A real-world data analysis of predictors of early mortality after a diagnosis of multiple myeloma.

BACKGROUND: Despite the increased availability and use of novel therapies for multiple myeloma, early mortality is a pervasive challenge with a significant impact on older adults. Reported rates and predictors of early mortality have varied in the literature, with most studies seldom focusing on community-treated patients. METHODS: In this retrospective cohort analysis of a real-world electronic health record-derived deidentified database of 7512 patients newly diagnosed with multiple myeloma between January 1, 2011, and February 2, 2021, and treated primarily in US-based community oncology practices, factors associated with early mortality (defined as death within 6 months after the multiple myeloma diagnosis) were examined with the use of binary logistic regression. RESULTS: The median age was 70 years overall. We found an overall early mortality rate of 8.3%, with 73% of early deaths occurring in those aged ≥70 years. Among the early deaths, only 49 patients (8.7%) had documented disease progression before death (median time to progression, 30 days [interquartile range, 7-53 days]). Baseline factors associated with higher odds of early mortality included an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, Revised International Staging System (R-ISS) stage III, an age ≥ 70 years, receipt of proteasome inhibitor-doublet therapy, a light-chain isotype, and the presence of renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Among those aged ≥70 years, ECOG PS ≥ 2 and R-ISS stage III remained the strongest predictors of early mortality. CONCLUSIONS: Early mortality disproportionately affects older adults (aged ≥70 years) with multiple myeloma. Interventions to support this population are needed to reduce disparate survival outcomes. PLAIN LANGUAGE SUMMARY: Factors associated with an increased risk of dying within 6 months (early mortality) of a new diagnosis of multiple myeloma (MM) among 7512 mostly community-treated patients with MM were evaluated. The early mortality rate was 8.3%; among those deaths, 49 patients (8.7%) had documented evidence of MM progression before death. The risk of early mortality was greatest for older patients (aged ≥70 years) and those with a poor performance status, poor kidney function, a higher disease stage, and light-chain MM and those receiving two-drug MM therapies. These findings highlight the need for supportive interventions geared toward older adults with MM.

Physical Function, Psychosocial Status, and Symptom Burden Among Adults with Plasma Cell Disorders and Associations with Quality of Life.

BACKGROUND: The plasma cell disorders (PCDs), multiple myeloma (MM), and light-chain amyloidosis (AL) are disproportionately diseases of older adults, whose care may be complicated by frailty associated with advancing age. We sought to evaluate the prevalence of functional deficits and symptoms in a cohort of persons with PCDs and associations of demographic, disease-related, functional, and psychosocial measures with quality of life (QoL). PATIENTS AND METHODS: Adults with PCDs were recruited into an observational registry in 2018-2020. Patients completed a functional assessment and European Organization for Research and Treatment of Cancer QoL questionnaire (QLQ-C30). Associations of covariates of interest with QoL were evaluated via univariate linear regression. RESULTS: Among 121 adults, the mean age was 68.6. Diagnoses were 74% MM, 14% AL, 7% both MM and AL, and 5% other PCDs. The median time from diagnosis was 34.9 months. Median lines of therapy were 2, with 11% having received ≥4th-line therapy.Patients with functional deficits had lower mean QoL scores: dependence in IADLs (66.3 vs. 79.9, P = .001) and recent falls (56.7 vs. 76.8, P = .001). Patients ≤6 months from diagnosis had lower QoL (66.7) than those ≥2 years from diagnosis (77.3, P = .03). However, patients on later lines of therapy (≥4th-line) had lower QoL (62.2) than those on 1st-line treatment (76.0, P = .04). CONCLUSIONS: Patients with physical impairments and more advanced PCDs had lower QoL than those without deficits or earlier in their disease course. Early identification of physical impairments may facilitate interventions that mitigate these deficits and thereby improve QoL for patients with PCDs.

Quality of direct oral anticoagulant prescribing in elderly patients with non-valvular atrial fibrillation: results from a large urban health system.

