Search

PURPOSE Representativeness in acute leukemia clinical research is essential for achieving health equity. The National Cancer Institute's mandate for Comprehensive Cancer Centers (CCCs) to define and assume responsibility for cancer control and treatment across a geographic catchment area provides an enforceable mechanism to target and potentially remediate participatory inequities. METHODS We examined enrollee characteristics across 15 Cancer and Leukemia Group B/Alliance cooperative group adult acute leukemia clinical trials (N = 3,734) from 1998 to 2013, including participation in optional companion biobanks. We determined enrollment odds by race-ethnicity for all participants adjusted for national incidence, and for those enrolled at CCCs adjusted for catchment area incidence. We modeled biobank participation by sociodemographics using logistic regression. RESULTS Non-Hispanic (NH)-White patients were more likely to be enrolled than NH-Black, NH-Asian, or Hispanic patients (odds ratio [OR], 0.75, 0.48, and 0.44, respectively; all P < .001), but less likely than NH-Native American patients (OR, 1.91; P < .001), adjusted for national incidence. Enrollment odds were lower for NH-Black, NH-Asian, and Hispanic patients at CCCs adjusted for catchment area incidence (OR, 0.57, 0.26, and 0.32, respectively; P < .001); differences were driven by overenrollment of NH-White patients from outside self-defined catchment areas (18.1% v 12.3%; χ2 P = .01) and by CCCs with less absolute enrollee diversity (rank sum P = .03). Among all enrollees, NH-White race-ethnicity and lower neighborhood deprivation correlated with biobank participation (OR, 1.81 and 1.45, respectively; P = .01 and .03). For CCC enrollees, the correlation of race-ethnicity with biobank participation was attenuated by a measure accounting for their site's degree of enrollment disparity but not neighborhood deprivation. CONCLUSION Acute leukemia clinical research disparities are substantial and driven by structural trial enrollment barriers at CCCs. Real-time CCC access and enrollment monitoring is needed to better align research participation with local populations.

Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the heterogeneous composition of these diseases has limited our understanding of these domains. The NHLBI-sponsored MDS Natural History Study (NCT02775383) is a prospective cohort enrolling patients undergoing diagnostic work up for suspected MDS or MDS/myeloproliferative neoplasms (MPNs) in the setting of cytopenias. Untreated patients undergo bone marrow assessment with central histopathology review for assignment as MDS, MDS/MPN, idiopathic cytopenia of undetermined significance (ICUS), acute myeloid leukemia (AML) with

PURPOSE Advances in digital health technology can overcome barriers to measurement of function and mobility for older adults with blood cancers, but little is known about how older adults perceive such technology for use in their homes. METHODS To characterize potential benefits and barriers associated with using technology for home functional assessment, we conducted three semistructured focus groups (FGs) in January 2022. Eligible patients came from the Older Adult Hematologic Malignancies Program at Dana-Farber Cancer Institute (DFCI), which includes adults 73 years and older enrolled during their initial consult with their oncologist. Eligible caregivers were 18 years and older and identified by enrolled patients as their primary caregiver. Eligible clinicians were practicing DFCI hematologic oncologists, nurse practitioners, or physician assistants with ≥2 years of clinical experience. A qualitative researcher led thematic analysis of FG transcripts to identify key themes. RESULTS Twenty-three participants attended the three FGs: eight patients, seven caregivers, and eight oncology clinicians. All participants valued function and mobility assessments and felt that technology could overcome barriers to their measurement. We identified three themes related to potential benefits: making it easier for oncology teams to consider function and mobility; providing standardized, objective data; and facilitating longitudinal data. We also identified four themes related to barriers to home functional assessment: concerns related to privacy and confidentiality, burden of measuring additional patient data, challenges in operating new technology, and concerns related to data improving care. CONCLUSION These data suggest that specific concerns raised by older patients, caregivers, and oncology clinicians must be addressed to improve acceptability and uptake of technology used to measure function and mobility in the home.

The National Heart, Lung, and Blood Institute National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling cytopenic patients with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1,298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy, or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel two-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best (1) predict a diagnosis of myeloid malignancy and (2) within those with a predicted myeloid malignancy, predict whether they had MDS. The classifier achieved a PPV of 0.84 and NPV of 0.8 with an AUROC of 0.85 when classifying patients as myeloid vs. no myeloid malignancy based on VAFs in 17 genes and a PPV of 0.71 and NPV of 0.64 with an AUROC of 0.73 when classifying patients as MDS vs. non-MDS malignancy based on VAFs in 10 genes. We next assessed how this approach could complement histopathology to improve diagnostic accuracy. For 99 of 139 (71%) patients (PPV of 0.83 and NPV of 0.65) with local and centralized histopathologic disagreement in myeloid vs. no myeloid malignancy, the classifier-predicted diagnosis agreed with the tertiary pathology review (considered the internal gold standard). An online version of the classifier that can be used with either VAFs or binary mutation profiles is available at https://thenationalmdsstudy.net.

