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Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (-8.9) and disease symptoms (-10.2), and by month 2 for fatigue (-7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748. ispartof: BLOOD ADVANCES vol:6 issue:4 pages:1309-1318 ispartof: location:United States status: published

PURPOSE Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma. PATIENTS AND METHODS In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup. RESULTS At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients. CONCLUSION Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.

Lisocabtagene maraleucel (liso-cel) has shown promising efficacy in clinical trials for patients with relapsed/refractory large B-cell lymphoma (LBCL). We present health-related quality of life (HRQOL) results from the TRANSFORM study, the first comparative analysis of liso-cel vs standard of care (SOC) as second-line therapy in this population. Adults with LBCL refractory or relapsed ≤12 months after first-line therapy and eligible for autologous stem cell transplantation were randomized 1:1 to the liso-cel or SOC arms (3 cycles of immunochemotherapy in which responders proceeded to high-dose chemotherapy and autologous stem cell transplantation). HRQOL was assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – 30 items and the Functional Assessment of Cancer Therapy-Lymphoma subscale. Patients with baseline and ≥1 postbaseline assessment were analyzed (liso-cel, n = 47; SOC, n = 43). The proportion of patients with meaningful improvement in global health status/quality of life (QOL) was higher, whereas deterioration was lower in the liso-cel arm vs SOC arm from day 126 to month 6. Mean change scores showed meaningful worsening in global health status/QOL at month 6, fatigue at day 29 and month 6, and pain at month 6 with SOC; mean scores for other domains were maintained or improved in both arms. Time to confirmed deterioration favored the liso-cel arm vs SOC arm in global health status/QOL (median: not reached vs 19.0 weeks, respectively; hazard ratio, 0.47; 95% confidence interval, 0.24-0.94). HRQOL was either improved or maintained from baseline in patients with relapsed/refractory LBCL in the liso-cel arm vs SOC arm as second-line treatment. This study is registered at clinicaltrials.gov as #NCT0357531.

The programmed death-1 (PD-1) inhibitor nivolumab prolongs disease-free survival in patients with muscle-invasive urothelial carcinoma (MIUC).To evaluate the effects of nivolumab on health-related quality of life (HRQoL) after radical resection in patients with MIUC.We used data from 709 patients in CheckMate 274 (NCT02632409; 282 with programmed death ligand 1 [PD-L1] expression ≥1%), an ongoing randomized, double-blind, placebo-controlled phase 3 trial of adjuvant nivolumab.Intravenous injection of nivolumab (240 mg) or placebo every 2 wk for ≤1 yr.HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EQ-5D-3L. Linear mixed-effect models for repeated measures were used to compare nivolumab and placebo on changes in HRQoL. Time to confirmed deterioration (TTCD) of HRQoL was analyzed by Cox proportional hazards regression.In the full HRQoL evaluable population, no clinically meaningful deterioration of HRQoL was observed in either treatment arm. Moreover, nivolumab was noninferior to placebo on changes from baseline for all main outcomes. The median TTCD for fatigue was 41.0 wk for nivolumab and 44.3 wk for placebo (hazard ratio [HR]: 1.11, 95% confidence interval [CI], 0.89-1.39). For the visual analog scale, the median TTCD was not reached for nivolumab and it was 57.6 wk for placebo (HR: 0.78, 95% CI, 0.61-1.00). The median TTCD for the other main outcomes was not reached in either treatment arm. The findings were similar for patients with PD-L1 expression ≥1%.These results demonstrate that nivolumab did not compromise the HRQoL of patients with MIUC in CheckMate 274.Nivolumab is being researched as a new treatment for patients with bladder cancer (urothelial carcinoma). We found that nivolumab maintained quality of life while increasing the time until cancer returns in patients whose bladder cancer had spread or grown and who had unsuccessfully tried platinum-containing chemotherapy.

294 Background: TRANSCEND NHL 001 (TRANSCEND; NCT02631044) evaluated efficacy and safety of the CAR T cell therapy lisocabtagene maraleucel (liso-cel) as third-line or later treatment in patients with R/R LBCL. Prior research demonstrated improvements in HRQOL with liso-cel; however, evidence of HRQOL in the context of CAR T cell‒specific adverse events was not evaluated. In TRANSCEND, the incidence of all-grade cytokine release syndrome (CRS) and neurological events (NE) was 42% and 30%, respectively. This analysis examined longitudinal HRQOL in the presence of CRS and NEs among clinical responders. Methods: Patients in TRANSCEND who responded to liso-cel treatment (n = 137) were stratified into 3 groups: no CRS or NEs, either CRS or NEs but not both, and both CRS and NEs. HRQOL was evaluated with the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (QLQ-C30) and EQ-5D-5L. Summary statistics and change from baseline (liso-cel infusion; CFBL) were calculated for each time point. Results: For liso-cel‒treated patients who responded to treatment and developed CRS, NEs, or both, clinically relevant QLQ-C30 functional (physical, role, and cognitive) and fatigue scores indicated a noticeable nadir (low point) around 1 month post-baseline after liso-cel infusion, followed by a trend toward restoration of baseline status, generally achieved by 2 months after baseline. The primary difference between CRS/NE subgroups appeared to be the extent of decline or depth of the nadir. Patients with no CRS or NEs after liso-cel infusion did not experience an initial decrease in HRQOL/increase in symptom severity and instead showed a trend toward improvement over time (Table; QLQ-C30 fatigue as an illustrative example). This was also observed for EQ-5D-5L index scores. Conclusions: These findings support the anecdotal clinical experience that CRS/NEs are not associated with any long-term detriment in overall HRQOL and indicate a need for discussion with patients before treatment and early symptom monitoring and management of CRS or NEs. Clinical trial information: NCT02631044. [Table: see text]

OBJECTIVE: To understand the experience of patients with relapsed and refractory multiple myeloma (RRMM) receiving idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in the pivotal, phase 2 KarMMa trial. METHODS: Optional semi-structured interviews before leukapheresis (pre-treatment) captured expectations and after ide-cel infusion (1, 2, and 3 months post-treatment), assessed treatment experience, ide-cel advantages/disadvantages, and health and well-being. In a mixed-method analysis, treatment experiences were categorized by clinical response status, health and well-being, and self-reported recovery after infusion. RESULTS: Pre-treatment interviews indicated unmet treatment needs. In post-treatment interviews, most patients reported the positives of ide-cel outweighed negatives (69%, n = 27/39). Most common advantages of ide-cel were efficacy (18-64%), favorable side-effect profile (46-68%), and recovery time (13-18%); most common disadvantages were related to side effects (13-20%). When analyzed by clinical response, patients most often had stringent complete or very good partial response and improved health and well-being with mild or severe recovery from the infusion (27/58, 47%). Most patients with minimal clinical response reported mild infusion recovery (5/6, 83%). CONCLUSIONS: Patient interviews before ide-cel treatment showed unmet needs in triple-class exposed RRMM. Post-treatment experiences generally favored ide-cel versus previously received treatments. ispartof: LEUKEMIA RESEARCH vol:120 ispartof: location:England status: published

Background: Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy. Methods: HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model. Results: Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r>0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale. Conclusions: Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes. Trial registration: ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy.HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model.Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r 0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale.Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes.ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

6567 Background: PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed, CAR T cell product, as 2L tx in pts with R/R LBCL not intended for HSCT. We analyzed changes in health-related quality of life (QOL) with respect to functioning and symptoms in PILOT. Methods: Adults with R/R LBCL after first-line tx were eligible. Pts were deemed not candidates for high-dose chemotherapy and HSCT by their physician and met ≥ 1 frailty criteria: age ≥ 70 yr, ECOG PS = 2, DLCO ≤ 60%, LVEF < 50%, CrCl < 60 mL/min, or ALT/AST > 2 × ULN. Pts completed EORTC QLQ-C30, FACT-LymS, and EQ-5D-5L (health utility index [HUI] and VAS) at screening (baseline [BL]), pre-tx (within 7 days before lymphodepletion), preinfusion on day of liso-cel infusion (Day 1), post-tx on Days 29, 60, 90, 180, 270, 365, 545, and 730/end of study, or at PD. The PRO-evaluable set included all pts with BL and ≥ 1 post-BL assessments. Linear mixed-effects models for repeated measures assessed the least squares (LS) mean change from BL for visits with ≥ 10 pts. Meaningful change from BL was calculated using responder definitions (in points): 10 for EORTC QLQ-C30, 3 for FACT-LymS, 0.08 for EQ-5D-5L HUI, and 7 for EQ-VAS. Results: Among the PRO-evaluable set, completion rates were high (≥ 80%) across most visits for all measures. For EORTC QLQ-C30, mean BL fatigue was meaningfully worse than in a general noncancer population (difference of > 10 points). Overall LS mean changes through Day 545 showed significant improvements in EORTC QLQ-C30 fatigue and pain, FACT-LymS, and EQ-VAS (Table). Improvement for lymphoma symptoms was also clinically meaningful. Fatigue improvement was clinically meaningful with a more sensitive minimal important difference of 4 (Cocks et al, 2012). Significant worsening was not observed for any outcome. In individual patient-level analysis, 70% of pts demonstrated meaningful improvement in FACT-LymS at month 6. Conclusions: Liso-cel meaningfully improved fatigue and FACT-LymS scores without negatively impacting other QOL measures. These data support the clinical evidence of liso-cel as a potential new 2L tx in pts with R/R LBCL not intended for HSCT. Clinical trial information: NCT03483103. [Table: see text]

