Functional Assessment Of Cancer Therapy-Leukemia Research Articles

Research Strategy for the Development of a Quality-of-Life Decision-Making Model for Older Patients With Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a deadly cancer, especially for patients over 60 years of age who face the dilemma of choosing the best treatment during a time of crisis. Current research in the older AML population is focused on survival without addressing quality of life (QOL). Survival and QOL data are essential for patients to decide which treatment best aligns with their goals, whether for survival or improved QOL. Research aims: The aims of this study are to: (1) Describe differences in QOL among newly diagnosed older AML patients receiving intensive chemotherapy compared with nonintensive chemotherapy (at baseline, and days 30, 60, 90, and 180 post treatment); (2) Identify the individual clinical disease characteristics and patient factors of newly diagnosed AML patients that predict QOL among those receiving two treatment intensities; and (3) Design a patient decision-making model that integrates the significant clinical disease and patient factor predictors of QOL for newly diagnosed older AML patients. Methods: An exploratory observational design will be used to address aims 1 and 2. Data will be collected from 200 patients ≥ 60 years of age with newly diagnosed AML. Subjects will complete the Functional Assessment of Cancer Therapy-Leukemia, Brief Fatigue Inventory, and Memorial Symptom Assessment Short Form within 7 days of beginning new treatment and at days 30, 60, 90 and 180. Clinical disease characteristics will be completed by the health-care team. A patient decision-making model will be developed to provide survival and quality-of-life data for intensive and nonintensive chemotherapy.

Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML

Patient-reported outcomes (PROs) can inform treatment selection and assess treatment value in acute myeloid leukemia (AML). We evaluated PROs from the ADMIRAL trial (NCT02421939) in patients with FLT3-mutated relapsed/refractory (R/R) AML. PRO instruments consisted of Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), Functional Assessment of Chronic Illness Therapy-Dyspnea Short Form (FACIT-Dys SF), EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and leukemia treatment-specific symptom questionnaires. Clinically significant effects on fatigue were observed with gilteritinib during the first two treatment cycles. Shorter survival was associated with clinically significant worsening of BFI, FACT-Leu, FACIT-Dys SF, and EQ-5D-5L measures. Transplantation and transfusion independence in gilteritinib-arm patients were also associated with maintenance or improvement in PROs. Health-related quality of life remained stable in the gilteritinib arm. Hospitalization had a small but significant effect on patient-reported fatigue. Gilteritinib was associated with a favorable effect on fatigue and other PROs in patients with FLT3-mutated R/R AML.

Relationship Between Longitudinal Coping Strategies and Outcomes in Patients With Acute Myeloid Leukemia.

Patients with acute myeloid leukemia (AML) face an abrupt life-threatening illness and experience immense physical and psychological symptoms. However, no data describe how patients with AML cope longitudinally with their illness or the relationship between longitudinal coping and outcomes. We conducted a secondary analysis of longitudinal data from 160 patients with high-risk AML enrolled in a supportive care intervention trial to describe coping strategies longitudinally across the illness course. We used the Brief COPE questionnaire, the Hospital Anxiety and Depression Scale, the Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version, and the Functional Assessment of Cancer Therapy-Leukemia to measure coping strategies, psychological distress, and quality of life (QoL) at baseline and at weeks 2, 4, 12, and 24 after diagnosis. Electronic health records were used to assess healthcare utilization and end-of-life (EoL) outcomes, and multivariate analyses were used to assess the relationship between coping and outcomes. Longitudinal utilization of approach-oriented coping strategies was significantly associated with less distress (anxiety: β, -0.18; P<.001; depression symptoms: β, -0.42; P<.001; PTSD symptoms: β, -0.60; P<.001) and better QoL (β, 2.00; P<.001). Longitudinal utilization of avoidant coping strategies was significantly associated with greater distress (anxiety: β, 0.64; depression symptoms: β, 0.54; PTSD symptoms: β, 2.13; P<.001 for all) and worse QoL (β, -4.27; P<.001). Although the use of approach-oriented and avoidant coping strategies was not significantly associated with hospitalization, chemotherapy administration, or hospice use in the last 30 days of life, approach-oriented coping was associated with lower odds of ICU admissions (odds ratio, 0.92; P=.049). Longitudinal use of approach-oriented coping strategies was associated with less psychological distress, better QoL, and a lower likelihood of ICU admission, suggesting a possible target for supportive oncology interventions. Coping strategies did not impact EoL outcomes, and further research is needed to elucidate which patient factors impact EoL decision-making.

Patient-driven research: Initial results from a prospective health–related quality of life study performed at the request of patients living with hairy cell leukemia

A diagnosis of leukemia can have a profound effect on patients’ health-related quality of life (HRQoL), however this has not been measured prospectively in patients with hairy cell leukemia (HCL). At the request of patients living with HCL who had identified this gap in knowledge about the disease, we conducted a longitudinal study of HRQoL among patients enrolled in the HCL Patient Data Registry (PDR). From September 1, 2018 to September 1, 2020, 165 patients were enrolled in the study and completed the baseline survey. The Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu) was used to measure patients’ HRQoL. Results show that newly diagnosed HCL patients reported the lowest HRQoL, followed by patients in relapse and those on “watch and wait.” Factors associated with higher (better) FACT-Leu total scores in the multivariable analysis included older age, higher social support, and greater physical activity. These same factors were associated with lower levels of fatigue. In rare diseases where it is difficult to perform large prospective studies, patient/researcher collaborations are critical for the identification of studies that are of importance to patients and their families in order to maximize the benefits of the research and improve the lives of patients living with HCL.

Chronic disease management practices and factors associated with health-related quality-of-life for persons with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy.