Older patients with cancer often receive treatment regimens based on their age without considering other objective factors that may influence outcomes. Assessment of frailty can identify older patients who are robust and therefore more likely to benefit from intensive treatment, or conversely, frail and might instead be offered alternative approaches. However, such assessment requires specialised training and dedicated clinical resources. Alternative quantitative biomarkers associated with frailty are lacking. Here, we asked if expression signatures of 74 immune cell, ageing, and senescence-related messenger RNAs in purified peripheral blood T cells could identify associations with clinical frailty in patients with haematological malignancies. We studied 69 patients between the ages of 36 and 92 years (median 76 years) with leukaemia, lymphoma, or multiple myeloma, across two institutions. Expression of four genes (aryl hydrocarbon receptor [AHR], CD27, CD28, and interleukin-2 receptor subunit alpha [IL2RA; CD25]) in T cells was associated with frailty, independent of age. An expression-based regression model had 76% sensitivity and 90% specificity to assign a patient as robust. These data identify measurable peripheral blood correlates of clinical frailty and suggest biomarkers for future prospective assessment.

PURPOSE The terms undertreatment and overtreatment are often used to describe inappropriate management of older adults with cancer. We conducted a comprehensive scoping review of the literature to clarify the meanings behind the use of the terms. METHODS We searched PubMed (National Center for Biotechnology Information), Embase (Elsevier), and CINAHL (EBSCO) for titles and abstracts that included the terms undertreatment or overtreatment with regard to older adults with cancer. We included all types of articles, cancer types, and treatments. Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived through qualitative analysis. Within a random subset of articles, C.D. and K.P.L. independently performed this analysis to determine final categories and then independently assigned these categories to assess inter-rater reliability. RESULTS Articles using the terms undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion in our review (n = 256). Only 14 articles (5.5%) explicitly provided formal definitions; for the remaining, we inferred the implicit definitions from the terms’ surrounding context. There was substantial agreement (κ = 0.81) between C.D. and K.P.L. in independently assigning categories of definitions within a random subset of 50 articles. Undertreatment most commonly implied less than recommended therapy (148; 62.7%) or less than recommended therapy associated with worse outcomes (88; 37.3%). Overtreatment most commonly implied intensive treatment of an older adult in whom the harms of treatment outweigh the benefits (38; 53.5%) or intensive treatment of a cancer not expected to affect an older adult in his/her remaining lifetime (33; 46.5%). CONCLUSION Undertreatment and overtreatment of older adults with cancer are imprecisely defined concepts. We propose new, more rigorous definitions that account for both oncologic factors and geriatric domains.

Background:Polypharmacy and potentially inappropriate medications (PIMs) are common among older adults with blood cancers, but their association with frailty and how to manage them optimally remain unclear.Patients and Methods:From 2015 to 2019, patients aged ≥75 years presenting for initial oncology consult underwent screening geriatric assessment. Patients were determined to be robust, prefrail, or frail via deficit accumulation and phenotypic approaches. We quantified each patient’s total number of medications and PIMs using the Anticholinergic Risk Scale (ARS) and a scale we generated using the NCCN Medications of Concern called theGeriatric Oncology Potentially Inappropriate Medications(GO-PIM) scale. We assessed cross-sectional associations of PIMs with frailty in multivariable regression models adjusting for age, gender, and comorbidity.Results:Of 785 patients assessed, 603 (77%) were taking ≥5 medications and 421 (54%) were taking ≥8 medications; 201 (25%) were taking at least 1 PIM based on the ARS and 343 (44%) at least 1 PIM based on the GO-PIM scale. Among the 468 (60%) patients on active cancer treatment, taking ≥8 medications was associated with frailty (adjusted odds ratio [aOR], 2.82; 95% CI, 1.92–4.17). With each additional medication, the odds of being prefrail or frail increased 8% (aOR, 1.08; 95% CI, 1.04–1.12). With each 1-point increase on the ARS, the odds of being prefrail or frail increased 19% (aOR, 1.19; 95% CI, 1.03–1.39); with each additional PIM based on the GO-PIM scale, the odds increased 65% (aOR, 1.65; 95% CI, 1.34–2.04).Conclusions:Polypharmacy and PIMs are prevalent among older patients with blood cancers; taking ≥8 medications is strongly associated with frailty. These data suggest careful medication reconciliation for this population may be helpful, and deprescribing when possible is high-yield, especially for PIMs on the GO-PIM scale.