454 Background: Patient preference is an important factor in selecting appropriate treatment choices. Although underutilized, the standard of care for MIUC is with NAC, whereas evidence for adjuvant therapy is less clear. With the introduction of novel adjuvant treatments such as immune checkpoint inhibitors, treatment options are expected to expand. This study examines whether preferences for adjuvant therapy is impacted in MIUC patients receiving NAC. Methods: A cross-sectional, web-based survey included patients ≥ 18 years old who self-reported being diagnosed with MIUC and underwent radical cystectomy or nephroureterectomy without recurrence. Patients were recruited from the US, UK, Canada, France, and Germany (May–Sep 2021). A DCE using 2 adjuvant treatment profiles included 8 attributes: cancer-free survival, overall survival (OS), hypothyroidism requiring life-long hormone therapy, risk of a serious adverse event (requiring medical intervention/possible hospitalization), nausea, fatigue, diarrhea, and a dosing regimen (frequency of treatment and monitoring); an opt-out option of no treatment was also shown. Patients were grouped according to self-reported receipt of NAC. Descriptive statistics and hierarchical Bayesian logistic model with estimated preference weights were used. Relative importance estimates (mean ± standard error), or how much the attribute ranges accounted for the variation in preferences, were computed for each attribute. Bivariate comparisons used t-tests. Results: This interim analysis identified 205 patients (70.7% of target sample; US, n = 99; Germany, n = 60; UK, n = 31; Canada, n = 14; France, n = 1). Of 82 patients (40.0%) receiving NAC, 32.7% were patients > 65 years and 55.1% were male; receipt of NAC did not differ by age ( P = 0.248) or sex ( P = 0.731). Patients were willing to accept increased risk in toxicities for increased treatment efficacy. Specifically, mean relative importance of treatment attributes showed that difference in median OS (25 months compared to 78 months) was most important (34.6% ± 1.6), although less so for those who did not receive NAC (30.2% ± 2.4 vs 37.5% ± 2.0; P = 0.022). Patients chose an adjuvant treatment option over ‘no treatment’ 91% of the time, with similar findings by NAC status. Conclusions: Preliminary data indicates that receipt of NAC impacts preferences for adjuvant treatment attributes. However, regardless of these attributes, patients still preferred adjuvant treatment over none. These results suggest that providing standard of care NAC does not reduce patient preference for adjuvant therapy; rather, patient preferences for adjuvant treatment attributes vary by treatment history, with implications for improving quality of care and outcomes.

Pts with R/R LBCL had rapid and durable responses with liso-cel, a CD19-directed chimeric antigen receptor (CAR) T cell therapy. Previous qualitative research showed high perceptions of unmet pretreatment needs and largely positive pt experiences immediately after liso-cel infusion (Interviews 1-3; Siddiqi et al. Blood 2020;136 (suppl 1):22-23). We expanded our study to explore pt-perceived benefits and drawbacks after liso-cel treatment, up to 3 months. Pts in 2 ongoing phase 2 trials (TRANSCEND WORLD [NCT03484702] and PLATFORM [NCT03310619]) had the option to participate in a series of semi-structured guided interviews that included several closed-ended questions. Transcribed audio recordings were analyzed using the qualitative software package MAXQDA 2020. Inter-coder agreement exercises evaluated and ensured sufficient reliability. Analyses included thematic analysis, quantitative descriptive analysis of closed-ended items, and qualitative longitudinal analysis. The longitudinal analysis assessed changes in patients' physical functioning across three months following treatment. Change over time was conceptualized in terms of improvement, worsening, or stability. The direction of change was transformed into a categorical variable to enable a descriptive quantitative analysis. Closed-ended items assessed benefits and negative aspects of liso-cel treatment on a scale from 0 (no) to 10 (tremendous) and whether benefits outweighed negative aspects on a 5-point Likert scale ranging from "benefits greatly outweighed" to "negatives greatly outweighed." Results at Months 1 (Interview 4), 2 (Interview 5), and 3 (Interview 6) after CAR T cell infusion are presented. In total, 87 interviews (36, 29, and 22 interviews at Months 1, 2, and 3 after CAR T cell infusion, respectively) were analyzed across 40 pts in the United States and Europe, representing 34% of all participating pts by Month 3 (n = 118), or 50% of the 81 pts who received infusion by the same dates. Mean age of pts was 62.8 years; 70% were male. Most pts who described the infusion (27/29 [93%]) reported an overall positive impression, generally noting ease of, and time needed for, infusion. Common pt-reported side effects post infusion were fever (17/40 [43%]), weakness (13/40 [33%]), fatigue, and loss of appetite (8/40 [20% each]), which typically resolved during the first month. Overall, pts reported more benefits of liso-cel compared with other treatment options. Among pts who made comparisons between liso-cel and other available therapies (eg, chemotherapy, unspecified/other treatments, or stem cell transplantation), the percentage of pts reporting advantages were 90%, 100%, and 89%, respectively, whereas disadvantages were reported by 20%, 9%, and 11% of pts, respectively; 55% of pts who made comparisons to any prior treatment emphasized that liso-cel had a better side effect profile, others mentioned efficacy, infusion administration, or recovery time. At each time point, > 50% of respondents reported a benefits score within 8 and 10, and mean (standard deviation) scores across those who provided a numeric rating ranged from 8.42 (2.10) at Month 1 to 8.66 (1.38) at Month 3. The most common response across all interviews was 0/10 (no negative aspects). A small number (4/40 [10%]) considered the safety monitoring period after infusion a drawback compared with chemotherapy. Across 3 time points, 77%-88% of responders reported that the benefits of liso-cel outweighed any negative aspects (Table). Of pts asked if they would make the same decision to receive liso-cel therapy, knowing what they know now, and whether they would recommend the treatment to pts like them, 20/36 (56%), 20/29 (69%), and 17/22 (77%) answered "yes" at Months 1, 2, and 3, respectively. Three months after receiving treatment, 38% of patients were determined to have improved in terms of physical functioning since baseline, whereas 33% remained stable in this domain and 20% declined. This study provides insight into pt experiences with liso-cel from the first clinical trials of CAR T cell therapy with embedded pt interviews. It is yet unknown for some patients whether they were responsive to liso-cel, however most reported positive experiences, found it more tolerable than prior therapies, few considered postinfusion safety monitoring a drawback, and indicated they would still choose liso-cel if they had to make the decision again. Figure 1 Figure 1. Disclosures Siddiqi: Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Oncternal: Research Funding; Janssen: Speakers Bureau; TG Therapeutics: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jaeger: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Norvartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moshkovich: ICON plc: Current Employment. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Lanar: Roche: Consultancy; BMS: Consultancy; ICON plc: Current Employment. Miera: ICON Clinical Research: Current Employment. Salles: Novartis: Consultancy; Velosbio: Consultancy; Rapt: Consultancy; Regeneron: Consultancy, Honoraria; Takeda: Consultancy; Allogene: Consultancy; Morphosys: Consultancy, Honoraria; Miltneiy: Consultancy; Loxo: Consultancy; Kite/Gilead: Consultancy; Janssen: Consultancy; Ipsen: Consultancy; Incyte: Consultancy; Genmab: Consultancy; Genentech/Roche: Consultancy; Debiopharm: Consultancy; Epizyme: Consultancy, Honoraria; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria.

Introduction: Patients with heavily pretreated relapsed and refractory multiple myeloma (RRMM) have poor outcomes and poor health-related quality of life (HRQoL). The B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy ide-cel has shown frequent, deep, and durable responses in patients with RRMM who were triple-class exposed (TCE) to immunomodulatory drugs, proteasome inhibitors (PI), and anti-CD38 monoclonal antibodies in the pivotal, phase 2, single-arm KarMMa trial (Munshi NC, et al. N Engl J Med 2021;384:705-716). Ide-cel is approved in the US by the FDA for the treatment of adults with RRMM after ≥ 4 prior lines of therapy, including an immunomodulatory drug, PI, and anti-CD38 monoclonal antibody. We have shown previously that in the KarMMa trial, ide-cel provides clinically meaningful benefits in HRQoL at 9 months' follow-up (Delforge M, et al. HemaSphere 2020;4(suppl 1). Abstract EP1000; Shah N, et al. Blood 2020;136(suppl 1):28-29). The aim of this analysis was to extend previous reports by analyzing the effect of ide-cel on HRQoL at 24 months post-infusion data cut off (December 21, 2020) in patients with TCE RRMM in the KarMMa trial. Methods: In the KarMMa trial (NCT03361748), eligible patients had ≥ 3 prior antimyeloma treatment regimens, were TCE, and refractory to their last treatment regimen per International Myeloma Working Group criteria. To assess HRQoL, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 (QLQ-C30), EORTC QLQ Multiple Myeloma Module (QLQ-MY20) and EuroQoL 5 dimensions 5 levels (EQ-5D-5L) questionnaires were administered at screening, baseline, at ide-cel infusion, at months 1-6, and every 3-6 months up to month 24 or end of study. Thresholds for clinically meaningful changes from baseline were predefined. Statistical significance was calculated using the 2-sided Wilcoxon signed rank test (0.05 significance level). Results: Of 128 patients treated with ide-cel, 126 (98%) had a baseline and ≥ 1 post-baseline HRQoL assessment and were included in the HRQoL-evaluable population. The patient questionnaire completion rate was ≥ 75% up to month 6 and 50%-70% thereafter for most visits. For the predefined primary HRQoL domains, mean scores improved after ide-cel treatment and were comparable to the general population (Table). Mean changes from baseline exceeded the minimal important difference (MID) threshold for clinically meaningful improvement in fatigue, pain, physical functioning, cognitive functioning, and global health status/quality of life (QoL) scores of QLQ-C30 and disease symptom scores of QLQ-MY20 through month 24 (data cutoff, December 21, 2020). Side effects of treatment (QLQ-MY20) remained stable. Overall, 40%-70% of patients had clinically meaningful improvements in the QLQ-C30 fatigue, pain, physical functioning, and global health status/QoL scores at later timepoints. Moreover, 30%-40% of patients experienced clinically meaningful improvements in cognitive functioning, disease symptoms, and side effects, with 40%-60% of patients remaining stable in these domains, across most of the post-baseline assessment visits. Predefined secondary HRQoL domains included all other domains from QLQ-C30 and -MY20, EQ-5D-5L health utility index scores, and EQ-5D visual analogue scale (VAS) scores. Mean changes from baseline exceeded the MID thresholds for clinically meaningful improvement and reached statistical significance across most follow-up visits for role functioning, emotional functioning, social functioning, dyspnea, insomnia, constipation, diarrhea (QLQ-C30), future perspectives (QLQ-MY20), health utility index scores (EQ-5D-5L), and VAS scores (EQ-5D). Mean changes from baseline for nausea/vomiting, appetite loss, financial difficulties (QLQ-C30), and body image (QLQ-MY20) scores were not clinically meaningful. At the individual level, most patients remained stable or achieved clinically meaningful improvements in secondary domains of interest across almost all follow-up visits. Conclusion: In this study, patients with TCE RRMM who received a single infusion of ide-cel showed clinically meaningful improvements across multiple HRQoL domains during the 24-month follow-up period. Figure 1 Figure 1. Disclosures Delforge: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shah: Sanofi: Consultancy; Sutro Biopharma: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Kite: Consultancy; Indapta Therapeutics: Consultancy; Poseida: Research Funding; Nektar: Research Funding; Precision Biosciences: Research Funding; Karyopharm: Consultancy; GSK: Consultancy; CareDx: Consultancy; BMS/Celgene: Research Funding; Bluebird Bio: Research Funding; CSL Behring: Consultancy; Amgen: Consultancy; Teneobio: Research Funding. Rodríguez-Otero: Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy; Janssen, Celgene, Amgen, Oncopeptides, Sanofi, Abbvie, GlaxoSmithKline, Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Regeneron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda: BMS: Current Employment, Current equity holder in publicly-traded company. Shi: Bristol Myers Squibb: Consultancy. Guo: Bristol Myers Squibb: Consultancy; Daiichi Sankyo: Consultancy; UCB: Consultancy; Janssen: Consultancy; Gilead: Consultancy; EMD Serono: Consultancy; Evidera: Current Employment. Yu: Evidera: Current Employment. Liao: Evidera: Current Employment. Campbell: Bristol Myers Squibb: Current Employment, Current holder of individual stocks in a privately-held company. Munshi: Legend: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy.