Non-valvular atrial fibrillation (NVAF) is common in older adults. Oral anticoagulation is indicated to reduce the risk of stroke and systemic embolism, but it also poses a risk of bleeding, particularly in the elderly. Direct oral anticoagulants (DOACs) provide an alternative to warfarin and their use in the treatment of AF is growing. We conducted a retrospective cohort study to assess the quality of DOAC prescribing in elderly patients with NVAF in a large academic health system and to compare practice with consensus best practice recommendations. We searched the electronic medical record for patients ≥ 65 years of age who were newly initiated on a DOAC for AF from January 2013 through December 2015. Patient and provider characteristics, baseline laboratory investigations, concomitant medications, and interval to first follow-up were recorded. 192 patients met eligibility criteria. The most commonly prescribed DOACs were rivaroxaban (65%) and apixaban (26%). Despite consensus recommendations that patients have a baseline creatinine, complete blood cell count, and coagulation studies prior to DOAC initiation, these tests were not performed in 18, 31, and 67% of patients, respectively. Consensus recommendations also suggest a follow-up visit within 1 month of DOAC initiation. However, only 39% of patients had a return visit within 6 weeks and 43% did not have follow-up within 12 weeks. DOAC prescribing in elderly patients with NVAF frequently fell short of quality standards. Interventions to enhance the quality of DOAC prescribing in this high-risk population are needed.

"First, Trust Needs to Develop": Hematologists' Perspectives on Factors Influencing Black Persons' Participation in Clinical Trials.

BACKGROUND: Cancer clinical trials are crucial for treatment standards and innovation but lack racial-ethnic diversity. Understanding physician perspectives on recruiting participants is critical due to their role in decision-making about trial candidacy and enrollment. METHODS: From August 2021 to January 2022 we recruited 13 Academic hematologists experienced with treating blood cancers and enrolling clinical trial participants. Each hematologist participated in a 60-75-minute semistructured interview and completed a sociodemographic survey. Using the National Institute on Minority Health and Health Disparities multilevel model as a framework, we characterized hematologists' perceived barriers to clinical trial participation among Black persons. ATLAS.ti v9 and later v 23.2.1 was used for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk Inc). RESULTS: All hematologists were White, with 70% being male. Three factors influenced their perspectives on enrolling Black individuals in clinical trials: individual attitudes and beliefs, such as perceptions that Black or socioeconomically disadvantaged persons will be less willing or less compliant with the requirements for trial participation and follow-up. The need to build trusting relationships between themselves and patients prior to discussing clinical trials and the prevailing legacy of medical mistrust among the Black community. Trust was found to be the underlying factor in determining communication between hematologists and Black persons about clinical trials across all three levels. CONCLUSION: This study highlights how hematologists' attitudes, beliefs, biases, and views on trust in patient relationships influence their communication with Black individuals about clinical trials. It emphasizes the need for further research to develop interventions that address the lack of racial and ethnic diversity in trials.

Systematic Review of Interventions Addressing Racial and Ethnic Disparities in Cancer Care and Health Outcomes.

PURPOSE: Cancer health disparities result from complex interactions among socioeconomic, behavioral, and biological factors, disproportionately affecting marginalized racial and ethnic groups. The objective of this review is to synthesize existing evidence on interventions addressing racial or ethnic disparities in cancer-related health care access and clinical outcomes. METHODS: A comprehensive search of Cochrane Library, Google Scholar, Ovid MEDLINE, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection was conducted from database inception to February 23, 2023. Controlled vocabulary and keywords helped to identify studies on cancer-related disparities and interventions in adults age 18 years or older. Two reviewers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tool. RESULTS: Of 7,526 screened studies, 34 met the inclusion criteria involving 24,134 participants. Most studies focused on breast cancer (n = 17) and Hispanic/Latino populations (n = 10) and enrolled participants primarily from community-based sites (n = 19). Twenty-one studies examined patient-centered outcomes, such as health-related quality of life and psychological well-being, while 15 studies assessed process-of-care outcomes, such as timeliness of care. Most studies followed a community-based participatory research framework. Five patient-centered outcome studies reported a positive intervention effect, often combining cancer education with psychological well-being interventions. Among the 15 process-of-care outcome studies, nine reported positive effects, with the majority (n = 8) being navigation-based interventions. CONCLUSION: This systematic review emphasizes the vital role of community partnerships in addressing racial and ethnic disparities in oncology care and highlights the need for standardized approaches in intervention research because of the heterogeneity of studied interventions. Furthermore, the prevailing emphasis on breast cancer and Hispanic populations indicates the need for future investigations into other priority demographic groups.