We undertook a cross-sectional survey of a random sample of thoracic oncologists from the American Society of Clinical Oncology clinical directory to characterize whether prognostic uncertainty has increased and if tolerance of uncertainty is associated with prognostic discussion practices. We also assessed the Physicians’ Reactions to Uncertainty Scale and presented a vignette about an incurable patient with uncertain life expectancy. One hundred and ninety-two of 438 surveys (43.8%) were received. Of the respondents, 52.1% agreed “there is more prognostic uncertainty in the management of lung cancer now than 10 years ago,” and 37.4% noted difficulty “staying up-to-date.” In multivariable analyses, physician-reported anxiety about uncertainty (p = .05) and reluctance to disclose uncertainty (p = .04) were inversely associated with reporting having prognostic discussions with most patients. For the vignette, 92.1% reported they would discuss incurability, but only 76.3% said they would discuss the patient's life expectancy. Our data suggest prognostic uncertainty has increased in thoracic oncology and oncologists’ tolerance of uncertainty may affect discussion practices.

Background: Although blood cancers are accompanied by a high level of prognostic uncertainty, little is known about when and how hematologic oncologists discuss prognosis. Objectives: Characterize reported practices and predictors of prognostic discussions for a cohort of hematologic oncologists. Design: Cross-sectional mailed survey in 2015. Setting/Subjects: U.S.-based hematologic oncologists providing clinical care for adult patients with blood cancers. Measurements: We conducted univariable and multivariable analyses assessing the association of clinician characteristics with reported frequency of initiation of prognostic discussions, type of terminology used, and whether prognosis is readdressed. Results: We received 349 surveys (response rate = 57.3%). The majority of respondents (60.3%) reported conducting prognostic discussions with “most” (>95%) of their patients. More than half (56.8%) preferred general/qualitative rather than specific/numeric terms when discussing prognosis. Although 91.3% reported that they typically first initiate prognostic discussions at diagnosis, 17.7% reported routinely never readdressing prognosis or waiting until death is imminent to revisit the topic. Hematologic oncologists with ≤15 years since medical school graduation (odds ratio [OR] 0.51; confidence interval (95% CI) 0.30–0.88) and those who considered prognostic uncertainty a barrier to quality end-of-life care (OR 0.57; 95% CI 0.35–0.90) had significantly lower odds of discussing prognosis with “most” patients. Conclusions: Although the majority of hematologic oncologists reported discussing prognosis with their patients, most prefer general/qualitative terms. Moreover, even though prognosis evolves during the disease course, nearly one in five reported never readdressing prognosis or only doing so near death. These findings suggest the need for structured interventions to improve prognostic communication for patients with blood cancers.

Background/objectives Cancer-focused organizations now recommend routine assessment of instrumental activities of daily living (iADLs) for all older patients with cancer, along with assessment of basic activities of daily living (ADLs) if possible. However, little is known regarding the role of iADLs in predicting survival and acute-care utilization in populations of older adults with different hematologic malignancies. Design Prospective cohort study. Setting and participants A screening geriatric assessment was conducted for adults 75 years and older with hematologic malignancies (n = 464) presenting for initial consultation at a large tertiary cancer hospital in Boston, MA. Measurements Univariable and multivariable analyses assessed the association of dependency in ADLs and dependency in iADLs with survival and care utilization (emergency department [ED] visits and unplanned hospitalizations). Results Subjects were a mean age of 79.7 years and had a mean follow-up of 13.8 months. Overall, 11.4% had dependency in ADLs and 26.7% had dependency in iADLs. Only iADL dependency was associated with higher mortality (hazard ratio = 2.34 [95% confidence interval [CI] = 1.46-3.74]) independently of age, comorbidity, cancer aggressiveness, and treatment intensity. The effect was dose dependent, and impairments in shopping, meal preparation, and housework were all independently associated with a higher hazard of death. iADL dependency was also associated with higher odds of ED visits (odds ratio [OR] = 2.76 [95% CI = 1.30-5.84]) and hospitalizations (OR = 2.89 [95% CI = 1.37-6.09]). Several geriatric domain impairments, including probable cognitive impairment and physical dysfunction, were associated with iADL dependency. Conclusion These findings suggest that older adults with hematologic malignancies and iADL dependency experience higher mortality and acute-care utilization, arguing that iADLs should be formally assessed as part of routine oncology care. J Am Geriatr Soc 67:889-897, 2019.

Older patients with AML face difficult treatment decisions as they can be treated either with ‘intensive’ chemotherapy requiring prolonged hospitalization, or ‘non-intensive’ chemotherapy. Although clinicians often perceive intensive chemotherapy as more burdensome, research is lacking on patients’ quality of life (QOL) and psychological distress. We conducted a longitudinal study of older patients (≥60 years) newly diagnosed with AML receiving intensive (cytarabine/anthracycline combination) or non-intensive (hypomethylating agents) chemotherapy. We assessed patients’ QOL [Functional-Assessment-of-Cancer-Therapy-Leukemia] and psychological distress [Hospital-Anxiety-and-Depression-Scale] at baseline and 2, 4, 8, 12, and 24 weeks after diagnosis. We enrolled 75.2% (100/133) of eligible patients within 72-hours of initiating intensive (n = 50) or non-intensive (n = 50) chemotherapy. Patient QOL improved over time (β = 0.32, P = 0.013). At baseline, 33.3% (33/100) and 30.0% (30/100) of patients reported clinically significant depression and anxiety symptoms, respectively, with no differences between groups. Patients’ depression symptoms did not change over time, while their anxiety symptoms decreased over time (β = −0.08, P

