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In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) had significantly higher rates of organ and hematologic response compared with patients who received VCd alone. Here, we present patient-reported outcomes (PROs) from the ANDROMEDA trial. PROs were assessed through cycle 6 using three standardized questionnaires. Treatment effect through cycle 6 was measured by a repeated-measures, mixed-effects model. The magnitude of changes in PROs versus baseline was generally low, but between-group differences favored the D-VCd group. Results were generally consistent irrespective of hematologic, cardiac, or renal responses. More patients in the D-VCd group experienced meaningful improvements in PROs; median time to improvement was more rapid in the D-VCd group versus the VCd group. After cycle 6, patients in the D-VCd group received daratumumab monotherapy and their PRO assessments continued, with improvements in health-related quality of life (HRQoL) reported through cycle 19. PROs of subgroups with renal and cardiac involvement were consistent with those of the intent-to-treat population. These results demonstrate that the previously reported clinical benefits of D-VCd were achieved without decrement to patients' HRQoL and provide support of D-VCd in patients with AL amyloidosis.

Objectives This study aimed to develop and assess the content validity of a patient-reported outcomes (PROs) instrument to measure symptoms and impacts experienced by patients with active multiple myeloma (MM). Methods The PRO instrument was developed using an iterative, mixed-methods approach. The list of concepts was generated based on a review of existing evidence (qualitative studies and literature) and post hoc psychometric evaluations of 2 PRO instruments in 3 clinical trials. A total of 30 adult patients with MM from the United States participated in hybrid concept elicitation/cognitive debriefing interviews to validate the content validity of the newly developed PRO instrument. Translatability assessment was completed in 8 languages. Results The item generation process resulted in 17 symptom and 9 impact concepts for evaluation. The concept elicitation interviews and analysis were based on the first 25 participants; evidence of saturation was observed. The cognitive debriefing interviews and analysis were based on the last 23 participants across 4 waves of interviews. On the basis patient feedback, 10 items were removed, and 1 item was added to the PRO instrument. The translatability assessment resulted in 1 minor revision. The multiple myeloma symptom and impact questionnaire (MySIm-Q) includes 11 symptom and 6 impact concepts, organized within 8 hypothesized subdomains, with each concept measured using a 5-point verbal rating scale and a 7-day recall period. Conclusions The MySIm-Q instrument was developed using rigorous and mixed methodology and with direct input from patients who received a diagnosis of MM. The MySIm-Q has good content validity and is culturally relevant for use in global clinical trials.

In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009.

In the phase 3 APOLLO trial, daratumumab in combination with pomalidomide and dexamethasone (D-Pd) significantly reduced the rate of disease progression or death by 37% relative to Pd alone in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. Here, we present patient-reported outcomes (PROs) from APOLLO. Median treatment duration was 11.5 months with D-Pd and 6.6 months with Pd. PRO compliance rates were high and similar in both groups. No changes from baseline were observed for EORTC QLQ-C30 global health status scores in either group, while physical and emotional functioning, disease symptoms, and adverse effects of treatment remained at baseline levels with D-Pd but worsened with Pd. Reductions (p, The APOLLO study was sponsored by the European Myeloma Network (EMN) in collaboration with Janssen Research & Development, LLC. Medical writing and editorial support were provided by Justine Lempart, PhD, and Linda V. Wychowski, PhD, of Eloquent Scientific Solutions and were funded by Janssen Global Services, LLC