A scoping review of racial, ethnic, socioeconomic, and geographic disparities in the outcomes of older adults with cancer.

INTRODUCTION: Cancer health disparities are widespread. Nevertheless, the disparities in outcomes among diverse survivors of cancer ages 65 years and older ("older") have not been systematically evaluated. METHODS: We conducted a scoping review of original research articles published between January 2016 and September 2023 and indexed in Medline (Ovid), Embase, Scopus, and CINAHL databases. We included studies evaluating racial, ethnic, socioeconomic disadvantaged, geographic, sexual and gender, and/or persons with disabilities disparities in treatment, survivorship, and mortality among older survivors of cancer. We excluded studies with no a priori aims related to a health disparity, review articles, conference proceedings, meeting abstracts, studies with unclear methodologies, and articles in which the disparity group was examined only as an analytic covariate. Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. RESULTS: After searching and removing duplicates, 2573 unique citations remained and after screening 59 articles met the inclusion criteria. Many investigated more than one health disparity, and most focused on racial and ethnic (n = 44) or socioeconomic (n = 25) disparities; only 10 studies described geographic disparities, and none evaluated disparities in persons with disabilities or due to sexual and gender identity. Research investigating disparities in outcomes among diverse older survivors of cancer is increasing gradually-68% of eligible articles were published between 2020 and 2023. Most studies focused on the treatment phase of care (n = 28) and mortality (n = 26), with 16 examined disparities in survivorship, symptoms, or quality of life. Most research was descriptive and lacked analyses of potential underlying mechanisms contributing to the reported disparities. CONCLUSION: Little research has evaluated the effect of strategies to reduce health disparities among older patients with cancer. This lack of evidence perpetuates cancer inequities and leaves the cancer care system ill equipped to address the unique needs of the rapidly growing and increasingly diverse older adult cancer population.

"They don't care to study it": Trust, race, and health care experiences among patient-caregiver dyads with multiple myeloma.

BACKGROUND: Medical mistrust, rooted in unethical research, is a barrier to cancer-related health care for Black/African American (AA) persons. Understanding trust, mistrust, and health care experiences is crucial, especially in multiple myeloma (MM), which disproportionately burdens Black/AA persons in incidence and survival. STUDY PURPOSE: This study qualitatively examines the experiences of Black/AA and White dyads (patient with MM and adult caregiver) to gain insights into these phenomena. METHODS: From November 2021 to April 2022, we recruited 21 dyads from the UNC Lineberger Comprehensive Cancer Center. Participants completed a sociodemographic survey and a 60-90 min semi-structured interview. We used ATLAS.ti v9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk Inc). RESULTS: We interviewed 21 racially concordant dyads (11 Black/AA, 10 White) with mean patient ages of 70 (Black/AA) and 72 (White) at enrollment. Both Black/AA and White caregivers had a mean enrollment age of 68. The mean duration from MM diagnosis to enrollment for all patients was 5.5 years. Four key themes emerged: (1) knowledge and trust, (2) heightened emotions and discomfort, (3) differing mental constructs of health care experiences, and (4) mitigating mistrust, which varied by self-identified race. Black/AA participants had greater knowledge of historical events like the U.S. Public Health Service Untreated Syphilis Study at Tuskegee and carried the emotional burden longer. They also emphasized self-learning and self-guided research about MM for informed medical decision-making. Both Black/AA and White dyads emphasized the pivotal role of patient-provider relationships and effective communication in fostering trust and addressing concerns. CONCLUSION: Our study offers contextual insights into the enduring challenges of medical mistrust, particularly within the Black/AA community, and its implications for patients and caregivers accessing and receiving MM-related care. Future studies should leverage these insights to guide the development of multilevel interventions addressing medical mistrust within the Black/AA community.

Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapy in Multiple Myeloma: Moving Into the Future.

Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective treatment options. However, the advent of chimeric antigen receptor (CAR) T-cell and T-cell redirecting bispecific antibody (BsAb) therapies has led to unprecedented response rates and durations of response in heavily relapsed/refractory (R/R) populations. Currently, two B-cell maturation antigen (BCMA)-directed CAR T-cell therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) as well as one BCMA/CD3 BsAb (teclistamab) have been approved for late-line (greater than four previous lines) R/R MM in the United States. The purpose of this review is to analyze the recent data for these approved therapies as well as provide an overview of other related CAR T-cell and BsAb therapies under development, including non-BCMA-targeting agents. We review efficacy and safety considerations, with particular focus on cytokine release syndrome, neurotoxicity, and infection risk. The relative merits and limitations of each class of therapy are discussed, as well as the areas of unmet need with respect to optimal sequencing and supportive care measures. We examine the factors that challenge equitable access to these novel therapies across minoritized racial, ethnic, and socioeconomic populations. Although it is evident that CAR T-cell and BsAb therapies will transform treatment paradigms in MM for years to come, significant work remains to identify the optimal utilization of these novel therapies and ensure equitable access.

Partnering With All Patients: Ensuring Shared Decision Making and Evidence-Based Management for Underrepresented Groups With Multiple Myeloma.

Several landmark therapeutic advances in multiple myeloma (MM) have led to an unprecedented number of options available to patients and their physicians as shared decision making is attempted. A myriad of factors need to be considered to ensure that patient-, disease-, and treatment-related factors are addressed to arrive at the most appropriate choice for patients at that time in their journey with myeloma. Some of these factors have traditionally remained underaddressed but have a clear association with patient outcomes, leading to underrepresented groups of patients with MM, including the elderly patients, racial-ethnic minorities, and those with specific advanced comorbidities, for example, renal insufficiency. Some of these factors may not be modifiable, but data suggest that they may give rise to implicit or explicit bias and affect treatment decisions. A growing body of literature is bringing these factors to light. However, their incorporation in day-to-day decision making for patients needs to be universal. It is imperative that prospective data are generated for all these and other underrepresented groups such that evidence-based medicine is applicable universally to all patients with MM, irrespective of clinical and sociodemographic factors.

Global disparities in patients with multiple myeloma: a rapid evidence assessment.

There are disparities in outcomes for patients with multiple myeloma (MM). We evaluated the influence of sociodemographic factors on global disparities in outcomes for patients with MM. This rapid evidence assessment (PROSPERO, CRD42021248461) followed PRISMA-P guidelines and used the PICOS framework. PubMed and Embase® were searched for articles in English from 2011 to 2021. The title, abstract, and full text of articles were screened according to inclusion/exclusion criteria. The sociodemographic factors assessed were age, sex, race/ethnicity, socioeconomic status, and geographic location. Outcomes were diagnosis, access to treatment, and patient outcomes. Of 84 articles included, 48 were US-based. Worldwide, increasing age and low socioeconomic status were associated with worse patient outcomes. In the US, men typically had worse outcomes than women, although women had poorer access to treatment, as did Black, Asian, and Hispanic patients. No consistent disparities due to sex were seen outside the US, and for most factors and outcomes, no consistent disparities could be identified globally. Too few studies examined disparities in diagnosis to draw firm conclusions. This first systematic analysis of health disparities in patients with MM identified specific populations affected, highlighting a need for additional research focused on assessing patterns, trends, and underlying drivers of disparities in MM.

"A lot to manage and still have some kind of a life": How multiple myeloma impacts the function and quality-of-life of Black-White patient-caregiver dyads.