For patients with blood cancers, comorbid mental health disorders at diagnosis likely affect the entire disease trajectory, as they can interfere with disease information processing, lead to poor coping, and even cause delays in care. We aimed to characterize the prevalence of depression and anxiety in patients with blood cancers. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients ≥67 years old diagnosed with lymphoma, myeloma, leukemia, or myelodysplastic syndromes between 2000 and 2015. We determined the prevalence of precancer depression and anxiety and cancer-associated (CA) depression and anxiety using claims data. We identified factors associated with CA-depression and CA-anxiety in multivariate analyses. Among 75 691 patients, 18.6% had at least 1 diagnosis of depression or anxiety. Of the total cohort, 13.7% had precancer depression and/or precancer anxiety, while 4.9% had CA-depression or CA-anxiety. Compared with patients without precancer anxiety, those with precancer anxiety were more likely to have subsequent claims for CA-depression (odds ratio [OR] 2.98; 95% CI 2.61-3.41). Other factors associated with a higher risk of CA- depression included female sex, nonmarried status, higher comorbidity, and myeloma diagnosis. Patients with precancer depression were significantly more likely to have subsequent claims for CA-anxiety compared with patients without precancer depression (OR 3.01; 95% CI 2.63-3.44). Female sex and myeloma diagnosis were also associated with CA-anxiety. In this large cohort of older patients with newly diagnosed blood cancers, almost 1 in 5 suffered from depression or anxiety, highlighting a critical need for systematic mental health screening and management for this population.

Background: Frailty is associated with poor tolerance to chemotherapy and mortality. While recent evidence suggests measures of frailty such as gait speed predict survival in older patients with hematologic malignancies such as lymphoma (Liu, Blood, 2019), its predictive ability has not been compared to disease-based prognostic risk scores. Methods: From February 2015 to April 2019, all patients aged 75 years and older who presented for initial consultation for at the Dana-Farber Cancer Institute for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Waldenstrom macroglobulinemia (WM) were approached for a screening frailty evaluation by a trained research assistant. As part of the evaluation, 4-meter gait speed was assessed (at normal pace with non-ambulatory patients recorded as having a speed of zero). Disease-specific prognostic scores were obtained retrospectively, including the International Prognostic Index (IPI) for DLBCL, the Follicular Lymphoma International Prognostic Index (FLIPI) for FL, and the International Prognostic Scoring System for Waldenstrom Macroglobulinemia (ISSWM). Univariate and multivariable Cox proportional hazard models were used to determine predictors of overall survival (OS; from date of screening geriatric assessment) including gait speed and disease-specific scores. Those with incomplete risk data excluded from disease-specific analyses. Hazard ratios and generalized R2 (higher the R2, stronger association with OS) were also calculated. Results: A total of 145 patients were included, 59 with DLBCL, 30 with FL, 56 with WM. Median age was 79 (IQR 77 to 82) and 42.1% were female. For the overall cohort, mean gait speed was 0.78 (±0.27). Risk score distribution and disease-specific gait speed are presented in the table. With a median follow-up of 20.9 months (IQR 10.2 to 34.5), median OS was 14.4 months for DLBCL, 17.2 months for FL and 32.0 months for WM. Disease-specific prognostic scores were not predictive of survival for DLBCL (p = 0.76) or FL (p = 0.22) but were for WM (p = 0.04). Overall, faster gait speed was significantly predictive of OS (HR 0.10, 95% CI 0.03 to 0.32, p < 0.0001) for all three lymphomas combined, which would mean an HR of 0.56 for an increase of 0.25 m/s of gait speed. In disease-specific analyses, faster gait speed was predictive of survival for DLBCL (HR 0.10, 95% CI 0.02 to 0.46, p = 0.003) and WM (HR 0.11, 95% CI 0.01 to 0.83, P = 0.03) but not for FL (P = 0.26). In DLBCL, gait speed explained significant variability in OS (R2 = 22.95%) compared with IPI score (R2 = 1.87%; p = 0.005) whereas it did not for WM compared with IPSSWM (R2 = 10.22% vs. 5.58%, p = 0.11) or FL compared with the FLIPI (R2= 12.21% vs. 8.10%, p = 0.35). Conclusion: Gait speed may help to further refine the prediction of outcomes in patients with aggressive lymphomas beyond standard prognostic scores but may have less of an effect for indolent lymphomas. These data suggest that gait speed should be incorporated into the standard assessment of patients with aggressive lymphomas. Table Disclosures Buckstein: Takeda: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Soiffer:Mana therapeutic: Consultancy; Kiadis: Other: supervisory board; Juno, kiadis: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Gilead, Mana therapeutic, Cugene, Jazz: Consultancy; Cugene: Consultancy; Jazz: Consultancy.