Background: Systemic AL amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys; there are currently no health authority-approved treatments. Therapies for the treatment of multiple myeloma (MM), including bortezomib, cyclophosphamide, and dexamethasone (VCd), have been shown to improve outcomes in AL amyloidosis, but more effective therapies are needed to achieve deep and rapid hematologic responses, reverse amyloid-mediated organ dysfunction, and improve overall survival. Daratumumab is an anti-CD38 monoclonal antibody approved as monotherapy or in combination with other agents for the treatment of MM. ANDROMEDA (NCT03201965) is a randomized, open-label, active-controlled phase 3 trial of VCd ± daratumumab subcutaneous (DARA SC) in patients with newly-diagnosed AL amyloidosis. After a median follow-up of 11.4 months, the complete hematologic response rate was 53% for DARA SC + VCd (DARA-VCd) and 18% for VCd (odds ratio, 5.1; 95% CI, 3.2-8.2; P Methods: Patients with newly-diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage (Mayo 2004) I-IIIA, eGFR ≥20 mL/min, and absence of symptomatic MM were randomized 1:1 to DARA-VCd or VCd and treated for six 28-day cycles; thereafter, patients in the DARA-VCd group received DARA SC alone every 4 weeks for up to 24 cycles. PROs were assessed on Day 1 of Cycles 1-6 for both treatment groups and every 8 weeks thereafter in the DARA-VCd group. PRO assessments included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30), the EuroQol 5-dimensional descriptive system (EQ-5D-5L), and Short Form-36 (SF-36). Improvements in EORTC QLQ-C30 global health status (GHS) and fatigue scale scores and SF-36 mental component summary (MCS) score were secondary endpoints. Assessment of physical functioning, symptom improvement, functional improvement, and health utility as measured by the SF-36, EORTC QLQ-C30 with supplemental symptom items, and the EQ-5D-5L were exploratory outcomes. Patients completed PRO questionnaires prior to study assessments or study drug administration. Analyses of PROs were performed on the intent-to-treat analysis set; patients without a baseline or post-baseline assessment were censored at date of randomization. Compliance with PRO assessments was calculated as the number of assessments received divided by the number of assessments expected at each time point. Descriptive statistics are provided for all PRO endpoints at each time point by treatment group. A distribution-based method was used to define worsening/improvement in scores. Time to worsening/improvement, hazard ratios, and associated 95% confidence intervals were estimated using Kaplan Meier methods and Cox proportional hazards regression. Change from baseline at each time point up to Cycle 6 (Week 24) was calculated using a mixed effects model with repeated measures with patients as a random effect and baseline value, treatment group, time (weeks), treatment-by-time interaction, and stratification factors as fixed effects. Results: A total of 388 patients were randomized (DARA-VCd, n=195; VCd, n=193). Compliance rates for all PRO questionnaires were >90% at baseline and >83% through Cycle 6. Median time to improvement was shorter and median time to worsening was longer in the DARA-VCd group than in the VCd group for EORTC QLQ-C30 GHS and fatigue scales and EQ-5D-5L visual analog scale (VAS) (Table 1). Least squares mean scores for EORTC QLQ-C30 GHS and fatigue, EQ-5D-5L VAS, and SF-36 MCS remained stable in the DARA-VCd group but worsened compared with baseline in the VCd group; between-group differences are shown in Table 2. The greatest between-group differences in PRO score changes from baseline were observed at Week 16 (Cycle 4). After Cycle 6, patients in the DARA-VCd group reported improvements in mean GHS and fatigue scores that continued while on treatment (Figure). Conclusions: Patients with AL amyloidosis treated with DARA-VCd experienced clinical improvements without any decrement in health-related quality of life over 6 cycles. Following Cycle 6, improvements in GHS and fatigue were reported in patients in the DARA-VCd group. These findings further support the value of DARA-VCd in patients with AL amyloidosis. Disclosures Sanchorawala: UpToDate: Patents & Royalties; Abbvie: Other: advisory board; Proclara: Other: advisory board; Caleum: Other: advisory board; Regeneron: Other: advisory board; Oncopeptide: Research Funding; Caelum: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Minnema:Servier: Consultancy; Amgen: Consultancy; Kite, a Gilead Company: Speakers Bureau; Celgene: Other: travel support, Research Funding. Jaccard:Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding; Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding. Lee:Janssen: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding. Gibbs:Janssen, BMS/Celgene, Amgen, Takeda, Pfizer, Caelum, Abbvie and Eidos: Membership on an entity's Board of Directors or advisory committees. Mollee:Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding. Schönland:Janssen: Honoraria, Other: travel support to meetings, Research Funding; Prothena: Honoraria, Other: travel support to meetings, Research Funding; Takeda: Honoraria, Other: travel support to meetings, Research Funding. Suzuki:Bristol-Myers Squibb, Celgene and Amgen: Research Funding; Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria. Kim:BMS, Takeda, Amgen, Celgene, Janssen: Consultancy, Honoraria, Research Funding. Cibeira:Janssen, Akcea Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen, Celgene, Amgen: Honoraria, Other: Educational lectures. Beksac:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Valent:Celgene: Other: Teaching, Speakers Bureau; Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Amgen Inc.: Other: Teaching, Speakers Bureau. Wong:GSK: Research Funding; Roche: Research Funding; Janssen: Research Funding; Bristol Myers Squibb: Research Funding; Fortis: Research Funding; Amgen: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees. Rosenzweig:Janssen: Speakers Bureau. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Qin:Janssen: Current Employment. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Comenzo:Caleum: Consultancy; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Karyopharm: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria. Wechalekar:Takeda: Honoraria, Other: Travel; Celgene: Honoraria; Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory.