The main objective of this study was to explore health-related quality of life (HRQoL) profiles, chronic disease management practices and key factors associated with HRQoL in 540 patients with chronic myeloid leukemia in chronic phase (CML-CP) administered tyrosine kinase inhibitors (TKIs). Adult CML-CP patients treated with TKIs in Henan Cancer Hospital from March 2015 to October 2019 were assessed via questionnaires, including demographic characteristics, TKI medications, participation in CML disease management, and HRQoL, in a cross-sectional investigation. Respondents were anonymous. Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used to measure HRQoL. A multivariate linear regression model with stepwise entry was used to investigate variables independently associated with HRQoL domain and total scores. Totally, 540 respondents were included; 302 (55.93%) were male. Mean participant age was 42.90±13.00 years; 169 (31.3%), 178 (32.9%) and 193 (35.7%) individuals had a low, moderate or high disease management level, respectively. Except for insignificant event-free survival information, participants with higher disease management levels also had significantly higher rates of completing re-examination, drug withdrawal, cytogenetic response (CcyR) and/or major molecular response (MMR) (all P<0.01). Moreover, higher disease management level was accompanied by eight significantly higher HRQoL domains (all P<0.01). In multivariate linear regression analysis, variables significantly associated with a higher HRQoL included: (I) high disease management level (B=3.68, P=0.046); (II) transportation convenience (B=6.67, P<0.001); (III) family annual income >10,000 CNY (B=5.97, P<0.001); (IV) completed re-examination (B=4.58, P=0.036); (V) MMR (B=3.75, P=0.021) and CcyR (B=5.15, P=0.035). Female sex (B=-3.53, P=0.010), single status or divorce (B=-1.89 and -2.94, P=0.005 and 0.011), and low education level (B=-1.44, P=0.019) were significantly associated with lower HRQoL. Higher disease management level was significantly associated with higher elevated treatment efficacy and HRQoL in Chinese individuals with CML-CP administered TKIs. These data indicate the importance of chronic disease management on people's HRQoL and clinical outcome.

Protocol for a pilot randomized controlled trial of a mobile health exercise intervention for older patients with myeloid neoplasms (GO-EXCAP 2)

IntroductionWe have shown the Exercise for Cancer Patients (EXCAP©®) exercise program improved physical function and symptoms and reduced inflammatory markers in patients with cancer. However, adherence to exercise was lower in older adults compared to their younger counterparts. We then leveraged a mobile app to deliver EXCAP©® and adapted the intervention [Geriatric-Oncology (GO)-EXCAP] for older patients with myeloid neoplasms. In this pilot randomized trial, the primary goal is to determine effect sizes. We propose to assess the preliminary efficacy of GO-EXCAP compared to a behavioral placebo control on physical function, patient-reported outcomes (fatigue, mood, and quality of life), and inflammatory markers in 100 patients aged ≥60 years with myeloid neoplasms receiving outpatient chemotherapy. MethodsGO-EXCAP consists of the EXCAP©® exercise prescription (daily home-based progressive aerobic walking and resistance exercises with rated perceived exercise of 5–8), EXCAP©® kit (i.e., activity tracker, resistance bands, print manual, bag), a mobile app, and an in-person or virtual session with the exercise physiologist to deliver exercise prescription. The intervention will last for three cycles of chemotherapy (approximately 12 weeks). The primary outcome measure will be physical function (Short Physical Performance Battery). Secondary outcome measures include fatigue (Brief Fatigue Inventory), mood (Center for Epidemiologic Studies Depression Scale), and quality of life (Functional Assessment of Cancer Therapy-Leukemia). Exploratory outcome measures include inflammatory markers. DiscussionOlder adults with myeloid neoplasms receiving outpatient chemotherapy serve as an ideal model for studying an individually tailored mobile health exercise intervention in vulnerable older patients receiving cancer treatments to prevent physical function decline and improve symptoms.

Patient Reported Outcomes in Patients with Newly Diagnosed FLT3mut+ acute Myeloid Leukemia Ineligible for Intensive Induction Chemotherapy from Lacewing: A Randomized Phase 3 Trial of Gilteritinib and Azacitidine Versus Azacitidine Alone

Patient Reported Outcomes in Patients with Newly Diagnosed FLT3mut+ acute Myeloid Leukemia Ineligible for Intensive Induction Chemotherapy from Lacewing: A Randomized Phase 3 Trial of Gilteritinib and Azacitidine Versus Azacitidine Alone

The Associations between Coping Strategy Use and Patient-Reported Outcomes in Patients with Acute Myeloid Leukemia

Background: Patients with acute myeloid leukemia (AML) who receive intensive chemotherapy must cope with immense physical and psychological symptoms associated with a variety of patient-reported outcomes (PROs) such as quality of life (QOL). Although coping is critical to the management of an AML diagnosis and its treatment, data characterizing the use of coping strategies and its associations with PROs in the AML population are limited. Hence, we characterize coping strategy use among patients with AML and examine the associations between coping strategy use, psychological distress, and QOL.Methods: We used cross-sectional secondary data analyses to describe coping in 160 patients with newly diagnosed high-risk AML enrolled in a multi-site randomized supportive care trial. We used the Brief COPE, Hospital Anxiety and Depression Scale (HADS), PTSD Checklist-Civilian Version (PCL-C), and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) within 72 hours of patient initiation of chemotherapy, to measure coping strategies, psychological distress and QOL, respectively. We grouped coping strategies into two higher-order domains of coping based on prior literature: approach-oriented coping (i.e., use of emotional support, active coping, positive reframing, acceptance) or avoidant coping (i.e., self-blame, denial, behavioral disengagement). We used the median split method for the distribution of coping domains. We used multivariate regression models adjusting for age, gender and diagnosis type (newly diagnosed vs. relapsed/refractory AML) to assess the relationship between coping and PROs.Results: Participants (median age of 64.4 years) were mostly non-Hispanic White (86.3%), male (60.0%), and married (73.8%). Most (51.9%) reported high utilization of approach-oriented coping strategies (e.g., emotional support) whereas 38.8% reported high utilization of avoidant coping strategies (e.g., denial) (Figure 1). At the time of AML diagnosis, use of approach-oriented coping was associated with less psychological distress and better QOL (Table 1). Use of avoidant coping was associated with more psychological distress and worse QOL. Additionally, patients who used multiple approach-oriented coping strategies had less psychological distress and better QOL (Table 2). In contrast, patients who used multiple avoidant coping strategies had more psychological distress, and worse QOL.Conclusions: Our study illustrates that most patients with high-risk AML utilize both approach-oriented and avoidant coping strategies. Our results also reveal links between approach-oriented coping strategies, less psychological distress, and better QOL. These findings underscore the need for early integration of supportive oncology interventions that help patients to cultivate approach-oriented coping strategies. [Display omitted] DisclosuresBrunner: Novartis: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Acceleron: Consultancy; Agios: Consultancy; Keros Therapeutics: Consultancy; GSK: Research Funding; Aprea: Research Funding; AstraZeneca: Research Funding; Janssen: Research Funding. Fathi: AbbVie: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Blueprint: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Trillium: Consultancy, Honoraria; Kura: Consultancy, Honoraria; Foghorn: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Ipsen: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Research Funding; Servier: Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding. LeBlanc: Seattle Genetics: Consultancy, Other: Advisory board, Research Funding; Pfizer: Consultancy, Other: Advisory Board; AstraZeneca: Consultancy, Honoraria, Other: Advisory board, Research Funding; UpToDate: Patents & Royalties; American Cancer Society: Research Funding; Agios: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding, Speakers Bureau; Daiichi-Sankyo: Consultancy, Honoraria, Other: Advisory board; Flatiron: Consultancy, Other: Advisory board; Astellas: Consultancy, Honoraria, Other: Advisory board; AbbVie: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Otsuka: Consultancy, Honoraria, Other; Jazz Pharmaceuticals: Research Funding; Duke University: Research Funding; Helsinn: Consultancy, Research Funding; Heron: Consultancy, Honoraria, Other: advisory board; CareVive: Consultancy, Other, Research Funding; NINR/NIH: Research Funding; Amgen: Consultancy, Other: travel.