BACKGROUND: Multiple myeloma (MM) is an incurable debilitating blood cancer associated with the lowest health related quality of life (HRQoL) of all cancers. With nearly 88% of adults aged ≥55 years at diagnosis, age-associated physical losses, comorbidities, and social factors contribute to worsening HRQoL. This qualitative study assessed dyadic (patient-informal caregiver) perspectives on the factors contributing to HRQoL in MM survivors. METHODS: We recruited 21 dyads from the UNC-Chapel Hill Lineberger Comprehensive Cancer between 11/2021 and 04/2022. Participants completed a single dyadic semistructured interview capturing broad perspectives on MM. We used ATLAS. ti v 9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk, Inc.). This iterative approach allowed the exploration and identification of themes within and across transcripts. RESULTS: The mean age at enrollment was 71 years (median: 71, range: 57-90) for patients and 68 years (median 67, range: 37-88) for caregivers. All dyads were racially concordant (11 Black/AA and 10 White). However, we aggregated the findings due to no consistent racial differences. Six themes related to (1) physical burden, (2) treatment challenges, (3) losses of independence, (4) caregiver burden, (5) patient and caregiver perseverance, and (6) adjustment to a new normal were identified. Dyads also experienced MM together, resulting in patients and caregivers experiencing changes in their ability to engage in physical and social activities, which further contributed to poor HRQoL. Patients' increased need for social support led to shifts in the caregiver roles, resulting in caregivers feeling burdened by their responsibilities. All dyads acknowledged the need for perseverance and adaptability to a new normal with MM. CONCLUSION: The functional, psychosocial, and HRQoL of older patients with MM and their caregivers remain impacted ≥6 months after a new diagnosis highlighting clinical and research opportunities to focus on preserving or improving the health of dyads living with MM.

Cross-Sectional Analysis of Clinical Trial Availability and North Carolina Neighborhood Social Vulnerability.

PURPOSE: Residents of communities facing social vulnerability (eg, poverty) have limited access to clinical trials, leaving them susceptible to experiencing poor health outcomes. We examined the association between North Carolina county-level social vulnerability and available multiple myeloma (MM) trials. METHODS: Using a novel data linkage between ClinicalTrials.gov, the 2019 American Community Survey, and the Centers for Disease Control and Prevention's Social Vulnerability Index, we investigated at the county level (1) availability of MM trial sites and (2) the relationship between Social Vulnerability Index and MM trial site availability using logistic regression. RESULTS: Between 2002 and 2021, 229 trials were registered across 462 nonunique trial sites in 34 counties. Nearly 50% of trial sites were in academic medical centers, 80% (n = 372) of all trials were industry-sponsored, 60% (n = 274) were early-phase, and 50% (n = 232) were for patients with relapsed or refractory MM. Counties with low as opposed to high poverty rates had six times greater odds of having ≥ 1 MM trial sites (odds ratio [OR], 5.60; 95% CI, 1.85 to 19.64; P = .004). Counties with the lowest percentage of Black Indigenous Persons of Color and non-native English speakers had 77% lower odds (OR, 0.23; 95% CI, 0.07 to 0.69; P = .011) of having ≥ 1 trial sites. The effect remained significant after accounting for the presence of five academic medical centers (n = 95; OR, 0.18; 95% CI, 0.05 to 0.6; P = .008) and adjustment for metropolitan, suburban, or rural status (OR, 0.25; 95% CI, 0.07 to 0.81; P = .025). CONCLUSION: Counties with the lowest poverty rates had more MM trial sites, whereas those with the lowest percentage of Black Indigenous Persons of Color populations had fewer MM trial sites. Multilevel efforts are needed to improve the availability and access to trials for socially vulnerable populations.

Opportunities, challenges, and future directions for simulation modeling the effects of structural racism on cancer mortality in the United States: a scoping review.

PURPOSE: Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States. RESULTS: A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents. CONCLUSIONS: A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.

SOHO State of the Art Updates and Next Questions: Treatment of Older, Vulnerable Adults with Multiple Myeloma.

Multiple myeloma is primarily a disease of the elderly, and optimal treatments must weigh the risks of toxicity with the benefits of therapy.  Frailty scales have been developed to aid treatment-decision making for older adults with MM.   This review provides a framework for incorporating frailty scales into clinical care and highlights how patient-aligned priorities for care can influence the management of older or more vulnerable adults with newly diagnosed multiple myeloma newly diagnosed multiple myeloma. We review the currently available systemic therapies for managing older or more vulnerable adults with newly diagnosed multiple myeloma otherwise considered ineligible for autologous stem cell transplantation.

Use of geriatric assessment in cancer clinical trials: A systematic review.