Introduction While it is generally believed that people living with more severe obesity experience greater negative impacts on health-related quality of life (HRQoL), their experience may be impacted by other factors such as age, gender, and type 2 diabetes mellitus (T2DM). Methods The 36-Item Short Form Health Survey physical component score and mental component score, Work Productivity and Activity Impairment, and Patient Activation Measure® data from the 2018 National Health and Wellness Survey were analyzed in adults by body mass index (BMI) categories (normal weight: ≥18.5

Relapsed refractory multiple myeloma (RRMM) is a disease that is nonresponsive or progressive on therapy, and although patients can achieve remission, relapse is common. As more treatment options become available for multiple myeloma (MM), it is important to understand patients' experiences of current and emerging therapies.This study aimed to better understand patient experiences with treatment and therapies for MM using qualitative interviews and patient-reported information (PRI) shared on social media.Semistructured qualitative interviews were conducted with adults with RRMM who resided in the United States. In addition to the interviews, PRI was collected from YouTube and a patient advocacy website. Key themes from the interviews and PRI were summarized, and illustrative quotes were extracted.Twenty participants were interviewed; 11 were female, and mean (standard deviation) age was 60 (7.0) years. The PRI included 14 posts and 19 unique contributors (10 were female). Similar treatment-related symptoms were reported in the interviews and PRI. Fatigue and pain were the most frequently reported symptoms while receiving treatment in both the interviews and PRI. These symptoms had a meaningful impact on health-related quality of life (HRQOL); being off treatment and returning to normal living was described as an ideal treatment outcome. Nearly all interview participants (n = 18) preferred a treatment that would allow for a treatment-free interval, if it had the same efficacy and safety profile as a continuous treatment.The symptom experience reported in this study is consistent with known RRMM symptoms and HRQOL impacts. Additionally, this study highlighted that patients' treatment expectations are changing relative to their past treatment experience. Individuals living with RRMM strongly desire therapies with a treatment-free interval and minimal impact on their HRQOL.

