Understanding health outcome preferences of older adults diagnosed with multiple myeloma.

INTRODUCTION: Health outcome preferences of older adults with cancer vary based on burden/intensity of treatment and its impact on health outcomes such as survival, quality of life, and functional and cognitive well-being. We studied the association between age and health outcome preferences of adults with multiple myeloma (MM). MATERIALS AND METHODS: Using a single center prospective cohort study, we identified adults ≥50y with MM who underwent geriatric assessment (GA) within 30 days of initiating a new line of therapy. We assessed health outcome preferences using a nine-item health outcome preference scale where patients were asked to prioritize varying treatment outcomes in a Likert scale. We compared the response patterns for each item by age group (50-69y vs ≥70y) using Mantel-Haenszel chi-squared test. For items significant in bi-variable analysis, we built proportional odds models to study the association between age and health outcome preferences adjusting for sex, race, frailty, and high risk cytogenetics. RESULTS: We included 119 patients with a median age of 65y. Of these, 58% were male, 56% were non-Hispanic White, and 28% were frail. Older adults (≥70y) versus younger adults (50-69y) were more likely to prioritize health outcomes such as quality of life (53% vs. 34%), functional independence (74% vs. 33%), maintaining cognitive ability (79% vs. 54%), and living free from pain (50% vs 18%) over longer survival (all p values <0.05). In multivariable models, each one interquartile range (IQR) increase in age was associated with increased odds of prioritization of functional independence [adjusted odds ratio (aOR) 2.55, 95% confidence interval (CI) (1.44-4.53)], maintaining cognitive ability [aOR 1.75, 95% CI (1.01-3.02)], and willingness to take milder/ fewer treatments [aOR 2.40, 95% CI (1.36-4.26)] over longer survival. Similarly, each IQR increase in age was associated with decreased odds of prioritization of survival over quality of life [aOR 0.45, 95% CI (0.26-0.78)] and survival over being free from pain [aOR 0.39, 95% CI (0.22-0.69)]. DISCUSSION: Three out of four older adults (age ≥ 70y) with MM rated other outcomes, particularly functional and cognitive well-being, above survival. Determining the most significant treatment outcomes for older adults with MM can aid in establishing treatment goals and enhance shared decision-making.

Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

BACKGROUND: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. METHODS: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. RESULTS: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. CONCLUSIONS: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.

Low skeletal muscle mass and treatment outcomes among adults with haematologic malignancies: A systematic review and meta-analysis.

BACKGROUND: Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment-related toxicities among adults with haematologic malignancies remains unclear. METHODS: Using a pre-published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non-relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran's Q and the I2 statistic. All hypothesis testing was two-sided with an alpha of 0.05. RESULTS: Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B-cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48-2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28-2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34-2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I2 = 0.0%). CONCLUSIONS: LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.

Geriatric assessment-identified impairments and frailty in adults with cancer younger than 65: An opportunity to optimize oncology care.

INTRODUCTION: Frailty, a state of increased vulnerability to stressors due to aging or treatment-related accelerated aging, is associated with declines in physical, cognitive and/or social functioning, and quality of life for cancer survivors. For survivors aged <65 years, little is known about frailty status and associated impairments to inform intervention. We aimed to evaluate the prevalence of frailty and contributing geriatric assessment (GA)-identified impairments in adults aged <65 versus ≥65 years with cancer. MATERIALS AND METHODS: This study is a secondary analysis of clinical trial data (NCT04852575). Participants were starting a new line of systemic therapy at a community-based oncology private practice. Before starting treatment, participants completed an online patient-reported GA and the Physical Activity (PA) Vital Sign questionnaire. Frailty score and category were derived from GA using a validated deficit accumulation model: frail (>0.35), pre-frail (0.2-0.35), or robust (0-0.2). PA mins/week were calculated, and participants were coded as either meeting/not-meeting guidelines (≥90 min/week). We used Spearman (ρ) correlation to examine the association between age and frailty score and chi-squared/Fisher's-exact or ANOVA/Kruskal-Wallis statistic to compare frailty and PA outcomes between age groups. RESULTS: Participants (n = 96) were predominantly female (62%), Caucasian (68%), beginning first-line systemic therapy (69%), and 1.75 months post-diagnosis (median). Most had stage III to IV disease (66%). Common cancer types included breast (34%), gastrointestinal (23%), and hematologic (15%). Among participants <65, 46.8% were frail or pre-frail compared to 38.7% of those ≥65. There was no association between age and frailty score (ρ = 0.01, p = 0.91). Between age groups, there was no significant difference in frailty score (p = 0.95), the prevalence of frailty (p = 0.68), number of GA impairments (p = 0.33), or the proportion meeting PA guidelines (p = 0.72). However, older adults had more comorbid conditions (p = 0.03) and younger adults had non-significant but clinically relevant differences in functional ability, falls, and PA level. DISCUSSION: In our cohort, the prevalence of frailty was similar among adults with cancer <65 when compared to those older than 65, however, types of GA impairments differed. These results suggest GA and the associated frailty index could be useful to identify needs for intervention and inform clinical decisions during cancer treatment regardless of age. Additional research is needed to confirm our findings.

Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk.

In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10-5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high-risk disease (≥2 HRCAs). Video Abstract.

Racial differences in body composition and survival among older adults with gastrointestinal malignancies.

INTRODUCTION: Muscle and adipose tissue measures can be quantified from routinely obtained computed tomography (CT) images and are predictors of chemotherapy-related toxicities and survival among patients with gastrointestinal (GI) malignancies. Most studies to date have consisted of predominantly White patients, and the role of body composition among minoritized racial groups is unknown. We examined racial differences in body composition and survival among patients with GI malignancies. MATERIALS AND METHODS: This was a prospective cohort study of patients with GI malignancies. Single slices of axial CT images from L3 segments were analyzed using Slice-O-Matic software. The skeletal muscle area (cm2) was divided by height to obtain the skeletal muscle index (SMI, cm2/m2). Skeletal muscle radiodensity (SMD) in Hounsfield units (HU) was used for muscle composition. We compared body composition parameters between non-Hispanic (NH)-White and NH-Black participants. Cox models were used to examine the impact of body composition on survival. We proposed new race-specific cutoffs for body composition using optimal stratification. RESULTS: Five hundred forty patients were included, of which 24% were NH-Black. In Cox models stratified by race, each 5 cm2/m2 decrease in SMI was associated with increase in risk of all-cause mortality in NH-Black patients (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.04-1.49 p = 0.02). With the existing cut points, neither sarcopenia nor myosteatosis was associated with worse survival. Using a new cutoff for sarcopenia in NH-Black patients, NH-Black patients with sarcopenia (HR 2.31 95%CI 1.10-4.88 p = 0.03) and myosteatosis (HR 2.63 95% CI 1.25-5.53 p = 0.01) had worse survival. DISCUSSION: NH-Black older patients with GI cancers and sarcopenia or myosteatosis have worse overall survival.

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.

The association between food access and frailty among older adults with gastrointestinal malignancies-The CARE Registry.

BACKGROUND: Food access is associated with higher gastrointestinal (GI) cancer mortality; however, its association with frailty, which is a predictor of premature mortality among older adults with cancer, is less understood. METHODS: The authors included 880 adults aged 60 years and older who were recently diagnosed with GI cancers and were undergoing self-reported geriatric assessment at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. Food access was measured using the 2019 US Department of Agriculture Economic Research Service designation low-income, low-access (LILA), classifying census tracts based on income and/or access to food stores at various distances. The primary outcome was frailty on the CARE (Cancer and Aging Resilience Evaluation) Frailty Index, a composite of the proportion of impaired geriatric assessment measures. The authors examined the LILA-frailty association with modified Poisson regression accounting for census-tract clustering. RESULTS: The median patient age was 69 years, 58.1% were men, 22.5% were non-Hispanic Black, 29.2% had colorectal cancer, 28.0% had pancreatic cancer, 70.1% presented with stage III/IV disease, and 34.9% were frail. A higher proportion in LILA areas were non-Hispanic Black (44.1% vs. 10.8%; p < .001) and had less education (high school or less: 48.1% vs. 37.9%; p = .020). Adjusting for age, race and ethnicity, sex, cancer type and stage, and education, an LILA designation was associated with 58% greater odds of worsening frailty status (95% confidence interval, 1.18-2.12). An analysis of LILA subcategories revealed that associations were maintained across all LILA measures. CONCLUSIONS: Poor food access was associated with a greater risk of frailty among newly diagnosed older adults with GI cancers before they received systemic treatment. Intervening on local food access, particularly in LILA areas, may be a target for improving rates of frailty and promoting health equity in this population.