Background Many patients with myelodysplastic syndromes (MDS) receive red cell transfusions to relieve symptoms associated with anemia, with transfusions triggered by hemoglobin level. It is not known if patients' quality of life (QOL) improves after transfusion, nor if peri-transfusion QOL assessment (PTQA) can guide future transfusion decisions. Study design and methods We conducted a prospective pilot study of adults with MDS at three centers. Participants, who had to have hemoglobin ≥7.5, completed an MDS-specific measure of QOL (the Quality of Life in Myelodysplasia Scale, [QUALMS]) 1 day before and 7 days after red cell transfusion. A report was sent to each patient and provider before the next transfusion opportunity, indicating whether there were clinically significant changes in QOL. We assessed the proportion of patients experiencing changes in QOL, and with a follow-up questionnaire, whether they perceived their PTQA data were used for future transfusion decisions. Results From 2018 to 2020, 62 patients enrolled (mean age 73 years) and 37 completed both pre- and post-transfusion QOL assessments. Of these, 35% experienced a clinically significant increase in QUALMS score 7 days after transfusion; 46% no change; and 19% a decrease. Among those completing the follow-up questionnaire, 23% reported that PTQA results were discussed by their provider when considering repeat transfusion. Conclusions These data suggest PTQA is feasible for patients with MDS. Moreover, while helpful for some, for many others, red cell transfusion may not achieve its intended goal of improving QOL. PTQA offers a strategy to inform shared decision-making regarding red cell transfusion.

Key Points Public demographic reporting for acute leukemia trials is inadequate, and NH-White subjects are more likely to be enrolled.Larger racial-ethnic enrollment disparities were documented after federal reporting requirements, which may be from more data transparency., Visual Abstract, Data regarding racial and ethnic enrollment diversity for acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) clinical trials in the United States are limited, and little is known about the effect of federal reporting requirements instituted in the late 2000s. We examined demographic data reporting and enrollment diversity for ALL and AML trials in the United States from 2002 to 2017, as well as changes in reporting and diversity after reporting requirements were instituted. Of 223 AML trials and 97 ALL trials with results on ClinicalTrials.gov, 68 (30.5%) and 51 (52.6%) reported enrollment by both race and ethnicity. Among trials that reported race and ethnicity (AML, n = 6554; ALL, n = 4149), non-Hispanic (NH)-Black, NH-Native American, NH-Asian, and Hispanic patients had significantly lower enrollment compared with NH-White patients after adjusting for race-ethnic disease incidence (AML odds ratio, 0.68, 0.31, 0.75, and 0.83, respectively; ALL odds ratio, 0.74, 0.27, 0.67, and 0.64; all, P ≤ .01). The proportion of trials reporting race increased significantly after implementation of the reporting requirements (44.2% to 60.2%; P = .02), but race-ethnicity reporting did not (34.8% to 38.6%; P = .57). Reporting proportions according to number of patients enrolled increased significantly after the reporting requirements were instituted (race, 51.7% to 72.7%; race-ethnicity, 39.5% to 45.4%; both, P < .001), and relative enrollment of NH-Black and Hispanic patients decreased (AML odds ratio, 0.79 and 0.77; ALL odds ratio, 0.35 and 0.25; both P ≤ .01). These data suggest that demographic enrollment reporting for acute leukemia trials is suboptimal, changes in diversity after the reporting requirements may be due to additional enrollment disparities that were previously unreported, and enrollment diversification strategies specific to acute leukemia care delivery are needed.

We conducted a randomized controlled trial in older adults with hematologic malignancies to determine the impact of geriatrician consultation embedded in our oncology clinic alongside standard care. From February 2015 to May 2018, transplant-ineligible patients aged ≥75 years who presented for initial consultation for lymphoma, leukemia, or multiple myeloma at Dana-Farber Cancer Institute (Boston, MA, USA) were eligible. Pre-frail and frail patients, classified based on phenotypic and deficit-accumulation approaches, were randomized to receive either standard oncologic care with or without consultation with a geriatrician. The primary outcome was 1-year overall survival. Secondary outcomes included unplanned care utilization within 6 months of follow-up and documented end-of-life (EOL) goals-of-care discussions. Clinicians were surveyed as to their impressions of geriatric consultation. One hundred sixty patients were randomized to either geriatric consultation plus standard care (n=60) or standard care alone (n=100). The median age of the patients was 80.4 years (standard deviation = 4.2). Of those randomized to geriatric consultation, 48 (80%) completed at least one visit with a geriatrician. Consultation did not improve survival at 1 year compared to standard care (difference: 2.9%, 95% confidence interval: -9.5% to 15.2%, P=0.65), and did not significantly reduce the incidence of emergency department visits, hospital admissions, or days in hospital. Consultation did improve the odds of having EOL goals-of-care discussions (odds ratio = 3.12, 95% confidence interval: 1.03 to 9.41) and was valued by surveyed hematologic-oncology clinicians, with 62.9%-88.2% of them rating consultation as useful in the management of several geriatric domains.