Background: Patients (pts) with multiple myeloma (MM) experience health-related quality of life (HRQoL) decrement due to symptoms such as fatigue, pain, and insomnia. Pt perspectives of their disease and treatment expectations can help inform clinical decision-making. The phase 1b/2 CARTITUDE-1 study (NCT03548207) is evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in pts with relapsed/refractory (R/R) MM. An exploratory objective is to describe pretreatment goals and expectations and post-treatment experience of cilta-cel using qualitative interviews. Methods: Pts (aged ≥18 years) with an MM diagnosis per International Myeloma Working Group criteria who had received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and who had received an anti-CD38 antibody were included. On Day 1, cilta-cel (target dose 0.75×106 [range 0.5-1.0×106] CAR+ viable T cells/kg) was given as a single infusion 5-7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). In the phase 2 portion, pts had the option to participate in structured qualitative interviews conducted pretreatment, at Day 100 ± 30 (end of cilta-cel post-infusion period), and Day 184 ± 30 (during post-treatment phase). Pretreatmentinterviews: pts were asked open-ended questions about their experience living with MM and expectations of cilta-cel. Day 100and184interviews: pts were asked about changes to their MM symptoms and daily life impacts, experiences with cilta-cel, and if pretreatment expectations were met. Content analysis of qualitative data was performed by extracting themes from the transcripts based on a coding dictionary. Results: Of 68 pts in the phase 2 portion, 36 (55.6% male; median age: 62.5 years [range: 46-77]) completed ≥1 interview (pretreatment: n=27; Day 100: n=23; Day 184: n=24); 24 pts completed >1 interview and 14 completed all 3 interviews. The most common symptoms reported at the pretreatment interview, pain (85.2% of pts) and fatigue (74.1% of pts), were also frequently considered to have the greatest impact on pts' lives (29.6% and 25.9%, respectively) and identified as symptoms that pts would most like to see improved (25.9% and 33.3%, respectively). After cilta-cel therapy, at Day 100 and 184 interviews, respectively, the proportions of pts who reported pain (21.7% and 29.2%) and fatigue (34.8% and 20.8%) decreased. At the pretreatment interview, pts most frequently reported that MM impacted relationships (92.6%), psychological and emotional functioning (88.9%), and activities of daily living (66.7%). In longitudinal analyses of pts who completed >1 interview, most pts reported either improvement or no change in these impacts at Day 100 and 184 interviews, respectively, (relationships [50.0% and 58.3%], psychological and emotional functioning [77.3% and 83.3%], and activities of daily living [59.1% and 62.5%]), suggesting a diminished impact of MM on HRQoL following cilta-cel treatment. The most common expectations of cilta-cel reported by pts at the pretreatment interview were remission (40.7%), extended life expectancy (14.8%), less treatment (11.1%), and cure (11.1%). The most frequently reported treatment hopes were remission (40.7%), return to perceived normalcy (25.9%), cure (25.9%), and extended life expectancy (22.2%). Key areas in which pts would consider changes to be meaningful with cilta-cel treatment were improved MM symptoms (70.4%), return to perceived normalcy (40.7%), and the ability to be more physically active (33.3%). At Day 100 and 184 interviews, respectively, 78.3% and 91.7% of pts reported that their expectations of cilta-cel were met or exceeded (Figure A). Furthermore, most pts at the Day 100 and 184 interviews (52.2% and 70.8%, respectively) perceived their experience with cilta-cel as exclusively better than their previous treatment experiences (Figure B). Conclusions: Pts treated with cilta-cel experienced reductions in both symptoms associated with R/R MM and impact of MM on HRQoL. Pretreatment expectations of cilta-cel were met or exceeded, and most pts reported their experience was better than with prior MM treatments. Disclosures Cohen: Novartis: Other: Patents/Intellectual property licensed, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Hari:GSK: Consultancy; Amgen: Consultancy; Incyte Corporation: Consultancy; Janssen: Consultancy; BMS: Consultancy; Takeda: Consultancy. Htut:City of Hope Medical Center: Current Employment. Berdeja:CURIS: Research Funding; Constellation: Research Funding; Janssen: Consultancy, Research Funding; Vivolux: Research Funding; Abbvie: Research Funding; Amgen: Consultancy, Research Funding; Poseida: Research Funding; Kesios: Research Funding; EMD Sorono: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Legend: Consultancy; Kite Pharma: Consultancy; Acetylon: Research Funding; Prothena: Consultancy; Celgene: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Teva: Research Funding; Servier: Consultancy; Takeda: Consultancy, Research Funding; Cellularity: Research Funding; Lilly: Research Funding; Bluebird: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Bioclinica: Consultancy; Karyopharm: Consultancy. Madduri:Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; AbbVie: Consultancy, Honoraria. Usmani:Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Research Funding; Pharmacyclics: Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Merck: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Array Biopharma: Research Funding. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Crawford:RTI Health Solutions: Current Employment. Morrison:RTI Health Solutions: Current Employment. Doward:RTI Health Solutions: Current Employment. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.

PURPOSE To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study. PATIENTS AND METHODS PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs. RESULTS A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( P = .0007 v Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score. CONCLUSION D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.

Background In the phase III ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) significantly improved overall response rate and progression-free status compared with VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Here, we present patient-reported outcomes (PROs) from ALCYONE. Methods The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaire were administered at baseline, every 3 months (year 1) and every 6 months (until progression). Treatment effects were assessed using a repeated-measures, mixed-effects model. Results Compliance with PRO assessments was comparable at baseline (> 90%) and throughout study (> 76%) for both treatment groups. Improvements from baseline were observed in both groups for EORTC QLQ-C30 Global Health Status (GHS), most functional scales, symptom scales and EQ-5D-5L visual analog scale (VAS). Between-group differences were significant for GHS (p = 0.0240) and VAS (p = 0.0160) at month 3. Improvements in pain were clinically meaningful in both groups at all assessment time points. Cognitive function declined in both groups, but the magnitude of the decline was not clinically meaningful. Conclusions Patients with transplant-ineligible NDMM demonstrated early and continuous improvements in health-related quality of life, including improvements in functioning and symptoms, following treatment with D-VMP or VMP. Trial registration ClinicalTrials.gov identifier NCT02195479, registered September 21, 2014

