oncology. First, we detail the GA's origins in the field of geriatrics. Next, we chronicle the early rise of geriatric oncology, highlighting the calls of early thought-leaders to meet the demands of the rapidly aging cancer population. We describe Dr. Hurria's early efforts toward meeting these calls though the implementation of the GA in oncology research. We then summarize some of the seminal studies constituting the evidence base supporting GA's implementation. Finally, we lay out the evolution of cancer-focused guidelines recommending the GA, concluding with future needs to advance the next steps toward more widespread implementation in routine cancer care. Throughout, we describe Dr. Hurria's vision and its execution in driving progress of the GA in oncology, from her fellowship training to her co-authored guidelines recommending GA for all older adults with cancer-published in the year of her untimely death., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: One of the most common orally administered antimyeloma agents, lenalidomide, has significantly improved outcomes in multiple myeloma, including in older patients. However, despite its utilization and cost, the rates and factors related to adherence to lenalidomide in older adults with newly diagnosed multiple myeloma remain unknown., Patients and Methods: Data were collected from adults with newly diagnosed multiple myeloma over age 65 years being treated with lenalidomide therapy between the years 2007 and 2014 in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Adherence was measured as medication possession ratio (MPR), which was defined as the ratio of the number of days the patient had pills in their possession to the number of days in the observation period in the first year after myeloma diagnosis. MPR of < 90% was considered poor adherence., Results: A total of 793 patients were included in the analysis. The mean MPR in our cohort was 89.5 ± 9.3%. Overall, 38% (n = 302) of the patients were considered to have poor adherence. Factors associated with poor adherence included increasing age (adjusted odds ratio [aOR] = 1.03 per year; 95% confidence interval [CI], 1.00-1.05; P = .024), black race (aOR = 1.72; 95% CI, 1.08-2.73; P = .022), and polypharmacy (aOR = 1.04 per medication; 95% CI, 1.01-1.08; P = .008)., Conclusion: Over a third of older adults with newly diagnosed multiple myeloma were considered to have poor adherence to lenalidomide, using the MPR as a surrogate for adherence. This highlights the need to further understand factors and devise strategies to support adherence in this patient cohort., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: While autologous stem cell transplant (ASCT) is a standard of care for newly-diagnosed younger patients with multiple myeloma, its role in older patients remains controversial. We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) assessing the efficacy and toxicity of ASCT in older patients (age ≥ 65 years) with newly-diagnosed myeloma., Methods: We searched Medline, Embase, and the Cochrane database through February 2, 2018. The primary outcome was overall survival; secondary outcomes included progression-free survival, response rates and toxicity. The Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE) method was used to assess certainty in evidence., Results: Of 8614 abstracts screened, six observational studies and two RCTs were included in the systematic review. For overall survival, pooled observational data favored ASCT (Hazard Ratio [HR] 0.44, 95% Confidence Interval [CI] 0.34-0.58, p < .0001), while the impact of the RCT data was uncertain (HR 0.94, 95% CI 0.25-3.54, p = .93). Observational data showed higher complete response rates with ASCT (odds ratio 5.06, 95% CI 2.60-9.88, p < .0001). Progression free survival benefit from the RCTs was uncertain (HR 1.05, 95% CI 0.36-3.12, p = .93). Data were insufficient to pool for toxicity., Conclusion: For older patients with newly diagnosed multiple myeloma, ASCT may improve the overall survival and complete response rates based upon observational data although the quality of this evidence is very low. The role of ASCT in improving overall survival based upon RCT data remains uncertain with low quality of evidence. Our study highlights the urgent need for well-conducted studies to understand the role of ASCT in older patients., (Copyright © 2019. Published by Elsevier Ltd.)

The DNA binding of amphiphilic iron(III) 2,17-bis(sulfonato)-5,10,15-tris(pentafluorophenyl)corrole complex (Fe-SC) was studied using spectroscopic methods and viscosity measurements. Its nuclease-like activity was examined by using pBR322 DNA as a target. The interaction of Fe-SC with human serum albumin (HSA) in vitro was also examined using multispectroscopic techniques. Experimental results revealed that Fe-SC binds to ct-DNA via an outside binding mode with a binding constant of 1.25 × 10(4) M(-1). This iron corrole also displays good activity during oxidative DNA cleavage by hydrogen peroxide or tert-butyl hydroperoxide oxidants, and high-valent (oxo)iron(V,VI) corrole intermediates may play an important role in DNA cleavage. Fe-SC exhibits much stronger binding affinity to site II than site I of HSA, indicating a selective binding tendency to HSA site II. The HSA conformational change induced by Fe-SC was confirmed by UV/Vis and CD spectroscopy., (Copyright © 2015 John Wiley & Sons, Ltd.)

The antimicrobial activity of Grossman's sealer and its components was evaluated on 13 different strains using the double layer well-diffusion method. Results revealed that Grossman's sealer presented antimicrobial activity against all the tested strains. Among the components of the cement, sodium tetraborate presented the greatest antimicrobial activity, both in type and diameter of the halo and ring of inhibition. Sealer powder, rosin, and eugenol presented similar activity, with no effect on P. aeruginosa and C. albicans. Among these, only eugenol had an effect on E. coli. Zinc oxide was only active against S. sobrinus and E. coli. Barium sulfate and bismuth subcarbonate did not show any antimicrobial effect.