7537 Background: The recently reported ZUMA-7 and TRANSFORM trials demonstrate superior event-free survival among patients with primary refractory or early relapsed DLBCL compared to salvage chemotherapy with ASCT. However, given a cost of >$370,000, it is not known whether second-line CAR-T is cost-effective compared to ASCT. Thus, we developed a state-transition microsimulation model to simulate clinical outcomes and costs associated with therapy for DLBCL patients in first relapse, using ZUMA-7 and TRANSFORM data. Methods: The model begins at initiation of second-line therapy comparing salvage chemotherapy with ASCT or CAR-T therapy. We examined a three-year time horizon, including crossover to the alternative strategy therapy in the third line, as well as subsequent lines of therapy, using open-source Amua 0.3.0 software. Base case analysis was performed using 1000 first-order Monte Carlo simulations and probabilistic sensitivity analysis (PSA) was performed with 1000 simulations to test model uncertainty. Conditional probabilities of survival and disease progression were extracted from Kaplan-Meier curves from pivotal clinical trials using the WebPlotDigitizer tool. Costs were estimated from public sources in US Dollars ($) and effects were estimated in quality-adjusted life years (QALY) using published utility values. Results: Median overall survival was 15 months (95% confidence interval [CI] 13-19 months) with ASCT and 21 months (95% CI 17-29 months) with CAR-T. The PSA demonstrated costs and effectiveness per patient of $243,581 and 1.06 QALYs with ASCT and $470,150 and 1.22 QALYs with CAR-T with an incremental cost-effectiveness ratio (ICER) of $1,383,320/QALY. Incremental net monetary benefit of CAR-T versus ASCT, based on a willingness-to-pay (WTP) threshold of $200,000/QALY, was -$193,812. The break-even price for CAR-T and all subsequent therapies, based on a one-way sensitivity analysis, was $170,489. Conclusions: The model demonstrated improved survival and QALYs for the second-line CAR-T therapy, but was not cost-effective, as the ICER exceeded $1,000,000/QALY, which is higher than most accepted WTP thresholds. A limitation of these early data is that they only assess outcomes over three years. To estimate the full effect of these therapies, we will extrapolate the Kaplan-Meier curves for additional analyses. Clinical outcomes of second-line CAR-T are promising, but prices would need to be considerably lower to enable equitable access and affordability.[Table: see text]

12018 Background: Patients with AML experience substantial decline in their quality of life (QOL) and mood during their hospitalization for intensive chemotherapy. Yet, few interventions have been developed to enhance patient-reported outcomes during treatment. Methods: We conducted a randomized trial of a psychological mobile app (DREAMLAND) for patients with a new diagnosis of AML receiving intensive chemotherapy at Massachusetts General Hospital and Dana-Farber Cancer Institute. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND was tailored to the AML trajectory and included four required modules focused on 1) supportive psychotherapy to help patients deal with the initial shock of diagnosis; 2) psychoeducation to manage illness expectations; 3) psychosocial skill-building to promote effective coping; and 4) self-care. The primary endpoint was feasibility defined as at least 60% of eligible patients enrolling, and 60% of those enrolled completing at least 60% of the required modules. We assessed patient QOL (Functional-Assessment-of-Cancer-Therapy-Leukemia), psychological distress (Hospital-Anxiety-and-Depression-Scale [HADS] and Patient-Health-Questionnaire-9 [PHQ-9]), symptom burden (Edmonton-Symptom-Assessment-Scale), and self-efficacy (Cancer Self-Efficacy Scale) at baseline and day +20 post chemotherapy. We used ANCOVA to assess the effect of DREAMLAND on outcomes. Results: We enrolled 66.7% (60/90) of eligible patients and 62.1% completed ≥ 75% of intervention modules. At day +20 after intensive chemotherapy, patients randomized to DREAMLAND reported improved QOL (132.06 vs. 110.72, P = 0.001), lower anxiety (3.54 vs. 5.64, P = 0.010) and depression (HADS: 4.76 vs. 6.29, P = 0.121; PHQ-9: 4.62 vs. 8.35, P < 0.001) symptoms, and improved symptom burden (24.89 vs. 40.60, P = 0.007) and self-efficacy (151.84 vs. 135.43, P = 0.004) compared to the usual care group. Conclusions: A psychological mobile app for patients newly diagnosed with AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QOL, mood, symptom burden, and self-efficacy. Clinical trial information: NCT03372291.