Patient-reported outcomes predict overall survival in older patients with acute myeloid leukemia

IntroductionPatient-reported outcomes (PROs) predict overall survival (OS) in many cancer types, but there is little evidence of their prognostic value in older patients with acute myeloid leukemia (AML). We examined whether the Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu) predicted OS beyond established prognostic factors among these patients. Materials and MethodsData were from AML2002 (n = 309), a randomized phase 2/3 study comparing decitabine plus talacotuzumab versus decitabine alone in older AML patients ineligible for intensive chemotherapy. We used ridge-penalized Cox proportional hazards models to estimate the association between baseline FACT-Leu scales and OS. We then conducted a bootstrap analysis to determine how often FACT-Leu scales appeared in forward- and backward- selected “final models” predicting OS relative to prognosticators from the AML Composite Model (AML-CM; e.g., chronic comorbidities, previous cancer, cytogenetic/molecular risk). ResultsIn ridge-penalized models, the FACT-Leu Physical Well-Being (PWB), Trial Outcomes Index (TOI), and Total scales predicted OS. Adjusting for AML-CM factors, an important increase (3 points) in PWB score was associated with a 14% reduction in the hazard of death. In the bootstrap analysis, the PWB scale appeared in 93% of backward- and 98% of forward selected models, while the TOI [57% (backward), 79% (forward)] and FACT-Leu Total [51% (backward), 78% (forward)] appeared less often in final models. Discussion and ConclusionsThese results indicate PROs' value for predicting outcomes among older AML patients and underscore the need to more systematically collect PRO data in routine care with these patients.ClinicalTrials.gov Registration: NCT02472145

AML-084: Feasibility Study Integrating Electronic Patient-Reported Outcomes (PROs) and Palliative Care for High-Risk Acute Myeloid Leukemia (AML) Patients

Context: Despite recent lower-intensity therapies that have improved outcomes for older AML patients, AML remains associated with poor prognosis as well as high symptom burden. While the benefits of early palliative care and electronic PROs have been well-described in oncology patients, neither have been well-studied in AML, and they have never been studied in combination. Objective: To evaluate the feasibility of a virtually mediated supportive care model utilizing both electronic PROs and palliative care for patients with AML being treated with lower-intensity therapy (NCT04885127). Design: This will be a prospective, single-arm, non-blinded trial with a year of enrollment and six months of follow-up. Setting: All patients will be enrolled at Stanford Comprehensive Cancer Center. Patients or Other Participants: We plan on enrolling 40 patients who are on first-line lower-intensity therapy for AML, defined as therapy that allows patients to receive care exclusively in the outpatient setting. Interventions: Patients who are enrolled will be referred to the subspecialty palliative care clinic for virtual consultation and monthly follow-up visits for 6 months. Patients will also be instructed on the use of Noona, a digital application that allows real-time, remote monitoring of PROs. Patients will be requested to fill out a Noona symptom questionnaire prior to each palliative care visit and will be prompted to maintain a weekly symptom diary, which will be available to both their primary leukemia and palliative care providers. They will also fill out health-related quality of life surveys, including Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu), Hospital Anxiety and Depression Scale (HADS), Patient Health Questionnaire-9 (PHQ-9), and Satisfaction with Decision-Making Scale, at baseline, three, and six months. Main Outcome Measures: The primary outcome to be measured at completion of the study will be the feasibility of palliative care referral, defined as completion of the initial virtual consultation and at least 50% of the six scheduled monthly follow-up visits. Secondary outcomes will include the proportion of patients who complete the digital symptom questionnaires and the proportion of patients who complete their health-related quality of life surveys. Scores obtained from surveys will be used to generate hypotheses for future work. Despite recent lower-intensity therapies that have improved outcomes for older AML patients, AML remains associated with poor prognosis as well as high symptom burden. While the benefits of early palliative care and electronic PROs have been well-described in oncology patients, neither have been well-studied in AML, and they have never been studied in combination. To evaluate the feasibility of a virtually mediated supportive care model utilizing both electronic PROs and palliative care for patients with AML being treated with lower-intensity therapy (NCT04885127). This will be a prospective, single-arm, non-blinded trial with a year of enrollment and six months of follow-up. All patients will be enrolled at Stanford Comprehensive Cancer Center. We plan on enrolling 40 patients who are on first-line lower-intensity therapy for AML, defined as therapy that allows patients to receive care exclusively in the outpatient setting. Patients who are enrolled will be referred to the subspecialty palliative care clinic for virtual consultation and monthly follow-up visits for 6 months. Patients will also be instructed on the use of Noona, a digital application that allows real-time, remote monitoring of PROs. Patients will be requested to fill out a Noona symptom questionnaire prior to each palliative care visit and will be prompted to maintain a weekly symptom diary, which will be available to both their primary leukemia and palliative care providers. They will also fill out health-related quality of life surveys, including Functional Assessment of Cancer Therapy – Leukemia (FACT-Leu), Hospital Anxiety and Depression Scale (HADS), Patient Health Questionnaire-9 (PHQ-9), and Satisfaction with Decision-Making Scale, at baseline, three, and six months. The primary outcome to be measured at completion of the study will be the feasibility of palliative care referral, defined as completion of the initial virtual consultation and at least 50% of the six scheduled monthly follow-up visits. Secondary outcomes will include the proportion of patients who complete the digital symptom questionnaires and the proportion of patients who complete their health-related quality of life surveys. Scores obtained from surveys will be used to generate hypotheses for future work.