Introduction: Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy, is approved by the US FDA for the treatment of adult patients (pts) with relapsed and refractory multiple myeloma (RRMM) after ≥ 4 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor (PI), and anti-CD38 antibody. In the pivotal, phase 2, single-arm KarMMa trial, ide-cel showed frequent, deep, and durable responses in pts with RRMM who were triple-class exposed to immunomodulatory drugs, PIs and anti-CD38 antibodies (Munshi NC, et al. NEJM 2021;384:705-716). To understand the pts' perspective on the advantages and disadvantages of ide-cel treatment that may not be captured by established health-related quality of life (HRQoL) questionnaires, a series of qualitative pt interviews were embedded into the KarMMa trial. This analysis focuses on time points between 6 and 24 months following treatment with ide-cel, providing an update on previously reported pt perspectives (Braverman J, et al. J Clin Oncol 2020;38(suppl 29). Abstract 155; Braverman J, et al. Value Health 2021;24(suppl 1). Abstract S61). Methods: Pts enrolled in the KarMMa trial (NCT03361748) were invited to participate in a series of optional interviews conducted at baseline and throughout the follow-up period. We present the results of qualitative interviews from months 6, 9, 12, 18, and 24 post treatment. Interviews were audio-recorded and transcribed. Non-English interviews were transcribed directly into English. Transcripts were analyzed using MAXQDA qualitative analysis software; inter-coder agreement exercises were used to ensure sufficient reliability. Analytic approaches included thematic analysis, quantitative descriptive analysis of close-ended items, and longitudinal analysis across HRQoL domains. Results: In total, 131 transcripts were analyzed for 45/128 unique pts treated with ide-cel in the US and Europe. The number of pts completing each interview steadily declined, from 36 at month 6 to 19 at month 24. The mean age of pts at the time of giving their consent in the trial was 63.5 years and 44% were female. Across time points, most pts (61%-79%) reported that positives of ide-cel outweighed negatives (Table). Overall, few pts reported that the negatives and positives were equal (n = 3), or that negatives outweighed positives (n = 5) across time points. The most frequent advantages were durability of treatment response (n = 23, 51%), improvements in HRQoL (n = 23, 51%), living a "normal life" (n = 19, 42%), and living for longer (n = 13, 29%). Additional frequent advantages were side effects after infusion, described as minor or not at all (n = 35, 78%), and ide-cel being a "one-time" treatment (n = 21, 47%). Common themes related to disadvantages were side effects after infusion (n = 27, 60%), the short response to treatment (n = 23, 51%), durability (n = 16, 36%), and lingering side effects (n = 18, 40%) that continued ≥ 3 months after infusion. Many pts also reported trial-related disadvantages (n = 31, 69%). At months 6, 9, 12, 18, and 24 post treatment, most pts (n = 33, 92%; n = 28, 88%; n = 18, 78%, n = 18, 86%; n = 18, 95%, respectively) reported they would make the same decision to receive ide-cel again, mostly due to positive results they had following treatment. Most pts (n = 29 [81%)], n = 27 [84%], n = 15 [65%], n = 17 [81%], and n = 16 [84%] at months 6, 9, 12, 18, and 24, respectively) reported they would recommend ide-cel treatment to others. The majority of pts (n = 26, 72%) described improvements in their physical health at 6 months post infusion versus baseline although this worsened for some at months 9-12 (n = 9, 25%) and 18-24 (n = 13, 48%) versus previous time points. Improvement in the emotional functioning domain was less common (n = 13, 36% at month 6 versus baseline, n = 5, 14% at months 9-12 and n = 4, 15% at months 18-24 versus previous time points) with most pts experiencing no change. Being optimistic was a common emotional concept expressed in interviews (n = 33, 73%). About half of pts (n = 21, 47%) experienced anxiety due to worry and fear of potential relapse. Conclusions: This study provides unique qualitative insights into the pt experience in the 24 months following ide-cel infusion. Overall, pts reported positive treatment experiences throughout interviews. Most pts reported they would make the same decision again to receive ide-cel and would recommend it to others. Figure 1 Figure 1. Disclosures Shah: Oncopeptides: Consultancy; Karyopharm: Consultancy; Poseida: Research Funding; Precision Biosciences: Research Funding; Sanofi: Consultancy; Sutro Biopharma: Research Funding; Kite: Consultancy; Janssen: Research Funding; Indapta Therapeutics: Consultancy; Bluebird Bio: Research Funding; BMS/Celgene: Research Funding; GSK: Consultancy; CSL Behring: Consultancy; CareDx: Consultancy; Nektar: Research Funding; Amgen: Consultancy; Teneobio: Research Funding. Delforge: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodríguez-Otero: BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen, Celgene, Amgen, Oncopeptides, Sanofi, Abbvie, GlaxoSmithKline, Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Regeneron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Moshkovich: ICON plc: Current Employment. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda: BMS: Current Employment, Current equity holder in publicly-traded company. Lanar: ICON plc: Current Employment; BMS: Consultancy; Roche: Consultancy. Miera: ICON Clinical Research: Current Employment. Gerould: ICON: Current Employment. Campbell: Bristol Myers Squibb: Current Employment, Current holder of individual stocks in a privately-held company. Munshi: Novartis: Consultancy; Abbvie: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Adaptive Biotechnology: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Pfizer: Consultancy; Legend: Consultancy.