Management of Older Adults With Colorectal Cancer: The Role of Geriatric Assessment.

Older adults share a growing burden of cancer morbidity and mortality. This is present across the spectrum of oncologic diagnoses and is particularly true with colorectal cancer (CRC), where older adults continue to share the burden of diagnoses. However, optimal cancer treatment decision making in older adults remains a significant challenge, as the majority of previous clinical trials shaping the current treatment landscape have focused on younger patients, often with more robust performance status and fewer medical comorbid conditions. The heterogeneous aging process of older adults with CRC necessitates a personalized treatment approach, as approximately three-quarters of older adults with CRC also have a concominant geriatric syndrome and more than half of older adults with CRC are pre-frail or frail. Treatment decisions shoud be multifaceted, including consultation with the patient and their familes regarding their wishes, with consideration of the patient's quality of life, functional status, medical comorbid conditions, social support, and treatment toxicity risk. Geriatric assessment is a systematic and validated approach to assess an older adults's potential strengths and vulnerabilities, which can in turn be used to assist with comprehensive cancer care planning and support. In this review, we will summarize current treatment approaches for older adults with CRC, with a particular focus on the incorporation of the geriatric assessment.

SARC-F as a screening tool to detect computed tomography-based sarcopenia and myosteatosis among older adults with cancer.

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) recommends SARC-F as a tool for identifying sarcopenia among older adults. However, the role of SARC-F among older adults with cancer remains unexplored. We aimed to evaluate the diagnostic utility of SARC-F to identify those with sarcopenia, or low muscle mass (using skeletal muscle index [SMI]), and myosteatosis (using skeletal muscle density [SMD]) from computed tomography (CT) imaging and the association of SARC-F with all-cause mortality. METHODS: Older adults (≥60 years) presenting for initial consultation at UAB medical oncology clinic who underwent geriatric assessment were enrolled in a prospective cohort study. We identified study participants who completed SARC-F screening and had available CT imaging within 60 days of study enrollment. Using single-slice CT images at the L3 vertebral level, we computed SMI and SMD using published methods. Sarcopenia and myosteatosis were defined using published cutpoints. We calculated the sensitivity and specificity of SARC-F for detecting low muscle mass and low muscle density using published thresholds. Finally, we computed the impact of SARC-F and CT measures on overall survival using Kaplan-Meier curves and Cox regression models, after adjusting for age, sex, cancer type, and cancer stage. RESULTS: We identified 212 older adults with a median age of 68.8 years; with 60.8% males, 76.6% whites, and pancreatic cancer (21.2%) being the most common malignancy. In the overall cohort, 30.7% had abnormal SARC-F using published cutpoints. SARC-F ≥ 4 had a sensitivity of 35% and a specificity of 76% to identify low muscle mass. SARC-F ≥ 4 had a sensitivity of 38% and a specificity of 74% to identify low muscle density. Those with SARC-F ≥ 4 and low SMI/SMD had worse survival compared to those with low SMI/SMD alone. Incorporating SARC-F improved survival prognostication beyond SMI and SMD (HR = 3.1; p < 0.001; Harrel's C from 0.73 to 0.76). CONCLUSIONS: SARC-F as a screening tool has limited diagnostic utility for identifying older adults with low muscle mass and/or density. However, SARC-F retains prognostic value independent of CT-based muscle measures in predicting mortality among older adults with cancer.

Implementation of the Web-Enabled Cancer & Aging Resilience Evaluation (WeCARE) in an outpatient oncology setting.

INTRODUCTION: Although geriatric assessments (GAs) are recommended for use in older adults with cancer, their integration into oncology practice remain suboptimal. Here, we report our experience integrating web-enabled GA (WeCARE) into oncology practice as an augmented delivery method and provider interface format to overcome implementation barriers. MATERIALS AND METHODS: Older patients (≥60 years) with a gastro-intestinal (GI) malignancy presenting for an initial visit to medical oncology clinic at a single institution between December 7, 2021 and October 10, 2022 were contacted by staff two days in advance of their visits and sent a link to the WeCARE GA, rather than the paper version used previously. Results were directly embedded into the medical record. We describe our initial implementation outcomes and the results of a provider usability survey. RESULTS: Of 266 eligible patients, 221 (83.1%) were successfully contacted by telephone and 200 (75.2%) completed the WeCARE prior to their appointment. More than one phone call was required to make contact for 35.7% of patients, with a mean duration of phone conversation of 2.8 min. Most patients preferred email delivery to text (63% vs 31%); 4.5% were unable to access surveys due to inadequate technology, and 25.7% brought up additional logistical concerns. Among GI oncology providers surveyed, all six found the WeCARE tool and dashboard acceptable, appropriate, and feasible. However, only a third of providers often or always used the dashboard to inform treatment decisions and guide interventions. DISCUSSION: With nearly three-quarters of patients completing the WeCARE prior to their visits with minimal staff support and time required, this method of administration may be a viable format to overcome barriers to GA implementation. Additional work is needed to integrate the results meaningfully into clinical practice.