Palliative care and coping in patients with acute myeloid leukemia: Mediation analysis of data from a randomized clinical trial.

It has been shown previously that integrated palliative care for patients with acute myeloid leukemia (AML) during intensive chemotherapy leads to improvements in quality of life (QOL) and mood. Coping has been shown to mediate palliative care interventions in advanced cancer; the mechanisms by which improvements occur among patients with AML remain unexplained. The authors conducted a secondary analysis of data from a multisite randomized trial of integrated palliative and oncology care (IPC; n = 86) versus usual care (n = 74) for hospitalized patients with AML undergoing intensive chemotherapy. IPC patients met with palliative care at least twice weekly during their initial and subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy-Leukemia, the Hospital Anxiety and Depression Scale, and the Brief Coping Orientation to Problems Experienced Inventory to assess QOL, mood, and coping at the baseline and at weeks 2, 4, 12, and 24. Linear regression models were used to assess the effect of IPC on coping. Causal mediation regression models were used to examine whether changes in coping mediated intervention effects on patient-reported outcomes at week 2. One hundred sixty eligible patients (68.1%) were enrolled. Those randomized to IPC reported improvements in approach-oriented coping (P < .01) and reductions in avoidant coping (P < .05). These changes in coping mediated the intervention effects on QOL (95% CI, 2.14-13.63), depression (95% CI, -2.05 to -0.27), and anxiety symptoms (95% CI, -1.25 to -0.04). Changes in approach-oriented and avoidant coping accounted for 78% of the total palliative care intervention effect on QOL, for 66% of the effect on depression, and for 35% of the effect on anxiety symptoms. Palliative care integrated during intensive chemotherapy for patients with AML facilitates coping strategy use. Improvement in coping skills accounts for a substantial proportion of the effect from a palliative care intervention on patient-reported outcomes.

Cross-Sectional Survey of Symptoms and Health-Related Quality of Life of Adults with De Novo Acute Myeloid Leukemia (AML) in Clinical Practice

Introduction: The care of adults with acute myeloid leukemia (AML) is complex, involving repeated courses of chemotherapy; many patients suffer from sequelae of cytopenias and treatment-related toxicities that impair their health-related quality of life (HRQoL). Because knowledge regarding symptom burden and HRQoL is largely derived from academic centers' experience, there are uncertainties regarding how this compares to the real-world experience.Methods: The Adelphi AML Disease-Specific Program (DSP), a real-world, cross-sectional survey, was conducted in the US between February-May 2015; 61 hematologist/oncologists completed patient record forms for the next 6-8 adult patients with primary (de novo) AML with whom they consulted. Physicians reported demographics, clinical background, and treatment history for each patient. Patients were invited to complete the Functional Assessment of Cancer Therapy Leukemia (FACT-Leu) and EuroQoL 5 Dimensions (EQ-5D) questionnaires, which assess patient HRQoL and functional health status, respectively. Patients were categorized as newly diagnosed (NEW: currently on 1st line AML treatment), relapsed/refractory (RR: currently on 2nd line or later AML treatment), or not currently receiving active AML treatment (NO). Analysis of variance was used for quantitative outcomes, while chi-square and Fisher's exact tests were used for categorical outcomes, to determine statistical differences between patient groups. Effect sizes were calculated using Cohen's d. Minimally important differences (MIDs), required to suggest clinical importance on FACT-Leu and EQ-5D, were also examined.Results: Physician-completed data on 415 patients (median age: 61 years, 55% male) were obtained (NEW: 82%; RR: 12%; NO: 6%). At the time of most recent consultation, 46% of patients were currently in full or part-time employment, 31% required some caregiver support and 27% were considered asymptomatic. Among those who experienced symptoms, fatigue (24%), bruising (10%), loss of appetite (10%), and nausea (9%) were most common.When comparing subgroups, 58% of NO patients and 66% of RR patients were still in full or part-time employment compared with 42% of NEW patients; however, RR and NO patients were more likely than NEW patients to require some degree of caregiver support (RR: 48%, NO: 50%, NEW: 27%). The current symptom most commonly reported was fatigue (23% NEW, 32% RR, and 15% NO).Seventy-five patients (median age: 60 years, 53% male) provided self-reported information (68% NEW, 23% RR, and 9% NO). Results from the FACT-Leu indicated that physical well-being (PWB), leukemia-related well-being (LRW), well-being as measured by the Trial Outcome Index (TOI), and FACT-Leu Total Score were significantly affected by stage of treatment (PWB: p<0.001, LRW: p=0.002, TOI: p=0.011; Total: p=0.035), with NO patients consistently scoring lowest in all domains. Large differences in mean domain scores, exceeding the MIDs, were observed across the patient subgroups for the FACT-Leu. Large effect sizes were seen between NEW and NO patients for PWB (d=1.27 standard deviation units), LRW (d=1.35), and the TOI (d=1.02). Between RR and NO patients, large effect sizes were seen for functional well-being (FWB: d=0.80), and LRW (d=0.95). Between NEW and RR patients, a large effect was seen for PWB (d=0.83) and a moderate effect for TOI (d=0.54). In general, differences between NEW and RR patients were small to moderate, suggesting HRQoL was similar for the two patient populations, and differences between the NEW and NO group were moderate to large.Results from the EQ5D did not show a significant difference in the utility score between NEW (M=0.74), RR (M=0.73) and NO (M=0.76) patients. The effect sizes for any differences in EQ5D utility score were also small, whereas the difference between NO and RR patients for the EQ5D Visual Analogue Scale was moderate (d=0.57).Conclusions: In this novel real-world analysis of AML patients, differences in symptomatology, level of caregiver involvement, and HRQoL were observed across NEW, RR, and NO patients. Regarding HRQoL, the disease-specific FACT-Leu appears more sensitive than the EQ-5D, indicating that NEW patients overall fare better than RR patients, who fare better than NO patients. These results suggest effective and tolerable treatments that delay progression of the disease are important to conserve patients' HRQoL. DisclosuresMamolo:Pfizer Inc: Employment, Equity Ownership. Cappelleri:Pfizer Inc: Employment, Equity Ownership. Hoang:Pfizer Inc: Employment, Equity Ownership. Kim:Pfizer: Employment, Equity Ownership. Hadfield:Adelphi Real World: Employment. Middleton:Adelphi Real World: Employment. Rider:Adelphi Real World: Employment. Walter:Aptevo Therapeutics: Research Funding; ADC Therapeutics: Research Funding.

Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: 12-Month Patient-Reported Outcomes from the BFORE Trial

Introduction: Since many patients with chronic phase chronic myeloid leukemia (CP CML) achieve long-term survival, health-related quality of life (HR-QOL) as assessed by PROs is an important consideration. Bosutinib is a SRC/ABL tyrosine kinase inhibitor approved for Philadelphia chromosome-positive CML treatment in adults resistant or intolerant to prior therapy. In the BFORE trial (NCT02130557) of bosutinib versus imatinib a significantly higher major molecular response rate at 12 months (the primary endpoint) occurred with bosutinib. Here we report initial PRO results from BFORE.Methods: BFORE is an ongoing, multinational, phase 3, open-label study in patients with newly diagnosed CP CML. Patients are randomized 1:1 to bosutinib 400 mg once daily or imatinib 400 mg once daily. PROs, assessed as exploratory endpoints, included functional status using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and the European Quality of Life-5 Dimensions-Visual Analog Scale (EQ-5D-VAS) instruments. Assessments were conducted at baseline and every 3 to 6 months, to continue for up to 5 years after treatment initiation. Outcomes at month 12 are reported herein.Results: Bosutinib and imatinib mean FACT-Leu scores were similar at baseline and at month 12 (Table). At month 12, significant improvement from baseline in FACT-Leu total score was observed for both bosutinib (mean change 3.1, P=0.0425) and imatinib (mean change 4.8, P=0.0008). For bosutinib at month 12, all FACT-Leu combined and subscale scores demonstrated either improvement (emotional well-being; leukemia symptoms; FACT-Leu total score) or maintenance (physical, functional, social well-being; FACT-General total score; trial outcome index).Bosutinib and imatinib mean EQ-5D-VAS scores were similar at baseline and at month 12 (Table). At month 12, significant improvement in mean EQ-5D-VAS was observed for both bosutinib (mean change 4.4, P=0.0014) and imatinib (mean change 9.3; P <0.0001). Additional FACT-Leu and EQ-5D analyses yielded similar findings. For example, mean [SD] Functional Health Status as measured using the EQ-5D Utility Score was similar between groups at baseline (bosutinib: 0.688 [0.2710] and imatinib: 0.657 [0.2929]) and improved from baseline for subjects in both treatment arms, with comparable scores seen at Month 12 (bosutinib: 0.722 [0.2953] and imatinib: 0.724 [0.2717]).Conclusion: In the BFORE trial of first-line CP CML therapy, PROs for bosutinib indicated improvement or maintenance of HRQoL at month 12, with effects comparable to those observed for imatinib, the standard of care for first-line CML treatment. These exploratory PRO results indicate fewer symptoms, better HRQoL, and improved functional health status at month 12 relative to baseline for both therapies. [Display omitted] DisclosuresCortes:ARIAD: Consultancy, Research Funding; Sun Pharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Teva: Research Funding. Gambacorti-Passerini:Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Deininger:Novartis: Consultancy, Research Funding; Incyte: Consultancy; ARIAD: Consultancy; Ariad Pharmaceuticals, Bristol Myers Squibb, CTI BioPharma Corp, Gilead, Incyte, Novartis, Pfizer, Celgene, Blue Print, Galena: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; BMS: Consultancy, Research Funding; Celgene: Research Funding; Gilead: Research Funding. Mauro:Bristol-Myers Squibb: Consultancy. Chuah:Chiltern: Honoraria; BMS: Honoraria, Other: Travel; Novartis: Honoraria; Avillion: Honoraria. Kim:Il-Yang: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Milojkovic:ARIAD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria. le Coutre:Incyte: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Novartis: Honoraria, Research Funding; ARIAD: Honoraria. García Gutiérrez:BMS: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Reilly:Avillion LLP: Employment. Jeynes-Ellis:Avillion LLP: Employment, Equity Ownership. Crescenzo:Pfizer: Employment, Equity Ownership. Mamolo:Pfizer: Employment, Equity Ownership. Reisman:Pfizer: Employment. Bardy-Bouxin:Pfizer: Employment, Equity Ownership. Hochhaus:Novartis: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Ariad: Research Funding; MSD: Research Funding; BMS: Research Funding. Brümmendorf:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

Comparison of the anxiety, depression and their relationship to quality of life among adult acute leukemia patients and their family caregivers: a cross-sectional study in China.

To compare the anxiety, depression and explore their relationship to quality of life (QoL) among adult acute leukemia (AL) patients and family caregivers (FCs) in China. A multicenter cross-sectional study was conducted from April 2017 to January 2018. The sample comprised 207 dyads of adult AL patients and FCs. The participants were required to complete socio-demographic information and the Hospital Anxiety and Depression Scale (HADS). The Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu, only for patients) and MOS 36-item Short-Form Health Survey (SF-36, only for FCs) were used to measure QoL. The mean scores of anxiety and depression for AL patients were 7.89 ± 3.85 and 7.18 ± 4.23, respectively. For FCs, the mean scores of anxiety and depression were 9.96 ± 3.73 and 8.64 ± 3.74. In this study, adult AL Patients' sex, patients' depression score, whether patients achieving a CR or not, education, FCs' depression score, patients' social/family well-being and emotional well-being were significantly associated with patients' anxiety or depression (p < 0.05). For FCs, depression was significantly related to the physical component summary (β = 0.127, p = 0.008). There were significant differences in anxiety (t = - 5.92, p < 0.001) and depression (t = - 4.19, p < 0.001) between patients and FCs. AL patients' FCs showed higher score of anxiety and depression than that of patients. The psychological health may have a potential relationship between AL patients and their FCs. Healthcare professionals can conduct family-center interventions to improve mental health and QoL of AL patients and FCs.