Background: Pts with previously treated R/R aggressive LBCL have compromised health-related QOL (HRQOL). Liso-cel is an autologous, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. In a prespecified interim analysis of TRANSFORM (NCT03575351), a randomized, open-label, pivotal trial, liso-cel demonstrated statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival and key secondary endpoints (complete response rate and progression-free survival) in adults with R/R LBCL after failure of first-line (1L) immunochemotherapy compared with SOC, with no new safety signals. Here we present results of the pt-reported outcomes (PRO) analysis from TRANSFORM. Methods: Adults (age ≤ 75 yrs) with R/R LBCL (≤ 12 mo after 1L therapy), who were eligible for autologous stem cell transplantation (ASCT), were randomized to receive either SOC (3 cycles of salvage chemotherapy [CT] and BEAM + ASCT for responding pts) or liso-cel after lymphodepletion. Crossover to receive liso-cel was allowed in the SOC arm for pts who failed treatment. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) were administered at randomization (baseline) and on Days 29 (infusion of liso-cel or 2 cycles of salvage CT), 64 (1 mo post liso-cel or completion of CT), 126 (3 mos post liso-cel or 2 mos post ASCT), and Mo 6 and other prespecified timepoints up to Mo 36 or end of study. No PRO data were collected after crossover. The analysis was based on the PRO-evaluable population (pts with a baseline and ≥ 1 post-baseline assessment). Predefined thresholds determined clinically meaningful changes. Global health/QOL (GH/QOL), physical functioning, cognitive functioning, fatigue, pain, and FACT-LymS were the primary domains of interest based on their relevance to the study population and treatment. A linear mixed model for repeated measures (MMRM) analysis was performed to assess the between-treatment difference in overall least squares (LS) mean change from baseline for each primary domain, using data collected up to Day 126 for visits with a sample size per arm ≥ 10. Proportions of pts with meaningful change from baseline were assessed for each primary domain up to Mo 6. All analyses were descriptive only. Results: Of 184 randomized pts, 90 (49%) and 85 (46%), respectively, were included in the PRO-evaluable population for the EORTC QLQ-C30 (SOC vs liso-cel n=43 vs 47) and FACT-LymS (n=40 vs 45, respectively). The PRO assessment completion rate from baseline up to Mo 6 was ≥ 45%, which was lower than expected primarily due to operational challenges during the COVID-19 pandemic but was comparable for both arms. In the MMRM analysis, the liso-cel arm had more favorable overall LS mean changes from baseline to Day 126 than the SOC arm in most of the EORTC QLQ-C30 domains and FACT-LymS. In particular, the between-treatment differences for cognitive functioning (−2.09 vs 2.21) and fatigue (3.75 vs −1.95) for SOC versus liso-cel, respectively, exceeded the prespecified minimal important difference threshold (Table); in those domains, the SOC arm deteriorated while the liso-cel arm improved. In individual-level analyses, the proportion of pts with meaningful improvement for fatigue and GH/QOL was higher, while deterioration was lower, in the liso-cel arm versus SOC arm from baseline up to Mo 6 (Figure). At Mo 6, a higher proportion of pts experienced worsened fatigue (71% vs 18%) and a lower proportion experienced improved fatigue (29% vs 47%) in the SOC arm compared with the liso-cel arm; for GH/QOL, a higher proportion of pts worsened (57% vs 18%) and lower proportion improved (14% vs 53%), respectively. For the other primary domains, the proportions of pts with improvement or deterioration favored liso-cel or were similar between arms. Conclusions: Compared with SOC, liso-cel showed favorable improvement in most primary PRO domains, particularly EORTC QLQ-C30 cognitive functioning and fatigue and more pts showed PRO improvements and fewer showed deterioration by Mo 6 with liso-cel. The results were achieved despite only responders remaining in the SOC arm after salvage CT. HRQOL was either improved or maintained after liso-cel treatment in pts with R/R LBCL after failure of 1L therapy. Figure 1 Figure 1. Disclosures Abramson: Bristol-Myers Squibb Company: Consultancy, Research Funding; Morphosys: Consultancy; C4 Therapeutics: Consultancy; Kite Pharma: Consultancy; Kymera: Consultancy; Incyte Corporation: Consultancy; Bluebird Bio: Consultancy; Astra-Zeneca: Consultancy; Allogene Therapeutics: Consultancy; Novartis: Consultancy; EMD Serono: Consultancy; Genmab: Consultancy; Seagen Inc.: Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy; Genentech: Consultancy; BeiGene: Consultancy. Arnason: Juno/BMS: Honoraria. Glass: BMS: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Riemser: Research Funding; Kite: Consultancy; Novartis: Consultancy; Helios Klinik Berlin-Buch: Current Employment. Crotta: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Montheard: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Previtali: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Guo: Daiichi Sankyo: Consultancy; UCB: Consultancy; Janssen: Consultancy; Gilead: Consultancy; Bristol Myers Squibb: Consultancy; EMD Serono: Consultancy; Evidera: Current Employment. Shi: Bristol Myers Squibb: Consultancy. Kamdar: ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; TG Therapeutics: Research Funding; Genentech: Research Funding; AbbVie: Consultancy; KaryoPharm: Consultancy; Kite: Consultancy; AstraZeneca: Consultancy; SeaGen: Speakers Bureau; Celgene: Other; Genetech: Other; Celgene (BMS): Consultancy.

Background For pts with MM, HRQL is a key determinant of treatment choice in late-line therapies such as ide-cel, a BCMA-directed CAR T cell therapy. In KarMMa (NCT03361748), 54.2% of pts showed clinically meaningful improved HRQL from baseline to quarter (Q) 3, as measured by EQ-5D-5L; 8.5% experienced deterioration (Blood. 2020;136 [Suppl]:28–29). Analysis of HRQL in pts who received alternate, non-CAR T cell therapies could contextualize the impact of ide-cel on HRQL. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of largely community-based pts with newly diagnosed MM (NDMM) at study entry. It was used for a descriptive analysis assessing HRQL outcomes in triple-class exposed real-world pts who met KarMMa trial eligibility criteria but received alternate therapies. Method From 2009-2016, the Registry enrolled 3011 pts with symptomatic NDMM diagnosed ≤2 months prior to study entry at 250 community, academic, and government sites across the US. Pts agreed to complete HRQL forms at study enrollment and every Q of follow-up. Pts with RRMM included in this analysis met KarMMa eligibility criteria. HRQL was measured from the time of KarMMa eligibility (D1) using EQ-5D-3L and FACT-MM total score instruments. Results As of data cutoff (7 Feb 2020), 32 pts with RRMM from the Registry met KarMMa eligibility criteria. Median age was 64.1 y (range, 45.5–88.8). Median time to D1 since initial diagnosis was 3.4 y (range, 1.6–5.5); 24 pts (75%) had prior stem cell transplant; median prior lines of therapy was 7.5. At D1, pts initiated regimens that included IMiDs (n=20), proteasome inhibitors (n=15) and anti-CD38 monoclonal antibodies (n=7). HRQL form completion rate at Q3 was 64.7%. The baseline index score was 0.73 for Registry pts. Median EQ-5D-3L score (range) at D1 (n=21) was 0.761 (0.263–1) and 0.708 (0.263–1) at Q3 (n=11). At D1, 30% of pts experienced clinically meaningful improvement in EQ-5D-3L from baseline; 35% each experienced no change or deterioration in HRQL. By Q3, 20%, 30%, and 50% of pts experienced improvement from baseline, no change, and deterioration in HRQL, respectively. By Q3 post treatment initiation, a substantial proportion of ide-cel–eligible real-world pts with RRMM from the Connect MM Registry who received various alternate (non-CAR T cell) MM regimens experienced meaningful deterioration of HRQL (measured by EQ-5D-3L) from D1 over time. Conclusion In the context of the KarMMa trial, it was observed that a higher proportion of pts on ide-cel experienced meaningful improvement in HRQL (measured by EQ-5D-5L) and fewer pts experienced deterioration by Q3 after treatment. Limitations of this analysis may include small sample size and use of different versions of EQ-5D assessments. HRQL remains an important goal of MM treatment, and therapies that improve HRQL should be developed explicitly. These results support the need for replication in a larger pt sample and complement clinical trial findings.

Background : The main objectives of this study were to characterize and compare the burden of non-small cell lung cancer (NSCLC) patients reporting considerable unintentional weight loss (≥ 5% in the past 6 months or ≥ 2% for a BMI < 20 kg/m 2 ) to those who did not. Methods : Ninety-five advanced NSCLC patients were surveyed from the online patient-powered community PatientsLikeMe, which included health-related quality of life (QLQ-C15-PAL), anorexia-cachexia symptoms/concerns (FAACT A/CS domain), distress levels, clinical/demographic characteristics, and impact of weight loss (open-ended questions). Results : Thirty-five patients (37%) had considerable weight loss at the time of the survey and 60 (63%) did not. Mean age was 59 years, and most were female (81%) and American (81%). Patients with weight loss reported significantly (p < 0.05) lower overall quality of life (55.2 vs. 66.9), worsened anorexia-cachexia symptoms/concerns (30.7 vs. 36.0), and higher symptomology, specifically fatigue (64.8 vs. 49.1), nausea (19.5 vs. 9.2), and appetite loss (41.0 vs. 23.9) – than patients without weight loss. In addition, significantly more patients who lost weight reported moderate/high distress levels than patients who did not (71% vs. 38%). For patients with weight loss, changes in food taste, fatigue, and decrease in appetite were the most frequently reported symptoms with the greatest impact on their lives, and main worries included loss of energy and disease progression. Conclusions : Weight loss represents a substantial problem for NSCLC patients and symptoms associated with weight loss significantly impact patient lives. Interventions targeted at maintaining/increasing body weight may help to alleviate these findings.

Introduction: Patients with relapsed and refractory multiple myeloma (RRMM) have limited treatment options and experience poor health-related quality of life (HRQoL). Ide-cel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy, has shown a favorable clinical benefit-risk profile in patients with RRMM in the phase 2, single-arm KarMMa trial (Munshi NC, et al. J Clin Oncol 2020;38:8503). The impact of ide-cel treatment on primary HRQoL domains of interest preselected as most relevant for the treatment and target population (Fatigue, Pain, Cognitive Functioning, Physical Functioning, and Global Health) has been recently described (Delforge M, et al. HemaSphere 2020;4:EP1000). The aim of this analysis was to report the impact of ide-cel treatment on secondary HRQoL domains of interest and health utility scores in patients with RRMM in the KarMMa trial. Methods: Patients enrolled in the KarMMa trial (NCT03361748) had ≥ 3 prior antimyeloma treatment regimens (including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody) and were refractory to their last regimen per International Myeloma Working Group criteria. After lymphodepletion, patients received ide-cel at target dose levels of 150, 300 and 450 × 106 CAR+ T cells. HRQoL was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 (QLQ-C30) and Myeloma Module (MY20) questionnaires and the EuroQol 5 dimensions 5 levels (EQ-5D-5L) instrument at screening, baseline, on the day of ide-cel infusion, and throughout the follow-up period at Months 1-6, 9, 12, and 15 post-infusion. For each domain, clinically meaningful changes from baseline were predefined as recommended in the literature. Analyses were performed after the cutoff date, October 16, 2019, and included patients with ≥ 9+1 months of follow-up. Statistical significance was calculated using the 2-sided Wilcoxon signed-rank test (0.05 significance level). EQ-5D-5L utility indices were calculated using the UK value set as the reference country and compared with UK general population data. Results: Of 128/140 patients enrolled in the KarMMa trial who received ide-cel, 95% (EORTC QLQ-C30) and 94% (EORTC QLQ-MY20, EQ-5D-5L) had a baseline and ≥ 1 post-baseline HRQoL assessment and were evaluable for HRQoL. The compliance rate was ≥ 80% for most visits. For EORTC QLQ-C30, patients demonstrated a clinically meaningful improvement in most functioning and symptom subscale scores from baseline to Month 3 through 15, with statistical significance (p < 0.05) reached at various time points for different subscales throughout the follow-up period. For the Role Functioning, Emotional Functioning and Social Functioning subscales, > 40% of patients reported a clinically meaningful improvement from baseline, ~25% had deterioration and ~35% had no change from baseline from Month 2 onward (Figure shows Month 9 results). Stable status was most frequently observed (~60%) on the Nausea/Vomiting, Constipation, Diarrhea, Insomnia, Dyspnea and Appetite Loss, and Financial Difficulties subscales. For EORTC QLQ-MY20, the mean change from baseline on the Future Perspectives subscale demonstrated a clinically meaningful improvement from baseline at Month 2 through 15, with statistical significance (p < 0.05) reached at Month 5. Body Image subscale scores remained stable from baseline through Month 15. The greatest proportion of patients (> 48%) experienced a clinically meaningful improvement from baseline on the Future Perspective subscale. Stable status was most frequently observed (> 59%) for the Body Image subscale. Both EQ-5D-5L index (0.68 vs 0.86) and EQ visual analogue scale (EQ VAS) scores (68 vs 83) were lower for patients treated with ide-cel when compared with UK general population scores. The index and EQ-VAS mean scores became more comparable to the UK data over time, showing a clinically meaningful (although not statistically significant) improvement from baseline beginning at Month 2 (EQ-5D-5L) or 3 (EQ-VAS) through Month 15. In most patients, a clinically meaningful improvement from baseline was observed, increasing from ~43% to ~47% (EQ-5D-5L index score) and ~57% to ~68% (EQ-VAS). Conclusion: These results show that ide-cel treatment brings clinically meaningful quality-of-life benefits to triple-class-exposed patients with RRMM without compromising any HRQoL domains. Disclosures Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Delforge:Amgen: Honoraria; BMS: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bertin:ICON plc: Current Employment. Tahir:ICON plc: Current Employment. Lewis:ICON plc: Current Employment. Wang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Campbell:BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda:BMS: Current Employment, Current equity holder in publicly-traded company. Munshi:Takeda: Consultancy; C4: Current equity holder in private company; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy.