In-Clinic versus Hybrid Cancer Rehabilitation Service Delivery during the COVID-19 Pandemic: An Outcome Comparison Study.

Diminished health-related quality of life (HRQOL) is common among cancer survivors but often amendable to rehabilitation. However, few access real-world rehabilitation services. Hybrid delivery modes (using a combination of in-clinic and synchronous telehealth visits) became popular during the COVID-19 pandemic and offer a promising solution to improve access beyond the pandemic. However, it is unclear if hybrid delivery has the same impact on patient-reported outcomes and experiences as standard, in-clinic-only delivery. To fill this gap, we performed a retrospective, observational, comparative outcomes study of real-world electronic medical record (EMR) data collected by a national outpatient rehabilitation provider in 2020-2021. Of the cases meeting the inclusion criteria (N = 2611), 60 were seen to via hybrid delivery. The outcomes evaluated pre and post-rehabilitation included PROMIS® global physical health (GPH), global mental health (GMH), physical function (PF), and the ability to participate in social roles and activities (SRA). The patient experience outcomes included the Net Promoter Survey (NPS®) and the Select Medical Patient-Reported Experience Measure (SM-PREM). A linear and logistic regression was used to examine the between-group differences in the PROMIS and SM-PREM scores while controlling for covariates. The hybrid and in-clinic-only cases improved similarly in all PROMIS outcomes (all p < 0.05). The association between the delivery mode and the likelihood of achieving the minimal important change in the PROMIS outcomes was non-significant (all p > 0.05). No between-group differences were observed in the NPS or SM-PREM scores (all p > 0.05). Although more research is needed, this real-world evidence suggests that hybrid rehabilitation care may be equally beneficial for and acceptable to cancer survivors and supports calls to expand access to and reimbursement for telerehabilitation.

Anxiety is Associated With Geriatric Assessment Impairments and Reduced Quality of Life Among Older Adults With Colorectal Cancer: Results From the CARE Registry.

BACKGROUND: Colorectal cancer (CRC) preferentially affects older adults. Modifiable factors, such as anxiety, can be measured as part of cancer-specific geriatric assessments (GA) completed prior to the start of treatment. We hypothesized that anxiety is prevalent among older adults with CRC and is associated with increased depression, increased frailty, and impaired health-related quality of life (HRQOL). PATIENTS AND METHODS: Patients ≥60 years old with newly diagnosed CRC completed a cancer-specific GA called the Cancer and Aging Resilience Evaluation (CARE). Between September 2017 and February 2023, we analyzed patients with CRC who had not yet received any systemic treatment. Anxiety was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4-item short form and reported as t-scores. We used modified Poisson models with robust variance estimation to assess for differences in the prevalence of depression, frailty, and impaired HRQOL. RESULTS: We analyzed 277 older adults with CRC. The median age of the study sample was 68 years. 57% were male, 72% were non-Hispanic White, and most had advanced CRC (35% stage III and 39% stage IV). Moderate/severe anxiety was present in 17% of older adults with newly diagnosed CRC. In adjusted models, as compared to patients without moderate/severe anxiety, patients with moderate/severe anxiety had significantly increased risk of depression (prevalence ratio [PR] 7.60, CI 4.90-11.78), frailty (PR 4.93, CI 3.01-8.07), impaired physical HRQOL (PR 3.57, CI 2.03-6.28), and impaired mental HRQOL (PR 3.82, CI 2.12-6.89). CONCLUSION: Among older adults with CRC, anxiety is associated with increased depression and frailty as well as reduced HRQOL.

Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial.