Clinically Significant Fatigue in Adult Leukemia Patients: Prevalence, Predictors, and Impact on Quality of Life.

BackgroundCancer-related fatigue (CRF) is a common distressing symptom in leukemia patients. CRF becomes clinically significant fatigue (CSF) when adversely affects health-related quality of life (HRQoL) and warrants further workup, referrals, and treatment. Objective: To assess the prevalence and predictors of CSF and assesses its impact on HRQoL in adult leukemia patients.MethodAnalysis was performed on 168 leukemia patients. The primary study outcomes were CSF (score ≥4) as measured by the fatigue numerical rating scale and HRQoL using a validated Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) scale.ResultThe prevalence of CSF was 89 (53%), with a mean score of 6.66±2.02. About 106 (63.1%) of leukemia patients had poor Health-related quality of life (HRQoL) (102.61±23.50). Overall, FACT-Leu mean score indicated that study participants had poor HRQoL (114.70±29.67). There was a statistically significant difference in HRQoL between the patients with CSF 104.89±28.82 and Non-CSF 125.76±26.71, p<0.001. Poor appetite (odd ratio: 3.02 [95% CI: 1.33-6.85]) was statistically significant predictors (p<0.010) of CSF. Dependence on caregiver (odd ratio: 3.31 [95% CI: 0.41-0.75]) and having non-CSF (odd ratio: 5.22 [95% CI: 2.44-11.19]) were found statistically significant predictors of good HRQoL.ConclusionCSF is prevalent among leukemia patients, and adversely affects their HRQoL. Holistic assessment and supportive care are needed to reduce the burden of CSF and improve leukemia patients HRQoL.

Psychological Distress in Young Adults with Acute Myeloid Leukemia Undergoing Induction Chemotherapy

Introduction: Young adults (YAs), ages 18-39 years diagnosed with cancer have distinct physical, developmental, and psychosocial needs that are often unmet during oncologic treatment. In acute myeloid leukemia (AML), a disease affecting both younger and older adults, patients navigate several treatment intensity choices, and with intensive induction chemotherapy are often balancing a chance of cure with a risk of death. Furthermore, YAs with AML can have marked life disruptions with this unpredictable illness trajectory and prolonged induction hospitalization, further conflicting with normal development at this stage. Fundamentally different than solid tumors, we lack an understanding of the YA experience in AML induction compared to their older counterparts. This study explores patient-reported outcomes (PROs) including quality of life (QOL) and physical and psychological symptom burden among YAs undergoing induction chemotherapy. Methods: We conducted a secondary analysis of 160 patients with high-risk AML hospitalized to receive intensive chemotherapy who were enrolled in a randomized control trial of palliative care (PC) intervention versus standard oncology care. Patients with newly diagnosed, relapsed, or refractory AML receiving intensive treatment requiring a 4-6 week hospitalization were enrolled in the study. We used the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), the Edmonton Symptom Assessment System (ESAS), the Hospital Anxiety and Depression Scale (HADS), and the Post-Traumatic Stress Disorder (PTSD) Checklist to assess QOL, symptom burden, and psychological distress respectively. Assessments were administered at baseline, week-2, and week-4 following initiation of chemotherapy. We used descriptive statistics to compare PROs at baseline between YAs (&amp;lt; 40 years) and older adults. We used linear regression models controlling for PC intervention effect when examining the association between age (YAs versus older adults) and PROs at week-2. We used linear mixed effect models controlling for randomization to the PC intervention to assess the association between age and PROs longitudinally throughout the hospitalization. Results: Of the 160 patients with high-risk AML enrolled in this study, 14 (8.8%) were YAs &amp;lt; 40 years. Demographic characteristics highlight that the majority of YAs had relapsed AML (n=10, 71.4%) and there was a greater presence of racial and ethnic diversity compared to older adults. The baseline mean QOL score for YAs was 110.5 (SD 34.2). Overall, 57.1% (8/14) reported clinically significant anxiety and 50% (7/14) reported clinically significant PTSD symptoms at baseline. Fewer YA patients, 21.4% (3/14) reported clinically significant depression. Evaluation of PROs at week-2 nadir adjusted for randomization to the PC intervention, highlighted a significant lower QOL (β=-18.27; p=0.036), higher anxiety (β=2.72; p=0.048), and higher PTSD symptoms (β=10.34; p=0.007) for YAs compared to older adults. Longitudinal analyses exploring the impact of age on PROs across induction hospitalization demonstrated that YAs had consistently significant higher anxiety (β=3.66; p=0.024) and PTSD symptoms (β=15.64; p&amp;lt;0.001) compared to older adults [Figure 1]. Conclusions: For YAs with AML undergoing induction chemotherapy, anxiety and PTSD symptoms are highly prevalent both at baseline and longitudinally throughout the induction hospitalization. This demonstrates a continued unmet need of the significant psychological distress and intensified hospitalization experience for YAs compared to their older counterparts. Given that distress during induction hospitalization can be predictive of post-treatment outcomes, it is imperative to tailor integrated supportive care and psychosocial interventions for YAs with AML during induction chemotherapy. Disclosures Walker: Geron: Research Funding; Newave Pharmaceuticals: Research Funding. Bhatnagar:KaryoPharm Therapuetics: Research Funding; Cell Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees.