Introduction: Idecabtagene vicleucel (ide-cel, bb2121) is a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy under investigation in the KarMMa trial as a treatment for patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies. In the phase 2 KarMMa trial, ide-cel demonstrated a favorable benefit-risk profile in this patient population (Munshi NC, et al. J Clin Oncol 2020;38:8503). Ide-cel also demonstrated clinically meaningful improvements in the key health-related quality of life (HRQoL) symptoms associated with MM (Delforge M, et al. HemaSphere 2020;4:EP1000). Translating HRQoL data to health state utility values (HSUVs)/HRQoL weights is key to understanding the HRQoL impact of a treatment in relation to that of a healthy general population and is an important consideration in clinical decision making and health technology assessments. HSUVs are scored between 0 and 1, where 0 is death and 1 is perfect health. In the general population, individuals of a similar age range to patients with MM have HSUV scores of 0.83 in the USA, 0.80 in the UK, and 0.84 in Canada (Guertin JR, et al. CMAJ 2018;190:E155-161; Janssen MF, et al. Eur J Health Econ 2019;20:205-216). This analysis aimed to determine HSUVs for patients treated in the KarMMa study according to their progression status. Methods: HRQoL assessment in the KarMMa study (NCT03361748) included the European Quality of Life-5 dimensions 5 levels (EQ-5D-5L) health state classifier performed at specified time points: prior to receiving lymphodepleting chemotherapy (baseline), day of infusion (Day 1), Months 1, 2, 3, 6, 9, 12, and 15, inclusive of disease progression/relapse or complete remission. Using US, UK, and Canadian weights, HSUVs were estimated for the KarMMa trial at an aggregate level. A longitudinal mixed-effects model was used with health state as a fixed effect, and a random intercept term. Three models were run using different health states. Model 1 considered 3 health states: baseline, pre-progression, and post-progression. In Model 2, the pre-progression health state was split into 2 time periods: Day 1 to the end of Month 1, and Month 2 onward. In Model 3, 2 pre-progression health states were defined based on the quality of response to treatment, thus capturing the difference in HRQoL for patients achieving at least a very good partial response (≥ VGPR) or patients who did not achieve a VGPR (< VGPR). Results: The HSUVs derived from the 3 different models using US, UK, and Canadian tariffs are summarized (Table). In all 3 models, patients in the pre-progression state experienced an increase in HRQoL from baseline. In Model 1, the increment ranged from +0.05 to +0.08. On progression, patients experienced a decrement (−0.01 to −0.03), but their HSUV remained above the baseline value by +0.04 to +0.05, indicating that ide-cel treatment was associated with an improvement in HRQoL, with some of the benefit remaining even upon disease progression. When HSUV in the pre-progression state was analyzed in Model 2 at Month 1 and then Month 2 onward, patients also experienced an increase in their HRQoL from baseline. While this increase was small in Month 1 (+0.02 to +0.04), the subsequent increase from baseline (i.e. from Month 2 onward) was more pronounced (+0.07 to +0.10) reflecting the benefits of a one-off administration of ide-cel and the associated treatment-free interval. A further analysis of the pre-progression HSUV by the quality of response in Model 3 showed that patients who achieved ≥ VGPR had a greater improvement in HRQoL (+0.08 to +0.11) than patients who achieved < VGPR. Both response levels were associated with an improvement in HRQoL compared with baseline, with HRQoL for patients achieving ≥ VGPR approaching that of the general population (Figure). Conclusions: Results of this analysis indicate that ide-cel provides clinically meaningful improvements in HRQoL for patients with triple-class-exposed RRMM. The benefit is particularly marked in patients who achieve ≥ VGPR, in whom HRQoL approaches that of the general population. Disclosures Delforge: Janssen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Amgen: Honoraria. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Rodriguez-Otero:Celgene-BMS: Consultancy, Honoraria; Mundipharma: Research Funding; Janssen, BMS: Other: Travel, accommodations, expenses; BMS, Janssen, Amgen: Honoraria; Janssen, BMS, AbbVie, Sanofi, GSK, Oncopeptides, Kite, Amgen: Consultancy, Honoraria. Hari:Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; BMS: Consultancy; Incyte Corporation: Consultancy; Takeda: Consultancy. Braverman:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Trigg:Adelphi Values: Current Employment. Patel:BMS: Current Employment. Huang:BMS: Current Employment, Current equity holder in publicly-traded company. Hege:Arcus Biosciences: Divested equity in a private or publicly-traded company in the past 24 months; Mersana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; BMS: Current Employment, Current equity holder in publicly-traded company, Other: Travel, accommodations, expenses, Patents & Royalties: Numerous, Research Funding. Dhanasiri:BMS: Current Employment, Current equity holder in publicly-traded company.

In order to grasp the difference between “the cat on the mat” and “the mat on the cat,” understanding the words and the grammar is not enough. Rather it is essential to visually synthesize the cat and the mat together in front of the mind’s eye to appreciate their relations. This type of voluntary imagination, which involves juxtaposition of mental objects is conducted by the prefrontal cortex and is therefore called Prefrontal Synthesis (PFS). While PFS is essential for understanding of complex language, its acquisition has a strong experience-dependent critical period putting children with language delay in danger of never acquiring PFS and, consequently, not mastering complex language comprehension. In typical children, the timeline of PFS acquisition correlates with vocabulary expansion. Conversely, atypically developing children may learn hundreds of words but never acquire PFS. In these individuals, common tests of intelligence based on vocabulary assessment may miss the profound deficit in PFS. Accordingly, we developed a 5-minute test specific for PFS – Linguistic Evaluation of Prefrontal Synthesis or LEPS – and administered it to 50 neurotypical children, age 2 to 7 years (4.1±1.3) and to 23 individuals with impairments, age 8-21 years (16.4±3.0). All neurotypical children older than 4 years received the LEPS score 7/10 or greater indicating good PFS ability. Among individuals with impairments only 9 of 23 (39%) received the LEPS score 7/10 or greater. LEPS score was 90% correct in predicting high-functioning vs. low-functioning class assignment in individuals with autism, while full-scale IQ score was only 50% correct.

9574 Background: In CheckMate 238, NIVO 3 mg/kg vs ipilimumab 10 mg/kg showed significantly longer recurrence-free survival and a lower rate of grade 3–4 treatment-related adverse events (TRAEs) in pts with completely resected stage IIIB/C or IV melanoma. This analysis assessed the association of long-term HRQoL and TRAEs in NIVO-treated pts in this trial. Methods: HRQoL was assessed using EORTC QLQ-C30 (global health status [GHS] and physical/emotional functioning) and EQ-5D-3L visual analogue scale (VAS) questionnaires administered after randomization, during 1 y of treatment (wk 5, 7, 11, 17, 25, 37, and 49), at posttreatment FU visits 1 and 2 (FU1 and FU2; 30 and 114 days after last dose), and at survival FU visits up to 4 y after last dose (EQ-5D-3L only). NIVO-treated pts were grouped based on whether they had experienced a grade 3–4 TRAE, any-grade TRAE leading to NIVO discontinuation, or any-grade select (immune-related) TRAE on treatment or up to 100 days after last dose. Longitudinal change from baseline (BL) in scores was assessed for pts with and without TRAEs having patient-reported outcome data at BL and ≥1 post-BL assessment (HRQoL population) using descriptive statistics. QLQ-C30 subscale and VAS changes of 10 and 7, respectively, were considered clinically meaningful. Results: The HRQoL population comprised 446 of 453 pts randomized to NIVO. EQ-5D-3L assessments were completed by 81% of survivors (263/324) after 4 y post-randomization. Grade 3–4 TRAEs occurred in 17% of NIVO-treated pts (77/446). A slight trend toward deterioration of GHS from BL on treatment was noted, with clinically meaningful deterioration at posttreatment FU1 (mean [SD], −13.8 [25.0]) and FU2 (−10.3 [22.0]; last available time point). For the VAS, a similar trend on treatment was noted (−6.9 [28.3] at wk 11), with a clinically meaningful deterioration after NIVO discontinuation (−9.9 [27.0] at FU1) and a return to BL level by the start of survival FU. For pts without grade 3–4 TRAEs, mean change from BL scores remained stable (ie, no clinically meaningful deterioration on treatment or during FU). Any-grade TRAEs led to NIVO discontinuation in 9% of pts (42/446); HRQoL findings were similar to those for pts with grade 3–4 TRAEs. The most common any-grade TRAE was fatigue (35%). No clinically meaningful deterioration in VAS was noted for any select TRAE during FU except for hyperthyroidism (8%), with which deterioration occurred at FU1. EORTC QLQ-C30 physical and emotional functioning results will be presented. Conclusions: In CheckMate 238, pts with TRAEs showed early HRQoL deterioration after NIVO discontinuation, but HRQoL returned to BL levels with no sustained deterioration during survival FU. Overall, HRQoL was maintained on treatment and over a long-term FU period in pts with resected melanoma receiving adjuvant NIVO. Clinical trial information: NCT02388906.