BACKGROUND: For patients with newly diagnosed multiple myeloma, reaching minimal residual disease (MRD) negativity after treatment is associated with improved outcomes; however, the use of MRD to modulate therapy remains elusive. We present the final analysis of the MASTER trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) therapy in patients with newly diagnosed multiple myeloma, in which MRD status is used to modulate treatment duration and cessation. METHODS: MASTER was a multicentre, single-arm, phase 2 trial conducted in five academic medical centres in the USA. Eligible participants were 18 years or older with newly diagnosed multiple myeloma (measurable by serum or urine protein electrophoresis or serum free light chains), a life expectancy of at least 12 months, and an Eastern Cooperative Oncology Group performance status of 0-2, and had received no previous treatment for multiple myeloma except up to one cycle of therapy containing bortezomib, cyclophosphamide, and dexamethasone. The study was enriched for participants with high-risk chromosome abnormalities (HRCAs). During the induction phase, participants received four 28-day cycles of Dara-KRd, each comprising daratumumab (16 mg/kg intravenously on days 1, 8, 15, and 22), carfilzomib (56 mg/m2 intravenously on days 1, 8, and 15), lenalidomide (25 mg orally on days 1-21), and dexamethasone (40 mg orally or intravenously on days 1, 8, 15, and 22); induction was followed by autologous haematopoietic stem-cell transplantation and up to two phases of consolidation with Dara-KRd. We assessed MRD by next-generation sequencing after or during each phase. The primary endpoint was reaching MRD negativity (<10-5). Participants who reached MRD negativity after or during two consecutive phases stopped treatment and began observation with MRD surveillance (MRD-SURE); participants who did not reach two consecutive MRD-negative results received maintenance lenalidomide. Secondary endpoints included progression-free survival and cumulative incidence of progression. All analyses were conducted in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03224507, and is complete. FINDINGS: Between Mar 21, 2018, and Oct 23, 2020, 123 participants were recruited to the study, of whom 70 (57%) were men, 53 (43%) were women, 94 (76%) were non-Hispanic White, 25 (20%) were non-Hispanic Black, and four (3%) were of another race or ethnicity. The median age of participants was 61 years (IQR 55-68), and 24 (20%) were aged 70 years or older. The median duration of follow up was 42·2 months (IQR 34·5-46·0). Of the 123 participants, 53 (43%) had no HRCAs, 46 (37%) had one HRCA, and 24 (20%) had two or more HRCAs. For 118 (96%) of 123 participants, MRD was evaluable by next-generation sequencing; the remaining five had an absence of sufficiently unique clonogenic sequences to enable tracking by the assay. Of these 118 participants, 96 (81%, 95% CI 73-88) reached MRD of less than 10-5 (comprising 39 [78%, 64-88] of 50 participants with no HRCAs, 38 [86%, 73-95] of 44 participants with one HRCA, and 19 [79%, 58-93] of 24 participants with two or more HRCAs) and 84 (71%, 62-79) reached MRD-SURE and treatment cessation. 36-month progression-free survival among all 123 participants was 88% (95% CI 78-95) for participants with no HRCAs, 79% (67-88) for those with one HRCA, and 50% (30-70) for those with two or more HRCAs. For the 84 participants reaching MRD-SURE, the 24-month cumulative incidence of progression from cessation of therapy was 9% (95% CI 1-19) for participants with no HRCAs, 9% (1-18) for those with one HRCA, and 47% (23-72) for those with two or more HRCAs. 61 participants (comprising 52% of 118 MRD-evaluable participants and 73% of 84 participants who reached MRD-SURE) remain free of therapy and MRD-negative as of Feb 7, 2023. The most common grade 3-4 adverse events were neutropenia (43 patients, 35%), lymphopenia (28 patients, 23%), and hypertension (13 patients, 11%). Three treatment-emergent deaths were recorded: two sudden deaths and one due to viral infection, none of which were judged to be treatment-related. INTERPRETATION: This approach provided positive outcomes and a pathway for treatment cessation in most patients with newly diagnosed multiple myeloma. Outcomes for patients with ultra-high-risk multiple myeloma, defined as those with two or more HRCAs, remain unsatisfactory, and these patients should be prioritised for trials with early introduction of therapies with novel mechanisms of action. FUNDING: Amgen and Janssen Pharmaceuticals.

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia.