BACKGROUND: Older adults are underrepresented in cancer clinical trials despite accounting for most of the disease burden. Geriatric assessment (GA) could be used in clinical trials of cancer drugs for older adults to improve the clinical evidence for cancer drug use among older adults. OBJECTIVE: To examine patterns of use of GA in cancer clinical trials. METHODS: We undertook a systematic review of the studies reporting use of GA in a clinical trial setting for all cancer types and published between January 2010 and January 2020. Characteristics of GA use were extracted for each study, along with study phase, cancer type, and participant age (PROSPERO: CRD42020170584). RESULTS: We identified 320 studies and 63 studies met the final inclusion criteria. Among 74 purposes of GA use, the most common was to examine the association between impairments in GA domains and clinical outcomes (28/74, 38%). Among 258 GA domains assessed across 63 studies, physical status (59/258, 23%) and comorbidities (50/258, 19%) were most often evaluated. There was significant heterogeneity in the instruments used to assess physical function (n = 16) and mood disorders (n = 7). Most studies were phase 2 (32/63, 51%). CONCLUSIONS: GA is most often used in clinical trial settings to examine associations between GA-identified deficits and clinical outcomes. Significant heterogeneity exists in the GA instruments used across trials. Comprehensive and consistent incorporation of GA into future cancer clinical trial designs could help collect more older adult-specific clinical information and adjust trial eligibility criteria to increase representation by older adults.

Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.

Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS. A literature search of Ovid Medline, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar was conducted from each database's inception through February 1, 2022, using search terms reflecting CAR T cell therapy and ICANS. We included studies that enrolled adults (age ≥18 years) who received CAR T cell therapy as management for hematologic malignancies and reported the clinical presentation, predictors, and/or acute or long-term outcomes of ICANS. Two reviewers independently extracted data following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) reporting guidelines. Quality was assessed using the Joanna Briggs Institute critical appraisal tool for cohort studies. Of the 2928 studies screened, 23 observational studies (10 prospective, 11 retrospective, 1 mixed design, and 1 cross-sectional) with a total of 1666 participants met our eligibility criteria and were included in our review. The most common hematologic malignancies were diffuse large B cell lymphoma, acute lymphocytic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. ICANS onset was most often associated with the presence and severity of cytokine release syndrome, as well as with C-reactive protein and ferritin levels. Aphasia was the most common ICANS-related symptom reported, although the neurologic manifestations of ICANS were highly variable. Neuroimaging studies (magnetic resonance imaging or computed tomography) were often normal in cases of ICANS; however, electroencephalography often showed generalized background slowing, abnormal rhythmic, and periodic discharge patterns. The pooled mean (± SD) onset of ICANS was 6.4 ± 3.2 days, with a pooled mean duration of 8.3 ± 10.5 days. Two of the 23 studies (9%) reported 5 ICANS-related deaths among 233 participants. A subset of patients experienced persistent neurocognitive complaints at ≥1-year after CAR T cell therapy. The clinical presentation, onset, severity, long-term sequelae, and grading system of ICANS are variable. Future studies should consider using a consensus grading/reporting scale that would permit cross-trial comparisons of the safety profile of various CAR T cell products and enable the development of interventions to mitigate or manage these neurotoxicities. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This systematic review was conducted according to a published protocol (PROSPERO CRD42020207864) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) in systematic review reporting guidelines (Supplementary Table S1) [15,16].

Geriatric-assessment-identified functional deficits among adults with multiple myeloma with normal performance status.

OBJECTIVES: Findings from a brief geriatric assessment (GA) in a cohort of adults with multiple myeloma (MM) are presented, with particular attention to the utility of the GA in identifying important deficits in adults judged to have a normal Karnofsky Performance Status (KPS ≥ 80). MATERIALS AND METHODS: Adults age 18 and older with MM were recruited into an observational study from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) GA was administered at enrollment. Enrollees also completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Core 30 questionnaire (QLQ-C30), with subscales of physical, social, role, and cognitive functioning (range 0-100; higher values indicate better function). Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent KPS (score < 80 vs ≥ 80). RESULTS: Among 89 adults, the mean age was 69.1 years, 68% were aged ≥65 years, and 70% were white. In this cohort, 78% had KPS ≥ 80. Among those with KPS ≥ 80, functional impairments (Timed Up and Go ≥14 s and dependence in ≥1 instrumental activity of daily living) were seen in 30% and 21%, respectively, with 11% reporting ≥1 fall in the prior 6 months. At least two GA-identified deficits were detected in 50% of the overall cohort and in 41% of those with KPS ≥ 80. Among those with KPS ≥ 80, self-reported physical impairment on EORTC QLQ-C30 was noted by 34%. CONCLUSION: Using a modified CARG GA and EORTC questionnaire, functional impairments were identified among adults considered to have a good performance status based on a KPS (≥ 80). Future studies should focus on using GA measures for therapy assignment and identifying opportunities for intervening upon GA-identified deficits.