4540 Background: Patients (pts) undergoing radical surgery for MIUC face a high risk of disease recurrence. Recurrence is associated with worse survival, but its effect on health-related quality of life (HRQoL) is unclear. This post hoc analysis assessed the impact of recurrence on HRQoL using data from the phase 3 CheckMate 274 trial. Methods: Pts who had undergone radical surgery for high-risk MIUC (≤ 120 days previously) were randomized 1:1 to nivolumab 240 mg Q2W or placebo for ≤ 1 year. HRQoL was assessed using the EORTC QLQ-C30 and EQ-5D-3L every 4–6 weeks during treatment; 35 and 115 days after the last dose; and every 3 months after that until the end of the study (EQ-5D-3L only). The analysis included pts with a valid HRQoL assessment at baseline and at ≥1 post-baseline visits. Confirmed deterioration in HRQoL was defined as worsening exceeding an a priori points threshold (± 10 for the EORTC QLQ-C30 domains, –7 for the EQ-5D visual analogue scale [VAS]) at ≥ 2 consecutive visits. Recurrence was classified as local only or distant (with or without local recurrence). The effect of recurrence on HRQoL deterioration was assessed by Cox proportional hazards regression with recurrence as a time-dependent covariate. The models controlled for treatment arm and baseline HRQoL score, and were stratified by PD-L1 expression, pathologic nodal status, and use of neoadjuvant cisplatin-based chemotherapy. Results: The analysis included 645 pts for EORTC QLQ-C30, of whom 71 (11%) had local recurrence only and 136 (21%) had distant recurrence during the HRQoL assessment period; and 648 pts for EQ-5D-3L. with recurrence had a significantly higher risk of confirmed deterioration in all HRQoL domains than those without recurrence (see table). However, hazard ratios were consistently greater for distant recurrence than for local recurrence across all HRQoL domains. For local recurrence only, a higher risk of confirmed deterioration in HRQoL compared to no recurrence was observed only for global health status/QoL. Conclusions: Recurrence, particularly distant recurrence, had a significant, negative impact on HRQoL. This suggests that treatment delaying recurrence after radical surgery for high-risk MIUC may prevent or delay HRQoL deterioration in these pts. Clinical trial information: NCT02632409. [Table: see text]

Ariella Kelman,1,2 Caroline O Robinson,1 Elisenda Cochin,3 Nina J Ahluwalia,1 Julia Braverman,3 Emil Chiauzzi,3 Kristina Simacek3 1Genentech, South San Francisco, CA, USA; 2Division of Immunology and Rheumatology, Stanford University Medical School, Stanford, CA, USA; 3PatientsLikeMe, Cambridge, MA, USA Objective: This study aimed to explore patient and physician perspectives on current laboratory test reporting practices and to elicit ideas for improvement. Methods: Two independent studies were conducted. The first solicited members of an online physician community for opinions on current laboratory test reporting practices and possible improvements. The second addressed the same topic, but solicited patient feedback, and included an evaluation of a mock laboratory test report for the rheumatoid factor blood test. Results: Both physicians and patients expressed a desire for patient-friendly information on laboratory reports. Physicians expressed a need for education for patients around false-positive and false-negative results within laboratory reports, while patients sought context around the meaning of results, relevance to other tests, and follow-up steps. Conclusion: Physicians and patients see value in enhancing laboratory test reports to improve communication. While reports should include the context that patients value, they should also contain cautionary interpretation emphasized by physicians. Patient consultation on improving laboratory reports may help improve such patient-focused communication and promote greater patient understanding of health information, thereby increasing patient participation in their own health care and improving outcomes. Practice implications: Laboratory reports are typically designed by experts. Including patients in laboratory report design may facilitate communication and improve outcomes through better patient engagement. Keywords: laboratory test reports, doctor–patient communication, patient-centered, medical records, health records

155 Background: Outcomes remain poor in triple-class exposed (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody) patients (pts) with relapsed and refractory multiple myeloma (RRMM), and there is no standard of care. Ide-cel, a BCMA-directed CAR T cell therapy, showed deep, durable responses in heavily pretreated RRMM pts in the pivotal phase 2 KarMMa trial ( J Clin Oncol 38:2020. Suppl; abstr 8503). Limited data are available on pts’ experience with prior therapies and expectations on ide-cel. By embedding pt interviews in KarMMa, we assessed pts’ initial knowledge of and expectations on ide-cel beyond pt-reported outcome measures prior to ide-cel therapy. Methods: This qualitative study was conducted in triple-class exposed pts refractory to their last regimen who entered the KarMMa trial (NCT03361748). Pts were invited to participate in the optional interview component that included up to 11 interviews. We present results of the first interviews that occurred between initial consent and leukapheresis. The interview topics were pts’ initial knowledge of ide-cel, decision making, expectations, hopes, and concerns, and current well-being. All interviews were recorded, transcribed, and coded. Results: Forty-seven pts from 14 clinical sites participated in the interviews. Most pts were able to describe the overall process of CAR T cell therapy and one third first heard about the therapy from their local healthcare professionals. According to patients, key decision-making factors were potential outcomes with ide-cel, recommendation from a doctor, and lack of other options. The most frequently perceived differences between ide-cel and prior treatments are shown (Table). Pt hopes were mostly focused on remission and improved quality of life. Most pts reported some restrictions on their daily activities due to the disease. Conclusions: RRMM pts need new treatment options. Most pts reported the limitations of prior therapies, expectations on ide-cel, impact of the disease, and differentiated ide-cel from other treatments. The ongoing interviews will further assess pt experience during and after ide-cel therapy. Clinical trial information: NCT03361748 . [Table: see text]

7533 Background: Effective AML maintenance treatment (Tx) should decrease the risk of relapse and prolong survival without compromising HRQoL. In the placebo (PBO)-controlled phase III QUAZAR AML-001 trial (NCT01757535), CC-486, an oral hypomethylating agent, provided significant improvements in overall (OS) and relapse-free survival (RFS) in patients (pts) with AML in first remission following IC. Here we present pt-reported HRQoL outcomes from that study. Methods: Eligible pts were ≥ 55 yrs of age with intermediate- or poor-risk cytogenetics and ECOG PS ≤ 3, and in CR/CRi after IC ± consolidation. Pts were randomized 1:1 to CC-486 300 mg or PBO QD on days (d) 1–14 of 28d Tx cycles. HRQoL was assessed by FACIT-Fatigue scale and EQ-5D-3L health utility index, completed on d1 of each cycle and at end of Tx (EOT). Endpoints include Tx differences in mean changes from baseline (BL), and proportions of pts with clinically meaningful change from BL (improvement, no change, deterioration). Evaluable pts had an HRQoL assessment at BL and ≥ 1 post-BL visit. Stratified ANCOVA models included Tx and BL scores as covariates. Results: In all, 225/238 pts (95%) in the CC-486 arm were evaluable for FACIT-Fatigue and EQ-5D-3L, and 219/234 pts (94%) in the PBO arm were evaluable for FACIT-Fatigue and 217 (93%) for EQ-5D-3L. Pt characteristics were comparable between Tx arms. Most pts (61%) were 65-74 yrs of age. Median number of CC-486 Tx cycles was 12 and PBO cycles was 7. Compliance rates were > 95% at BL and remained high ( > 85%) at all post-BL visits except for EOT. At BL, pts in both Tx arms had comparable low levels of fatigue and generally good HRQoL relative to an age-matched general population. There were no meaningful differences between CC-486 and PBO in mean changes from BL in FACIT-Fatigue or EQ-5D-3L scores at any post-BL visit. There was no statistically significant difference between Tx arms in proportion of pts with a clinically meaningful deterioration in FACIT-Fatigue score at any post-BL visit except at cycle 29 (likely due to chance; no adjustment made for multiple testing), or in EQ-5D-3L at any visit. Median time to deterioration was not significantly different between CC-486 and PBO on the FACIT-Fatigue scale (41 vs 44 weeks, respectively; P = 0.70) or the EQ-5D-3L (200 vs 164 weeks; P = 0.63). Conclusions: HRQoL and low levels of fatigue were preserved with CC-486 maintenance Tx. CC-486 significantly improved OS and RFS while maintaining HRQoL comparable to PBO. Clinical trial information: NCT01757535 .