Background Physiological and behavioral factors including hunger, satiety, food intake, and cravings are health determinants contributing to obesity. Patient-reported outcome (PRO) measures focused on eating-related factors provide insight into the relationships between food choice and quantity, weight change, and weight-loss treatment for individuals living with obesity. The DAILY EATS is a novel 5-item, patient-reported measure evaluating key eating-related factors (Worst and Average Hunger, Appetite, Cravings, and Satiety). Methods Psychometric analyses, consistent with regulatory standards, were conducted to evaluate the DAILY EATS using data from two randomized trials that included individuals with severe obesity without diabetes (NCT03486392) and with severe obesity and type 2 diabetes (NCT03586830). Additional measures included Patient Global Impression of Status (PGIS) and Patient Global Impression of Change items, Impact of Weight on Quality of Life-Lite, Ease of Weight Management, and Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8b and 10a. The reliability, validity, and responsiveness of the DAILY EATS were assessed, and a scoring algorithm and thresholds to interpret meaningful score changes were developed. Results Item-level analyses of the DAILY EATS supported computation of an Eating Drivers Index (EDI), comprising the related items Worst Hunger, Appetite, and Cravings. Internal consistency (Cronbach’s coefficient alphas ≥0.80) and test-retest reliability (coefficients > 0.7) of the EDI were robust. Construct validity correlation patterns with other PRO measures were as hypothesized, with moderate to strong significant correlations between the EDI and PGIS-Hunger (0.30 ≤ r ≤ 0.68), PGIS-Cravings (0.33 ≤ r ≤ 0.77) and PGIS-Appetite (0.52 ≤ r ≤ 0.77). Anchor- and distribution-based analyses support reductions ranging from 1.6 to 2.1 as responder thresholds for the EDI, representing meaningful within-person improvement. Conclusions The DAILY EATS individual items and the composite EDI are reliable, sensitive, and valid in evaluating the concepts of hunger, appetite, and cravings for use in individuals with severe obesity with or without type 2 diabetes.

Background Smoldering multiple myeloma (SMM) is an early form of multiple myeloma (MM). SMM is typically considered asymptomatic, and research on how it affects health-related quality of life (HRQoL) is limited. This study assessed the symptoms and HRQoL of patients with SMM and those who progressed from SMM to MM and evaluated the content validity of two patient-reported outcome instruments (EORTC QLQ-C30 and nine items from the EORTC QLQ-MY20) for use in SMM clinical trials. To address these objectives, concept elicitation and cognitive interviews were conducted with SMM patients and recently diagnosed MM patients. Results Fifteen adult SMM and six adult MM participants with a prior SMM diagnosis were interviewed. On average, SMM study participants were 61 years old (46.0–78.0), 11 (73%) were female, and diagnosed 2.6 (±2.0) years ago. Each participant had experienced at least one symptom, most commonly tiredness/fatigue, weakness, and pain. The most common HRQoL impacts were emotional and physical. SMM study participants demonstrated good understanding of both the EORTC QLQ-C30 and EORTC QLQ-MY20 subscales and found them relevant to their SMM health state. The average age of MM participants was 53 years old (39.0–62.0); 5 (83%) were female and diagnosed 1.9 years ago (±2.1). MM participants most commonly reported tiredness, weakness, constipation, shortness of breath, and dry mouth as occurring when they progressed from SMM to MM. Conclusions Although previously described as asymptomatic, these SMM participants reported experiencing symptoms that affected their lives. Additionally, the EORTC subscales measured symptoms SMM patients experienced. The participants with MM reported that the symptom burden and HRQoL impacts increased when diagnosed with MM. These findings suggest the need for increased surveillance of symptoms within the SMM population and further suggest that the EORTC subscales can be used to assess symptoms and impacts in both the SMM and MM populations.

In the phase III CASTOR trial, daratumumab, bortezomib and dexamethasone (D-Vd) significantly extended progression-free survival compared with bortezomib and dexamethasone (Vd) alone in patients with relapsed/refractory multiple myeloma (RRMM). Here, we present patient-reported outcomes (PROs) from the CASTOR trial. PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system questionnaire. Treatment effects through Cycle 8 were measured by a repeated measures mixed-effects model. After Cycle 8, PROs were only collected for patients in the D-Vd group who continued on daratumumab monotherapy. Compliance rates for PRO assessments were high and similar between treatment groups. Mean changes from baseline were generally similar between treatment groups for EORTC QLQ-C30 global health status (GHS), functioning and symptoms, and did not exceed 10 points for either treatment group. Subgroup analyses were consistent with the results observed in the overall population. There was no change in patients' health-related quality of life for the first eight cycles of therapy; thereafter, patients treated with daratumumab over the long-term reported improvements in GHS and pain. These results complement the significant clinical benefits observed with D-Vd in patients with RRMM and support its use in this patient population.