BACKGROUND: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry- and claims-based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. METHODS: We identified 4010 older adults (aged 66-99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population-based cohort study using the Surveillance, Epidemiology, and End Results-Medicare database with median follow-up of 3.92 (interquartile range: 2.58-5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. RESULTS: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all-cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64-0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51-0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49-0.66, p < 0.01) as well as in PV and ET subgroups. CONCLUSIONS: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET.

Humoral immune reconstitution following therapy with daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd), autologous hematopoietic cell transplantation, and measurable residual disease-response-adapted treatment cessation.

Quadruplet induction, autologous hematopoietic cell transplant (AHCT), and measurable residual disease (MRD) response-adapted consolidation yield an unprecedented depth of response in newly diagnosed multiple myeloma. Patients treated on MASTER (NCT03224507) ceased therapy and entered active surveillance (MRD-SURE) after achieving MRD negativity. This study characterizes quantitative changes in the immunoglobulin (Ig) gene repertoire by next-generation sequencing and serum gamma globulin levels. Quadruplet therapy leads to profound hypogammaglobulinemia and reduction in the Ig gene repertoire. Immune reconstitution (IR) is delayed in patients who received post-AHCT consolidation compared to those who do not. Eighteen months after treatment cessation, there was no statistically significant difference between the groups.

Association of emotional support with quality of life, mental health, and survival in older adults with gastrointestinal malignancies-Results from the CARE registry.

BACKGROUND: Emotional support (ES) is the most frequently reported support need among older adults with cancer. Yet, the association of ES with cancer outcomes is largely unknown. This study examined the association of ES with health-related quality of life (HRQoL), mental health, and survival among older adults with gastrointestinal (GI) malignancies. METHODS: We included newly diagnosed older adults (≥60 years) with GI cancer undergoing self-reported geriatric assessment at their first clinic visit. ES was measured using an adaptation of the Medical Outcomes Study (dichotomized adequate ES vs. inadequate ES). Outcomes included physical and mental HRQoL, anxiety, depression, and survival. Multivariable linear regression evaluated the association between ES and HRQoL scores. Multivariable logistic regression evaluated the association of ES with anxiety and depression. All models were adjusted for age at geriatric assessments, race, sex, and cancer type/stage. RESULTS: 795 participants were included. Median patient age was 68 years (IQR: 64-74), 58% were male, and most cancers were either colorectal (37.9%) or pancreatic (30.8%). Most (77.6%) had adequate ES. Patients with inadequate ES were more likely to be Black (31.5 vs. 20.8%, p = 0.005), disabled (24.1 vs. 10.4%, p < 0.001), widowed/divorced (54.2 vs. 24.8%, p < 0.001) and had lower physical and mental HRQoL t-scores (Physical ß: -3.35, 95% CI: -5.25, -1.46; Mental ß: -2.46, 95% CI: -4.11, -0.81) and higher odds of depression (aOR: 2.22, CI: 1.34-3.69). This study found no difference between those with adequate ES versus inadequate ES in the proportion of deaths within 1 year of diagnosis (24.3% vs. 24.2%, p = 0.966), or within 2 years of diagnosis (32.4% vs. 33.2%, p = 0.126). CONCLUSIONS: Older adults with inadequate ES have worse physical and mental HRQoL and higher odds of depression compared to those with adequate ES.

Association of unmet basic resource needs with frailty and quality of life among older adults with cancer-Results from the CARE registry.

BACKGROUND: Basic resource needs related to transportation, housing, food, and medications are important social determinants of health and modifiable indicators of poverty, but their role in modifying the risk of frailty and health-related quality of life (HRQoL) remains unknown. The goal of our study was to examine the prevalence of unmet basic needs and their association with frailty and HRQoL in a cohort of older adults with cancer. METHODS: The CARE registry prospectively enrolls older adults (≥60 years) with cancer. Assessments of transportation, housing, and material hardship were added to the CARE tool in 8/2020. The 44-item CARE Frailty Index was used to define frailty, and subdomains of physical and mental HRQoL were assessed using the PROMIS® 10-global. Multivariable analysis examined the association between unmet needs with frailty and HRQoL subdomains, adjusting for covariates. RESULTS: The cohort included 494 participants. Median age of 69 years, 63.6% were male and 20.2% were Non-Hispanic (NH) Black. Unmet basic needs were reported in 17.8% (transportation 11.5%, housing 2.8%, and material hardship 7.5%). Those with unmet needs were more often NH Black (33.0% vs. 17.8%, p = 0.006) and less educated (