Background: Although the quality of life (QoL) plays an important role in treatment decision making and clinical management of mycosis fungoides (MF) or Sezary syndrome (SS) subtypes of cutaneous T-cell lymphomas (MF/SS-CTCLs), an MF- or SS-specific measure of QoL does not exist. Objective: The objective of this research was to develop and validate the first QoL instrument for MF/SS-CTCL using a patient-centered approach. Methods: A conceptual framework for the MF/SS-CTCL QoL was developed through a literature review and interviews with key opinion leaders. Concept elicitation with patients was utilized to refine the conceptual model and generate preliminary items. The items were then revised based on qualitative and quantitative feedback obtained through cognitive debriefing surveys and interviews with patients. Next, participants (N=126) completed the preliminary MF/SS-CTCL QoL and a comparator measure of health-related QoL (Skindex-29) through the PatientsLikeMe Open Research Exchange. The MF/SS-CTCL QoL was completed again 5 days later by 66 participants for the purposes of evaluating test-retest reliability. The MF/SS-CTCL QoL was finalized based on results from an empirical evaluation, which included both classical and modern test theory approaches. Specifically, this included evaluation of (1) the optimal item response theory measurement model; (2) item fit; (3) unidimensionality; (4) rating scale performance; (5) reliability; (6) test information (precision); (7) person-to-item map; (8) convergent and discriminant validity; and (9) presence of bias via differential item function. Results: Results from the comprehensive psychometric evaluation utilizing a Rasch-Grouped Rating Scale model yielded a final 12-item instrument. The rating scale functioned as expected, and the instrument exhibited adequate person reliability (.87), good to excellent test-retest reliability (r=.89, P

BACKGROUND Although the quality of life (QoL) plays an important role in treatment decision making and clinical management of mycosis fungoides (MF) or Sézary syndrome (SS) subtypes of cutaneous T-cell lymphomas (MF/SS-CTCLs), an MF- or SS-specific measure of QoL does not exist. OBJECTIVE The objective of this research was to develop and validate the first QoL instrument for MF/SS-CTCL using a patient-centered approach. METHODS A conceptual framework for the MF/SS-CTCL QoL was developed through a literature review and interviews with key opinion leaders. Concept elicitation with patients was utilized to refine the conceptual model and generate preliminary items. The items were then revised based on qualitative and quantitative feedback obtained through cognitive debriefing surveys and interviews with patients. Next, participants (N=126) completed the preliminary MF/SS-CTCL QoL and a comparator measure of health-related QoL (Skindex-29) through the PatientsLikeMe Open Research Exchange. The MF/SS-CTCL QoL was completed again 5 days later by 66 participants for the purposes of evaluating test-retest reliability. The MF/SS-CTCL QoL was finalized based on results from an empirical evaluation, which included both classical and modern test theory approaches. Specifically, this included evaluation of (1) the optimal item response theory measurement model; (2) item fit; (3) unidimensionality; (4) rating scale performance; (5) reliability; (6) test information (precision); (7) person-to-item map; (8) convergent and discriminant validity; and (9) presence of bias via differential item function. RESULTS Results from the comprehensive psychometric evaluation utilizing a Rasch-Grouped Rating Scale model yielded a final 12-item instrument. The rating scale functioned as expected, and the instrument exhibited adequate person reliability (.87), good to excellent test-retest reliability (r=.89, P CONCLUSIONS Empirical evaluation demonstrated strong evidence of excellent psychometric properties. Utilizing a patient-centered measure development approach ensures that this QoL instrument captures the information that is most meaningful and clinically relevant to patients.

Background: Mental synthesis is the conscious purposeful process of synthesizing a novel mental image from objects stored in memory. In our everyday use of language, we rely on mental synthesis to communicate an infinite number of images with a finite number of words. In typical children, the timeline of mental synthesis acquisition is highly correlated with an increasing vocabulary. Children with ASD, on the other hand, may learn hundreds of words but never acquire mental synthesis. In these individuals, tests assessing vocabulary comprehension may fail to demonstrate the profound deficit in mental synthesis and the resulting inability to understand flexible syntax and spatial prepositions. Objective: We developed a 20-question parent-reported evaluation tool designed to quantitatively assess mental synthesis ability and to serve as a complimentary scale for Autism Treatment Evaluation Checklist (ATEC). Results: Internal reliability was good (Cronbach’s alpha > .9), and the MSEC exhibited adequate test-retest reliability after a three- and nine-months follow up period. The MSEC results positively correlated with the ATEC communication subscale, providing support for construct validity. Moreover, MSEC scores were significantly different for children of different ASD severity levels confirming the known groups validity. Conclusions: This study represents the first step toward the development of an instrument to measure mental synthesis in children with ASD. Although the current empirical evaluation demonstrated strong evidence of excellent psychometric properties, such as validity and reliability, additional studies should be performed to replicate these findings.

Most early-intervention Autism Spectrum Disorder (ASD) clinical trials are limited by the availability of psychometric technicians who assess each child’s abilities before and after therapeutic intervention. If parents could administer regular psychometric evaluations of their children, then the cost of clinical trials will be reduced, enabling longer clinical trials with the larger number of participants. The Autism Treatment Evaluation Checklist (ATEC) was designed nearly two decades ago to provide such a tool, but the norms on the longitudinal changes in ATEC in the “treatment as usual” population were lacking. Here we report the norms of the observational cohort who voluntarily completed ATEC evaluations over the period of four years from 2013 to 2017.

Introduction: The phase 3 international, randomized, double-blind ROBUST clinical trial (NCT02285062) compared progression-free survival between patients with previously untreated ABC-type DLBCL treated with placebo plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) versus lenalidomide + R-CHOP (R2-CHOP) for 6 21-day cycles. HRQoL, as measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EuroQoL 5-dimension 3-level (EQ-5D-3L) patient-reported questionnaires, was evaluated as a secondary endpoint for the 2 treatment arms. Methods: For each treatment group, FACT-Lym and EQ-5D-3L scores were measured at baseline (BL), mid-, end-of-treatment (EOT), and post-treatment, in 12-week intervals from Week 34 onward. Patients were evaluated if they had completed BL and ≥ 1 post-BL calculable FACT-Lym subscale measurements. Non-inferiority (NI) of R2-CHOP versus placebo-R-CHOP was measured for 4 key FACT-Lym subscales: Physical Well-Being (PWB), Additional Concerns (AC), Functional Well-Being (FWB), and Trial Outcome Index (TOI). NI was assessed at EOT (typically 3-4 weeks after completing Cycle 6) and at post-treatment follow-up at Week 34 by analysis of covariance (ANCOVA). The NI margins were prespecified as 1 less than the higher published minimal important difference (MID) for each subscale. Since a range of MIDs have been published, a more conservative value was also used as a sensitivity analysis. Time to improvement (TTI), using published responder definitions, was also assessed for the FACT-Lym subscales. EQ-5D-3L scores were summarized descriptively. Results: Demographic and baseline disease characteristics were balanced across the 2 treatment arms (N = 285 per arm). The percentage of patients who completed the FACT-Lym out of the expected population remained > 85% at all time points with > 50 patients still on the study in each treatment arm up to Week 142. Completion rates and reasons for missing assessments were balanced across the 2 treatment arms. FACT-Lym subscale scores were generally higher after EOT, similar for both treatment groups, and mean changes from BL were close to or above MID (where defined), except for the Social/Family Well-Being subscale. Mean differences in FACT-Lym TOI between treatment arms are shown in Table 1. As positive treatment differences favor R2-CHOP and -10 was the predefined NI margin, NI was demonstrated for the FACT-Lym TOI subscale at both EOT and Week 34 assessments. Superiority of R2-CHOP was demonstrated at EOT as the confidence interval (CI) lies completely above 0 (P < 0.04); however, this difference was not clinically meaningful. Furthermore, NI was also demonstrated when using the sensitivity analysis margin of -4.5. ANCOVA models were also fitted for the other key subscales of PWB, AC and FWB (Table 2). NI was demonstrated for all NI margins at both time points for the PWB and AC subscales. The FACT-Lym FWB subscale demonstrated NI for both margins at EOT and Week 34 for the primary NI margin of -2 based on the MID minus 1, but did not demonstrate NI when an NI margin of -1, based on an alternative published MID, was used. The TTI curves and associated summary statistics were similar for the 2 treatment arms, with a median TTI for the FACT-Lym TOI of 21 weeks (95% CI 15-22) for patients treated with R2-CHOP and 18 weeks (95% CI 15-22) for patients treated with placebo-R-CHOP. Mean EQ-5D-3L visual analogue scale (VAS) and Utility Index (UK weights) change from baseline scores were higher in both treatment arms and the mean changes were above, or close to, the published MID (7 for VAS, 0.1 for Utility Index) at EOT assessments. Prespecified sensitivity and subgroup analyses supported the conclusions from the primary HRQoL analyses. Conclusions: The predefined NI levels were met for the 4 key FACT-Lym subscales. Similar results were observed across the other HRQoL assessments, sensitivity, and subgroup analyses. Adding lenalidomide to the R-CHOP regimen did not adversely affect the HRQoL of patients with DLBCL as measured by FACT-Lym and EQ-5D-3L. These data serve as a benchmark for future clinical trials combining next-generation immunomodulatory drugs with standard R-CHOP to improve clinical efficacy while maintaining HRQoL in patients with DLBCL. HRQoL analyses should become an integral part of future clinical trials of novel combination regimens in DLBCL. Disclosures Chiappella: Roche: Speakers Bureau; Teva: Speakers Bureau; Servier: Other: advisory board, Speakers Bureau; Janssen: Other: advisory board, Speakers Bureau; Celgene: Other: advisory board, Speakers Bureau. Cocks:Adelphi Values: Employment; Amgen: Consultancy; BMS: Consultancy; Celgene Corporation: Consultancy; Endomag Ltd.: Consultancy. Greenwood:Adelphi Values: Employment. Williams:Adelphi Values: Employment. Scott:Celgene: Consultancy; Roche/Genentech: Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Janssen: Consultancy, Research Funding. Yamamoto:SymBio: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Otsuka: Honoraria; Sanofi: Honoraria; Astra-Zeneca: Consultancy, Research Funding; Sumitomo Dainippon: Honoraria; Chugai: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Gilead Sciences: Research Funding; Solasia Pharma: Research Funding; Bayer: Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; ARIAD: Research Funding; Pfizer: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Kyowa Kirin: Honoraria; MSD: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Research Funding; Meiji Seika Pharma: Consultancy, Honoraria; HUYA/IQVIA Services Japan: Consultancy, Honoraria; Novartis: Honoraria, Research Funding; Incyte: Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Jurczak:Bayer: Research Funding; Takeda: Research Funding; Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Incyte: Research Funding; Celgene Corporation: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celtrion: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding. Özcan:Sanofi: Other: Travel support; Abdi Ibrahim: Other: Travel support; BMS: Other: Travel support; Takeda: Honoraria, Other: Travel support, Research Funding; Archigen: Research Funding; Roche: Other: Travel support, Research Funding; Bayer: Research Funding; Janssen: Other: Travel support, Research Funding; Celgene Corporation: Research Funding, Travel support; AbbVie: Other: Travel support, Research Funding; MSD: Research Funding; Novartis: Research Funding; Jazz: Other: Travel support; Amgen: Honoraria, Other: Travel support. Belada:Roche: Consultancy; Gilead Sciences: Consultancy; Takeda: Consultancy. Margunato-Debay:Celgene Corporation: Employment, Equity Ownership. Czuczman:Celgene Corporation: Employment, Equity Ownership. Zhai:Celgene Corporation: Employment, Equity Ownership. Braverman:Celgene Corporation: Employment. Vitolo:Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche: Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

This study is the first to compare the accuracy of self-reported with actual monetary outcomes of online fixed odds sports betting, live action sports betting, and online casino gambling at the individual level of analysis. Subscribers to bwin.party digital entertainment's online gambling service volunteered to respond to the Brief Bio-Social Gambling Screen and questions about their estimated gambling results on specific games for the last 3 or 12 months. We compared the estimated results of each subscriber with his or her actual betting results data. On average, between 34% and 40% of the participants expressed a favorable distortion of their gambling outcomes (i.e., they underestimated losses or overestimated gains) depending on the time period and game. The size of the discrepancy between actual and self-reported results was consistently associated with the self-reported presence of gambling-related problems. However, the specific direction of the reported discrepancy (i.e., favorable vs. unfavorable bias) was not associated with gambling-related problems.