Summary Background In part 1 of the two-part CASSIOPEIA study, treatment before and after autologous haematopoietic stem-cell transplantation (HSCT) with daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) significantly improved rates of stringent complete response and progression-free survival versus bortezomib, thalidomide, and dexamethasone (VTd) in patients with newly diagnosed multiple myeloma. Methods CASSIOPEIA is an ongoing randomised, open-label, active-controlled, parallel-group, phase 3 trial done at 111 academic and community practice centres in Europe. Transplantation-eligible adults with newly diagnosed multiple myeloma were randomly assigned (1:1) to D-VTd or VTd. Treatment consisted of four 28-day cycles of induction therapy before autologous HSCT and two 28-day cycles of consolidation therapy after. In this prespecified secondary analysis, patient-reported outcomes were assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire-core 30-item (EORTC QLQ-C30) and EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaire at baseline, after induction (cycle 4, day 28), and after consolidation (day 100 after autologous HSCT). The analysis was done in all patients in the intention-to-treat population with a baseline and at least one post-baseline patient-reported outcome assessment. The trial is registered at ClinicalTrials.gov ( NCT02541383 ). Findings Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled and randomly assigned D-VTd (n=543) or VTd (n=542). Questionnaire completion rates were high at baseline (511 [94%] of 543 in the D-VTd group vs 510 [94%] of 542 in the VTd group). Compliance rates (calculated from the number of completed surveys as a proportion of the predicted number of participants still on study treatment) were high at post-induction (431 [84%] of 513 vs 405 [80%] of 509) and post-consolidation (414 [90%] of 460 vs 386 [88%] of 438) assessments and were similar between treatment groups. Mean changes in global health status scores from baseline to post-induction were not different between the D-VTd group (3·8 [95% CI 1·6 to 6·0]) and VTd group (2·9 [0·7 to 5·1]; p=0·43), or from baseline to post-consolidation between the two groups (D-VTd group, 9·7 (95% CI 7·4 to 11·9) vs VTd group, 8·7 (6·5 to 11·0; p=0·45). Improvements from baseline in EORTC QLQ-C30 global health status and EQ-5D-5L visual analogue scale scores were observed in post-consolidation scores in both groups. Post-consolidation scores showed significantly greater mean decreases in pain (−23·3 [95% CI −26·6 to −20·0] in the D-VTd group vs −19·7 [−23·0 to −16·3] in the VTd group; p=0·042), significantly smaller reductions in cognitive functioning (−5·0 [−7·6 to −2·4] vs −7·9 [−10·6 to −5·3]; p=0·036), and significantly greater improvements in emotional functioning (13·0 [10·4 to 15·5] vs 9·5 [6·9 to 12·1]; p=0·013) and in constipation (–3·2 [–7·3 to 0·9] vs 1·8 [–2·4 to 6·0]; p=0·025) with D-VTd versus VTd. Between-group differences in change from baseline for all other scales were not significant. Interpretation D-VTd and VTd were associated with on-treatment health-related quality of life improvements from baseline in transplantation-eligible patients with newly diagnosed multiple myeloma. The significantly greater reductions in pain, less deterioration of cognitive functioning, and greater emotional functioning improvements complement the clinical benefits observed with D-VTd versus VTd, and support the addition of daratumumab to standard regimens in patients with newly diagnosed multiple myeloma. Funding Intergroupe Francophone du Myelome, The Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research and Development.