Longitudinal Analysis of Patient-Reported Cognitive Function in Multiple Myeloma.

BACKGROUND: Cancer-related cognitive impairment (CRCI) has been largely unstudied in patients with multiple myeloma (MM). This study describes patient-reported cognition over time and patient factors associated with adverse cognitive outcomes in MM. METHODS: Participants enrolled in a registry in which they completed a geriatric assessment at study entry, and 3 & 6 months after entry. Cognitive function was assessed using the EORTC QLQ-C30 Cognitive Function subscale, with CRCI defined as scores < 75. Generalized estimating equation (GEE) models were used to fit longitudinal models to investigate differences by group and differences in changes over time by group, with adjustment for time since diagnosis. RESULTS: One hundred and four adults with MM had mean age of 67 years and 30% identified as Black. Patient-reported CRCI was present in 18% of participants at enrollment, 21% at 3 months, and 30% at 6 months. Worse cognitive function was reported in those with impairments in physical function (P = .002), IADLs (P = .02), and performance status (P = .04), as well as in those who were prefrail/frail (P = .02) and depressed (P = .049). Greater cognitive decline over time was observed in patients without CRCI at enrollment (P < .0001) and those with lower levels of education (P = .04). CONCLUSION: This is one of the first studies to describe longitudinal changes in patient-reported cognition in patients with MM. Several potentially intervenable factors, including physical function impairment and depression, were associated with worse cognition at study entry, but only baseline CRCI status and education level were predictive of future decline.

Prevalence and clinical correlates of cognitive impairment in adults with plasma cell disorders.

INTRODUCTION: Older adults with plasma cell disorders (PCDs) experience cognitive dysfunction that may be attributable to the disease and associated therapies. Yet, this has seldom been reported in the literature. Our objectives were to describe cognitive function (objective and patient-reported) in adults with PCDs and to explore clinical correlates of cognitive impairment. MATERIALS AND METHODS: Participants completed a geriatric assessment between March 2018 and February 2020. Cognitive function was evaluated using two objective measures - Montreal Cognitive Assessment (MoCA, cutpoint <26) and Blessed Orientation Memory Concentration Test (BOMC, cutpoint >4) - and two patient-reported outcome (PRO) measures - Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF, cutpoint <45) and European Organization for Research and Treatment of Cancer Cognitive Functioning subscale (EORTC-CF, cutpoint <75). Spearman correlations examined relationships among these measures and log binomial regression was used to examine characteristics associated with cognitive impairment, as defined by the MoCA and PROMIS-CF measures. RESULTS: Among 86 participants with a mean age of 69 (range: 46-91), the prevalence of cognitive dysfunction was between 20% (BOMC) and 63% (MoCA). There was moderate correlation among objective measures (r = 0.51, p < 0.0001), moderate to high correlation among PRO measures (r = 0.69, p < 0.0001), but no correlation between objective and PRO measures. Factors associated with objective impairment included ≤ high school education (RR 1.46, p = 0.009), living alone (RR 1.42, p = 0.02), relapsed/refractory disease (RR 1.39, p = 0.04), empirically de-intensified induction therapy (RR 1.62, p = 0.008), frailty (RR 1.49, p = 0.04), and peripheral vascular disease (RR 1.54, p = 0.002). Factors associated with PRO impairment included social isolation (RR 3.43, p = 0.003), depression (RR 3.30, p = 0.004) and anxiety (RR 4.43, p = 0.0002), frailty (RR 3.60, p = 0.02), falls in the previous 6 months (RR 2.53, p = 0.02), and deficits in physical function (RR 4.44, p = 0.01). Older age was not associated with either objective or PRO impairment. DISCUSSION: Cognitive impairment, using objective and PRO screening measures, was relatively common in adults with PCDs. Cancer-related factors and medical comorbidities were associated with objective cognitive impairment whereas psychosocial and functional factors were associated with PRO impairment.