Plain English summary Plain English summary PLM is an online platform that provides tools for individuals to track their health and connect with other patients and while PLM has invited patients to participate in various research projects throughout the years, an examination into what motivates patients to want to get involved in clinical research has not been done. During our analysis of applications submitted by members of the PLM community, we looked for reasons patients want to participate in research and their overall beliefs about clinical research, in general. In addition, we analyzed obstacles and barriers toward patients’ research participation. We observed the following:Patients are typically motivated by their individual needs and are most interested in research specific to their own condition.To get the most from patients’ involvement and to enhance patients’ contribution towards research goals, researchers should explain the research goal and requirements of each goal in clear and transparent terms, making it easy for patients to understand, thus avoiding any potential miscommunication. Future studies are needed to determine the best methods for involving patients in clinical research. Background Historically, throughout the clinical and medical research arenas, patients have been perceived as passive “subjects” rather than as individuals who may have thoughts regarding research development, research plans, implementation of research studies, and data analysis. However, it is becoming more clear that patients increasingly want to have a more active role in clinical research studies and in the management of their own medical conditions as evidenced by a “no decision about us without us” stance, meaning patients want to make informed decisions about their health while working alongside their healthcare professionals. The central aim of this research study was to determine patients’ motivations for being involved in research design and understand their perceptions of current research practices. Methods Two independent qualitative studies were conducted. In Study 1, we analyzed applications submitted by self-identified patients from within the PatientsLikeMe (PLM) community, for acceptance onto our advisory panel. The advisory panel was tasked with developing a best practice guide for how to involve patients in research. During the qualitative analysis, we identified major reasons for and topics of interest associated with PLM members’ motivation to apply to the advisory panel. In Study 2, we analyzed applications from PLM community members and from patients outside the PLM community for a patient-led patient-reported-outcome (PRO) development project. Similar to Study 1, we identified themes associated with patients’ motivations to participate in developing a new PRO. Results PLM members are interested in being involved in medical research for various reasons, including facilitating provider-patient communication, improving comprehension of medical information, understanding their disease, and bringing a more individualized approach to health care in general. Conclusion Challenges in the process of appropriate involvement of patients in research are discussed. In both studies, the applicants shared their interests in being involved in research. However, in Study 2, many of the patients shared ideas that were not appropriate for the development of a PRO, which indicated limitations in how the invitation and application explained the project to patients. Future studies should contribute to determining the most appropriate method for involving patients in various settings.

This study is the first demonstration of the effect of motivational focus (approach vs. avoidance) on the interpretation of graphical view of personal data, specifically, weight loss progress. In two experiments, participants were randomly assigned to see the bogus weight loss data charted against either a goal or a baseline reference line. In the first experiment, we accessed participants' chronic motivational focus. In the second study, we primed motivation by exposing the participants to either a gain- or loss-focused health message. The results demonstrate that participants with either chronic or manipulated approach motivation predicted higher future weight loss in the goal reference line condition than in the baseline reference line condition. The opposite pattern was observed for participants with either chronic or manipulated avoidance motivation. The potential of matching graphical data display to personality characteristics to promote effective health management is discussed. © 2012 Copyright Taylor and Francis Group, LLC.

Background: The goal of this study is to identify betting patterns displayed during the first month of actual Internet gambling on a betting site that can serve as behavioural markers to predict the development of gambling-related problems. Methods: Using longitudinal data, k-means clustering analysis identified a small subgroup of high-risk gamblers. Results: Seventy-three percent of the members of this subgroup eventually closed their account due to gambling-related problems. The characteristics of this high-risk subgroup were as follows: (i) frequent and (ii) intensive betting combined with (iii) high variability across wager amount and (iv) an increasing wager size during the first month of betting. Conclusion: This analysis provides important information that can help to identify potentially problematic gamblers during the early stages of gambling-related problems. Public health workers can use these results to develop early interventions that target high-risk Internet gamblers for prevention efforts. However, one study limitation is that the results distinguish only a small proportion of the total sample; therefore, additional research will be necessary to identify markers that can classify larger segments of high-risk gamblers.

Using actual gambling behavior provides the opportunity to develop behavioral markers that operators can use to predict the development of gambling-related problems among their subscribers. Participants were 4,056 Internet gamblers who subscribed to the Internet betting service provider bwin.party. Half of this sample included multiple platform gamblers who were identified by bwin.party's Responsible Gambling (RG) program; the other half were controls randomly selected from those who had the same first deposit date. Using the daily aggregated Internet betting transactions for gamblers' first 31 calendar days of online betting activities at bwin.party, we employed a 2-step analytic strategy: (a) applying an exploratory chi-squared automatic interaction detection (CHAID) decision tree method to identify characteristics that distinguished a subgroup of high-risk Internet gamblers from the rest of the sample, and (b) conducting a confirmatory analysis of those characteristics among an independent validation sample. This analysis identified two high-risk groups (i.e., groups in which 90% of the members were identified by bwin.party's RG program): Group 1 engaged in three or more gambling activities and evidenced high wager variability on casino-type games; Group 2 engaged in two different gambling activities and evidenced high variability for live action wagers. This analysis advances an ongoing research program to identify potentially problematic Internet gamblers during the earliest stages of their Internet gambling. Gambling providers and public policymakers can use these results to inform early intervention programs that target high-risk Internet gamblers.

e21608Background: The objective of this study was to compare the self-reported disease burden and experiences of patients with advanced non-small cell lung cancer (NSCLC) who reported considerable ...

This article presents findings from the first taxometric study of actual gambling behavior to determine whether we can represent the characteristics of extreme gambling as qualitatively distinct (i.e., taxonic) or as a point along a dimension. We analyzed the bets made during a 24-month study period by the 4,595 most involved gamblers among a cohort of 48,114 people using an Internet service to gamble on sporting events. We applied two taxometric procedures (i.e., MAMBAC and MAXCOV) to three indicators of betting behavior: total money lost, total number of bets, and total money wagered. The results fail to provide support for the view that the most involved Internet sports gamblers include a distinct category of gamblers. More research is necessary to clarify the similar features of recreational and extreme gamblers and the dimensions that scientists can use to measure these behaviors. Finally, we discuss the implications of these findings for clinical, research, and public policy activities.

We developed an educational website for parents of paediatric patients with kidney diseases in Russia. Parents could ask questions regarding their child's illness and submit information, including medical summaries and scanned or electronic images. A US-trained specialist in paediatric nephrology reviewed the information provided and advised about further evaluation or referral, as well as discussing possible treatment plans. In the first nine months, 141 distinct users communicated through the website. Fifty-eight percent of patients were female. An analysis of 70 cases suggested that in 45% there had been overdiagnosis of common paediatric problems, such as urinary tract infection and pyelonephritis. Users completed an anonymous satisfaction survey. The response rate was 84% ( n = 59/70). The majority of respondents found the consultation useful (mean = 4.6 on a 5-point scale). The online consultation answered the questions of most respondents, provided useful information and relieved uncertainty regarding a follow-up. The majority of the respondents (>90%) confirmed that they trusted the online consultation and would recommend the technique to other parents. Online consultation for parents can provide reliable information that results in improved parental satisfaction and education. This approach may be useful in improving care and providing patient education in underserved areas in the USA and elsewhere.

The prevalence, morbidity and mortality of hypertension are strikingly higher for African Americans than for Whites. Poor adherence to the antihypertensive medication regimen is a major cause of inadequate blood pressure control. In this study, we assess the relationship of antihypertensive medication adherence to sociodemographic, clinical and cognitive characteristics of urban African American adults.Data were drawn from a larger randomized controlled trial assessing the effect of a behavioral intervention to improve medication adherence and blood pressure control among hypertensive African American patients followed in an urban primary care network. Medication adherence was assessed at baseline using the Medication Event Monitoring System (MEMS)--a method regarded as the gold standard for assessing medication adherence in clinical research. Information on potential correlates of medication adherence (sociodemographic, clinical and cognitive) was obtained at baseline by computer-assisted interview. We assessed the cross sectional association of these factors to medication adherence in baseline data.Medication adherence was significantly associated with systolic blood pressure (r=.253, P.04) and self-reported medication adherence (r=.285, P.03). The relationship of education to medication adherence varied significantly by sex (P.05 for interaction). Specifically, lower educational attainment was related to higher adherence among men, but lower adherence among women.Identifying correlates of low antihypertensive medication adherence and their interactions, as in this study, will help health providers to better recognize patients at higher risk for worse hypertension-related outcomes. This knowledge can also inform interventions which target a higher-risk subset of hypertensive patients.