Background Traditional count-based measures of comorbidity are unlikely to capture the complexity of multiple chronic conditions (multimorbidity) in older adults with cancer. We aimed to define patterns of multimorbidity and their impact in older United States veterans with multiple myeloma (MM). Methods We measured 66 chronic conditions in 5076 veterans aged 65 years and older newly treated for MM in the national Veterans Affairs health-care system from 2004 to 2017. Latent class analysis was used to identify patterns of multimorbidity among these conditions. These patterns were then assessed for their association with overall survival, our primary outcome. Secondary outcomes included emergency department visits and hospitalizations. Results Five patterns of multimorbidity emerged from the latent class analysis, and survival varied across these patterns (log-rank 2-sided P Conclusions Our findings demonstrate the need to move beyond count-based measures of comorbidity and consider cancer in the context of multiple chronic conditions.

Background:Intermittent shortages of chemotherapeutics used to treat curable malignancies are a worldwide problem that increases patient mortality. Although multiple strategies have been proposed for managing these shortages (eg, prioritizing patients by age, scarce treatment efficacy per volume, alternative treatment efficacy difference), critical clinical dilemmas arise when selecting a management strategy and understanding its impact.Patients and Methods:We developed a model to compare the impact of different allocation strategies on overall survival during intermittent chemotherapy shortages and tested it using vincristine, which was recently scarce for 9 months in the United States. Demographic and treatment data were abstracted from 1,689 previously treated patients in our tertiary-care system; alternatives were abstracted from NCCN Clinical Practice Guidelines in Oncology for each disease and survival probabilities from the studies cited therein. Modeled survival was validated using SEER data. Nine-month shortages were modeled for all possible supply levels. Pairwise differences in 3-year survival and risk reductions were calculated for each strategy compared with standard practice (first-come, first-served) for each 50-mg supply increment, as were supply thresholds above which each strategy maintained survival similar to scenarios without shortages.Results:A strategy prioritizing by higher vincristine efficacy per volume and greater alternative treatment efficacy difference performed best, improving survival significantly (PConclusions:During modeled vincristine shortages, prioritizing patients by higher efficacy per volume and alternative treatment efficacy difference significantly improved survival over standard practice. This approach can help optimize allocation as intermittent chemotherapy shortages continue to arise.

Importance State crisis standards of care (CSC) guidelines in the US allocate scarce health care resources among patients. Anecdotal reports suggest that guidelines may disproportionately allocate resources away from patients with cancer, but no comprehensive evaluation has been performed. Objective To examine the implications of US state CSC guidelines for patients with cancer, including allocation methods, cancer-related categorical exclusions and deprioritizations, and provisions for blood products and palliative care. Design, Setting, and Participants This cross-sectional population-based analysis examined state-endorsed CSC guidelines published before May 20, 2020, that included health care resource allocation recommendations. Main Outcomes and Measures Guideline publication before or within 120 days after the first documented US case of coronavirus disease 2019 (COVID-19), inclusion of cancer-related categorical exclusions and/or deprioritizations, provisions for blood products and/or palliative care, and associations between these outcomes and state-based cancer demographics. Results Thirty-one states had health care resource allocation guidelines that met inclusion criteria, of which 17 had been published or updated since the first US case of COVID-19. States whose available hospital bed capacity was predicted to exceed 100% at 6 months (χ2 = 3.82;P = .05) or that had a National Cancer Institute–designated Comprehensive Cancer Center (CCC; χ2 = 6.21;P = .01) were more likely to have publicly available guidelines. The most frequent primary methods of prioritization were the Sequential Organ Failure Assessment score (27 states [87%]) and deprioritizing persons with worse long-term prognoses (22 states [71%]). Seventeen states’ (55%) allocation methods included cancer-related deprioritizations, and 8 states (26%) included cancer-related categorical exclusions. The presence of an in-state CCC was associated with lower likelihood of cancer-related categorical exclusions (multivariable odds ratio, 0.06 [95% CI, 0.004-0.87]). Guidelines with disability rights statements were associated with specific provisions to allocate blood products (multivariable odds ratio, 7.44 [95% CI, 1.28-43.24). Both the presence of an in-state CCC and having an oncologist and/or palliative care specialist on the state CSC task force were associated with the inclusion of palliative care provisions. Conclusions and Relevance Among states with CSC guidelines, most deprioritized some patients with cancer during resource allocation, and one-fourth categorically excluded them. The presence of an in-state CCC was associated with guideline availability, palliative care provisions, and lower odds of cancer-related exclusions. These data suggest that equitable state-level CSC considerations for patients with cancer benefit from the input of oncology stakeholders.

BACKGROUND: Brief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults with blood cancers; however, little is known about whether such assessments are already captured within oncologists’ “gestalt” assessments. METHODS: Gait speed was assessed in 782 patients ≥75 years with blood cancers at our institution, with results reported to providers after treatment decisions were made; 408 required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN-based categorizations of oncologists’ treatment intensity recommendations, including gait speed. RESULTS: Median survival by gait speed category was 10.8 months (0.8 m/s). Univariable hazard ratios for death increased for each lower category compared to ≥0.8 m/s (0.6–0.8 m/s: HR 1.76; 0.4–0.6 m/s: HR 2.30; 0.05) and did not add to a base model predicting recommended treatment intensity. CONCLUSION: In older adults with blood cancers presenting for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision-making may improve optimal treatment selection.