Multi-Site Randomized Trial of Integrated Palliative and Oncology Care for Patients with Acute Myeloid Leukemia (AML)

Background: Patients with AML receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). We sought to examine the effect of integrated palliative and oncology care on QOL, mood, post-traumatic stress (PTSD) symptoms, and EOL outcomes in patients with AML. Methods: We conducted a multi-center randomized trial of integrated palliative and oncology care (n=86) versus usual oncology care (n=74) for patients with AML undergoing intensive chemotherapy. Patients assigned to the intervention were seen by palliative care clinicians at least twice per week during their hospitalization for induction chemotherapy and all subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy-Leukemia, the Hospital Anxiety and Depression Scale, and the PTSD Checklist to assess their QOL, mood, and PTSD symptoms at baseline, weeks 2, 4, 12, and 24. The primary endpoint was QOL at week-2. We used analysis of covariance and mixed linear effect models, controlling for baseline scores, to assess the effect of the intervention on patient-reported outcomes. Results: Between 1/2017 and 7/2019, we enrolled 160/235 (68.1%) of eligible patients. Compared to those receiving usual care, intervention patients reported better QOL (107.59 vs. 116.45, P=0.039) and lower depression (7.20 vs. 5.68, P=0.021), anxiety (5.94 vs. 4.53, P=0.018), and PTSD symptoms (31.69 vs. 27.79, P=0.009) at week 2. Intervention effects were sustained up to week 24 for QOL (B=2.35, P=0.048), depression (B=-0.42, P=0.039), anxiety (B=-0.38, P=0.042), and PTSD symptoms (B=-1.43, P=0.002). Among deceased participants, those receiving the intervention were more likely to report discussing their EOL care preferences with their clinicians (75.0% vs. 40.0%, P=0.009) and less likely to receive chemotherapy in the last 30 days of life (34.9% vs. 65.9%, P=0.008). There was no difference in hospice utilization or hospitalization at the EOL. Conclusion: The integrated palliative and oncology care model for patients with AML receiving intensive chemotherapy led to substantial improvements in patients' QOL, psychological distress, and EOL care. Thus, palliative care should be considered a new standard of care for patients with AML. Disclosures Leblanc: UpToDate: Patents &amp; Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding. Luger:Acceleron: Honoraria; Agios: Honoraria; Loxo Oncology: Honoraria; Onconova: Research Funding; Kura: Research Funding; Hoffman La Roche: Research Funding; Ariad: Research Funding; Biosight: Research Funding; Daiichi-Sankyo: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria. Bhatnagar:Cell Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; KaryoPharm Therapuetics: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Fathi:TrovaGene: Consultancy; Forty Seven: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Blue Print Oncology: Consultancy; Boston Biomedical: Consultancy; Kura: Consultancy; Novartis: Consultancy; NewLink Genetics: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amphivena: Consultancy, Honoraria; AbbVie: Consultancy; Agios: Consultancy, Research Funding; PTC Therapeutics: Consultancy; Trillium: Consultancy; Takeda: Consultancy; Jazz: Consultancy, Honoraria; Daiichi Sankyo: Consultancy; Celgene: Consultancy, Research Funding; Astellas: Consultancy; Seattle Genetics: Consultancy, Research Funding. Hobbs:Novartis: Honoraria; Bayer: Research Funding; Incyte: Research Funding; Merck: Research Funding; Celgene/BMS: Honoraria; Constellation: Honoraria, Research Funding; Jazz: Honoraria.

Post-Traumatic Stress Disorder (PTSD) Symptoms in Patients with Acute Myeloid Leukemia (AML)

Background: Patients with acute myeloid leukemia (AML) receiving intensive chemotherapy face a life-threatening illness, experience a prolonged, isolating hospitalization, and endure substantial physical and psychological symptoms. Some patients with AML experience traumatic stress as a result of their diagnosis and illness course. As traumatic stress reactions can negatively impact patients' QOL, mood, and clinical outcomes, it is essential to understand the extent of this trauma, its clinical manifestations, and risk factors to inform targeted management strategies. Post-traumatic stress disorder (PTSD), characterized by experiencing a traumatic event, is a common stress related disorder in cancer populations. Despite the potential link between AML and PTSD, data are limited regarding risk and risk factors of PTSD symptoms in this population. Methods: We conducted a secondary analysis of 160 patients with high-risk AML hospitalized to receive intensive chemotherapy. We used the Post-Traumatic Stress Disorder Checklist-Civilian Version to assess PTSD symptoms at one month after diagnosis of AML. We used the Brief COPE, and Functional Assessment of Cancer Therapy-Leukemia at baseline and week-2 during hospitalization to assess coping and quality of life (QOL), respectively. We then used multivariate regression models to assess the relationship between PTSD symptoms at one month and patient baseline sociodemographic factors, coping, and QOL. Results: Twenty-eight percent of patients reported clinically significant PTSD symptoms, describing high rates of intrusion (92%), avoidance (100%), and hypervigilance (97%). Among those who did not have clinically significant PTSD symptoms, 27%, 26%, and 23% of patients reported clinically significant intrusion, avoidance, and hypervigilance symptoms, respectively. In adjusted analyses, higher baseline QOL (B= -.22, p= &amp;lt;.001) and less decline in QOL during hospitalization (B= -.17, p=.018) were associated with fewer PTSD symptoms. The use of approach-oriented coping (B= -.72; p= .018) was also associated with fewer PTSD symptoms, while the use of avoidant coping was not significantly associated with PTSD symptoms. Conclusion: A substantial proportion of patients with AML report clinically significant PTSD symptoms at one month after initiating intensive chemotherapy. These findings highlight the need to routinely screen, assess, and manage PTSD symptoms in all patients with AML. Patients' baseline QOL, coping strategies, and extent of QOL decline during hospitalization are important risk factors for PTSD symptoms, underscoring potential intervention targets in future studies to reduce the impact of PTSD in this population. Disclosures LeBlanc: Heron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Medtronic: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; American Cancer Society: Research Funding; BMS: Research Funding; Duke University: Research Funding; NINR/NIH: Research Funding; Jazz Pharmaceuticals: Research Funding; UpToDate: Patents &amp; Royalties; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; CareVive: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Flatiron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hobbs:Merck: Research Funding; Incyte: Research Funding; Celgene/BMS: Honoraria; Novartis: Honoraria; Jazz: Honoraria; Bayer: Research Funding; Constellation: Honoraria, Research Funding. Brunner:Novartis: Research Funding; AstraZeneca: Research Funding; Forty-Seven Inc: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Luger:Daiichi-Sankyo: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Acceleron: Honoraria; Agios: Honoraria; Loxo Oncology: Honoraria; Onconova: Research Funding; Kura: Research Funding; Hoffman La Roche: Research Funding; Ariad: Research Funding; Biosight: Research Funding. Bhatnagar:KITE: Membership on an entity's Board of Directors or advisory committees; KaryoPharm Therapuetics: Research Funding; Cell Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Targeted Literature Review of Patient Reported Outcomes (PROs) in Chronic Myeloid Leukemia (CML) Patients Receiving Second and Later Lines of Treatment

Background: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic CML in the last several years; however, the failure rates associated with TKIs still remain high in second line (50%) and later lines (75%-80%) treatment. Also, patients often experience adverse events associated with these TKIs, but are often left with no alternative treatment in real world practice which might result in TKI cycling. There is a need to understand the quality of life (QoL) and symptom burden among these patients, in order to better manage their disease and also to explore new treatments. The objectives of this study were to summarize the PROs among patients with CML receiving 2nd/3rd/4th line (2L/3L/4L) treatment, and the instruments used for QoL and symptom burden assessment in clinical trials and real world studies. Methods: Embase, MEDLINE, and the Cochrane Library were searched using pre-defined search terms to identify studies published from 1/1/2010 to 6/15/2020. Following the title/abstract and full-text screening based on the inclusion/exclusion criteria (see Table), one reviewer independently extracted all relevant data with random quality check (~20% of the sample) by a 2nd reviewer. Included studies reported QoL, symptom burden, or any PROs of adult CML patients who received 2L/3L/4L treatment. Only clinical trials and observational studies published in English were included, including conference abstracts. Results: Database search identified 1,377 records, which were screened to identify 20 studies (5 observational studies and 15 clinical trial-based studies) that met eligibility criteria (see Figure). Of the included studies, 16 targeted chronic phase CML patients only. More than half of the studies (n=14) focused on patients receiving 2L treatment (bosutinib, dasatinib, or nilotinib) only, and six reported QoL data on patients receiving 2L/3L/4L treatment, out of which four studies reported results by line of therapy. Out of 15 studies reporting a follow-up period, 13 observed patients ≥ 12 months with a maximum of 24 months. The duration between observations were usually 12 weeks for observational studies; while shorter duration was observed in clinical trials. Six clinical trial-based studies were associated with one trial (NCT00261846). Instruments used to assess QoL included four generic instruments [Functional Assessment of Cancer Therapy - General (FACT-G), EuroQol 5 dimension (EQ-5D), 36-Item Short Form Survey (SF-36), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)], three disease specific instruments [Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu), MD Anderson Symptom Inventory chronic myeloid leukemia (MDASI-CML), Comprehensive Symptom Profile in Chronic Myeloid Leukemia Patients (CSP Leuk-CML)], one Work Productivity and Activity Impairment (WPAI) questionnaire, and two additional general questions on QoL. Ten studies applied both generic and disease specific instruments altogether to evaluate patients' QoL and symptom burden. For 2L TKI treatment, studies have shown improvement in QoL following treatment; however, one study indicated that although patients were content with their QoL, they reported poor symptom scores on mobility, usual activities, and pain/discomfort. Among four studies examining PROs by line of therapy, only one study reported results on the 4L cohort individually, which showed lowest baseline FACT-G and FACT-Leu score in the 4L cohort compared to other cohorts, especially in terms of the physical and emotional well-being domain. Discrepancies existed in QoL between 2L- and 3L cohorts. Two studies found QoL to be similar between the 2L- and 3L cohorts, while the other two observed the QoL was lower in the 3L cohorts. In addition, three reported that QoL scores remained stable throughout observation period regardless of the line of therapy, but one study demonstrated the utility score got improved in the 2L but not the 3L cohort. Conclusions: Evidence on PROs in CML patients receiving 3L/4L treatment is very limited, especially real-world data. Existing research indicates patients with CML receiving later lines of treatment may have poor quality of life. Robust real-world studies with longer follow-up period are needed to provide evidence on later lines treatment management among CML patients. Disclosures Zhang: Novartis Pharmaceutical Corporation: Current Employment. Maegawa:Novartis Pharmaceutical Corporation: Current Employment, Current equity holder in publicly-traded company. Patwardhan:Novartis Pharmaceutical Corporation: Current Employment, Current equity holder in publicly-traded company.

Validated Instruments of Quality of Life (QOL) in Patients With Acute Myeloid Leukemia (AML) and Other Cancers.

IntroductionAcute myeloid leukemia (AML) can negatively impact quality of life (QOL). Few QOL instruments are specific to and have been validated in AML. This review aims to identify QOL instruments that have been validated in patients with AML and other cancers and summarize their psychometric properties reported in published literature. A literature review search was performed using PubMed and OVID (Biosis, Embase, MEDLINE) databases through June 25, 2020. Search terms included: QOL, health-related QOL, patient-reported outcomes and validity, reliability, validated, tools, instruments, test-retest, and leukemia myeloid acute, leukemia, myeloid, acute, acute myeloid leukemia. Articles were included if they focused on cancer and reported psychometric properties that could be extracted. s and their references were reviewed for inclusion.ResultsTwelve evaluating ten instruments were included. Functional Assessment of Cancer Therapy Leukemia (FACT-Leu) showed internal consistency (IC) of α = 0.86 to >0.9, correlation with EQ-5D-3L of r > 0.50, correlation with European Organisation for Research and Treatment of Cancer (EORTC) QLQ-Leu of ρ = 0.29–0.63, test-retest reliability of κ = 0.861. FACT-F showed correlations with EORTC QLQ-C30 of r = 0.40–0.83. Hematological Malignancy Patient-Reported Outcome (HM-PRO) showed intraclass correlation coefficient (ICC) of 0.94–0.98. EORTC-8D and EQ-5D-3L showed ICC = 0.595, correlations with each other of ρ = 0.137–0.634 and with EORTC QLQ-C30 of r = 0.651–0.917. EORTC QLQ-C30 showed person separation reliability of 0.47 to 0.90 and patient-observer agreement of 0.85. Life Ingredient Profile (LIP) showed IC of α = 0.29–0.77 and test-retest reliability of κ = 0.42–1.0. QOL-E showed correlation with FACT-general of R = 0.71, internal validity of α = 0.7, and test-retest reliability of standardized Cronbach’s α = 0.7–0.92. EORTC QLQ-Leu showed IC of α = 0.6–0.79. The Acute Myeloid Leukemia–Quality of Life (AML-QOL) instrument showed IC of α = 0.72, correlations with EORTC QLQ-30 of magnitudes ρ = 0.59–0.72, and test-retest reliability of ICC = 0.52–0.91.ConclusionAlthough several QOL instruments have been validated, more research is needed to determine the most clinically useful instruments in patients with AML.