The anemia of MDS often results in decreased quality of life, which is invoked to justify red cell transfusions; however, there are sparse data regarding the minimum hemoglobin (Hb) at which it is safe to forgo transfusions for patients with no evidence of end-organ damage. This issue is even more important in the COVID-19 era, where decreases in blood donations have stressed the blood supply. In March 2018, using a modified Delphi method, we convened a panel of 13 expert MDS clinicians for three iterative rounds to discuss a minimum safe Hb for this population. While the panel was unable to reach the pre-set consensus of 75% for a specific Hb threshold, there was 100% consensus that it be no greater than 7.5 g/dL. Our data suggest that, given no end-organ effects of anemia, patients with MDS can safely forgo transfusions with a Hb of 7.5 g/dL or higher.

Background: Older adults with acute myeloid leukemia (AML) represent a vulnerable population in whom disease-based and clinical risk factors, patient goals, prognosis, and practitioner- and patient-perceived treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel that included specialists in myeloid leukemia, geriatric oncology, patient-reported outcomes and decision-making, frailty, epidemiology, and methodology, as well as patients. The McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline-development process, including performing systematic evidence reviews (up to 24 May 2019). The panel prioritized clinical questions and outcomes according to their importance to patients, as judged by the panel. The panel used the GRADE approach, including GRADE’s Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 6 critical questions in managing older adults with AML, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management, the intensity of therapy, the role and duration of postremission therapy, combination vs monotherapy for induction and beyond, duration of less-intensive therapy, and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Treatment is recommended over best supportive management. More-intensive therapy is recommended over less-intensive therapy when deemed tolerable. However, these recommendations are guided by the principle that throughout a patient’s disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment.

Chemotherapies approved for defined subgroups promise personalized oncologic care, but their off-label impact is unclear. Lenalidomide is approved for lower-risk, transfusion-dependent (TD) myelodysplastic syndromes (MDS) with del(5q), but frequently used in MDS outside this indication. We characterized lenalidomide use and outcomes among non-TD patients with MDS. Patients 65 or older diagnosed with MDS between 2007 and 2013 were identified using SEER; linked Medicare claims were evaluated for transfusions, lenalidomide use, and incident toxicities. TD was ≥2 transfusion episodes within an 8-week period; responses were transfusion independence (TI) and ≥50% transfusion reduction (minor response). We compared overall survival for non-TD patients receiving lenalidomide versus those not receiving lenalidomide, matched on disease and patient characteristics. We identified 676 patients who had received lenalidomide, including 275 (40.7%) TD and 401 (59.3%) non-TD; 18.5% (125/676) had zero claims for RBC transfusion prior to receiving lenalidomide. Incident toxicities among patients prescribed lenalidomide were similar in TD and non-TD groups, except incident thromboembolic events were higher among non-TD patients (10.8% vs. 6.0%, P = .04). Comparing 191 non-TD patients receiving lenalidomide within 6 months of MDS diagnosis to risk-matched MDS controls, lenalidomide was not associated with improved OS (P = .78). Among TD patients (n = 275), 31% achieved TI, and 30% achieved minor hematologic response, with a median time to TI of 4.1 weeks. In conclusion, we confirmed the benefit of lenalidomide among TD patients with MDS; however, many non-TD patients also received lenalidomide. These patients experienced accompanying toxicity without evidence of benefit in terms of transfusion needs or overall survival.

BACKGROUND Although cancer drug shortages are a persistent problem in oncology, little is known about the awareness and perspectives of the US population with respect to shortages. METHODS In 2016, we administered a 13-item cross-sectional survey to 420 respondents who were randomly selected from an online, probability-based sample demographically representative of the adult US population with respect to sex, age, race/ethnicity, education, geography, and income. Analyses applied poststratification sampling weights to draw national inferences. RESULTS Overall, 16% of respondents reported being aware of drug shortages. Those with a personal history of cancer were more likely to be aware (31% vs 14% [P = .03]). In the overall cohort, most reported wanting to be informed about a substitution due to shortage: 87% and 82% for major or minor differences in efficacy, and 87% and 83% for major or minor differences in side effects. Most also reported they would transfer care to avoid a substitution: 72% for major differences in efficacy, and 61% for major differences in side effects. Black respondents, the uninsured, the unemployed, those with lower income, and the less well-educated were all less likely to report that they would transfer care to avoid major differences in efficacy (all P < .05). CONCLUSION These data suggest that the US population is largely unaware of cancer drug shortages. Moreover, if being treated for cancer, most people would want to know about drug substitutions, even if it were to result in only minor differences in efficacy or side effects. With more significant differences, many would transfer care. Cancer 2018;124:2205-11. © 2018 American Cancer Society.