Background Social media platforms give patients a voice by allowing them to discuss their health and connect with others. These unfiltered and genuine reports offer direct access to what matters most to patients. Exploring the patient-reported outcomes discussed in these platforms reveal clinical insights and behavioral patterns of the real-world patient journey. This research study reviewed health-related quality of life (HRQoL) concepts reported by patients with multiple myeloma (MM). Methods Data were obtained using the Belong.life patient-powered research network (PPRN) using social media listening methods. The analysis cohort consisted of adults diagnosed with MM who signed into the Belong.life platform by June 2018. Natural language processing and medical neural networks were utilized to extract text data to mine and scan for concepts using programmed algorithms. The textual review of the data was conducted on two levels: the over-arching concept of interest (broad symptom and impact classification) and the more specific symptom and impacts report. Concepts were analyzed descriptively and summarized by age, gender, context of report, and stage of disease/treatment journey. Results Two hundred thirty patients with MM from the United States (52%), Israel (42%), Canada (3%), and 3% from Egypt, France, Greece, India, United Kingdom, and Australia were identified. A total of 57% were female and at account registration the median age was 57 years. A total of 126 patients had evaluable text data to search concepts being discussed. The PPRN platform identified 93% of the concepts from the conceptual model developed based on prior literature review. The most commonly reported symptoms were neuropathy, tiredness, nausea, back pain, fatigue, and bone pain. Back pain appeared as the most prominent symptom early in the disease and sometimes occurred prior to MM diagnosis. Tiredness, nausea, fatigue, and bone pain were frequently reported after MM diagnosis, with the start of treatment. Conclusion Patient-oriented social media platforms, such as Belong.life, can capture and contribute to a holistic vision of concepts surrounding patients’ HRQoL. The ability to understand when a certain debilitating symptom appeared and to which sub-population of patients may allow for a personalized approach to treatment, improving adherence and quality of care as well as increasing patient well-being.

Introduction: In oncology clinical trials, overall survival (OS) is considered the gold standard efficacy endpoint. However, in multiple myeloma, the prolonged survival times and availability of multiple salvage therapies render it difficult to rely on OS as a primary endpoint. Instead, progression-free survival (PFS) or clinical response can be a relevant biomarker. At the same time, some health technology assessment bodies will only consider evidence based on patient-relevant endpoints, such as morbidity, mortality, and health-related quality of life (HRQoL), within their benefit assessments. Patient-reported outcomes (PROs) provide insights into how a treatment affects HRQoL, including symptoms and functioning. In the phase 3 MAIA trial, daratumumab, lenalidomide, and dexamethasone (D-Rd) demonstrated a significantly prolonged PFS and rapid and sustained improvements in PROs compared with lenalidomide and dexamethasone (Rd) alone at a median follow-up of 28 months. Updated results with longer follow-up confirmed a continued PFS benefit, deepening best clinical responses, and a significant OS benefit with D-Rd. Here, we report the results of analyses exploring the relationship between clinical efficacy endpoints and PROs in the MAIA trial. Methods: In MAIA (NCT02252172), TIE patients with NDMM were randomized to D-Rd or Rd until disease progression (PD) or unacceptable side effects. Clinical response and PD were defined per the International Myeloma Working Group uniform response criteria. PROs were assessed at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, every 6 months thereafter until PD, or at end of treatment and at 8 and 16 weeks post-progression using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30). The current analyses were conducted on patients with a baseline PRO assessment and ≥1 post-baseline PRO assessment using a clinical cutoff date of February 19, 2021. Patients from both treatment groups were pooled and stratified by best clinical response. For PROs, the threshold for clinically meaningful change from baseline was defined a priori as ≥10 points based on published literature. Analyses were conducted for the global health status (GHS), fatigue, and pain scales of the EORTC QLQ-C30. The proportions of patients with clinically meaningful improvement in these PROs from baseline at any time while on treatment were calculated for and compared across best clinical response subgroups. For this analysis, patients were censored at the time of PD or discontinuation of therapy. Results were summarized with odds ratios and 95% confidence intervals. Additionally, the proportions of patients with clinically meaningful worsening in PROs from baseline at the time of and post-progression were also calculated for those who had PD. No adjustments were made for multiplicity. Nominal P-values are presented. Results: Best clinical response at a median follow-up of 56.2 months for the 710 patients included in this analysis is shown in the Table. For GHS, fatigue, and pain, the proportion of patients who reported clinically meaningful improvement from baseline increased with increasing depth of best clinical response. Odds ratios comparing best clinical response vs stable disease reflect this relationship and are shown in the Figure. Of the 264 patients who experienced PD and had PRO data at the time of or post-progression, 38.6%, 54.9%, and 39.4% reported meaningful worsening of GHS, pain, and fatigue, respectively, at the time of or post-progression. Conclusions: Patients with deeper best clinical response were more likely to report meaningful improvements in PROs. Patients who experienced PD reported worsening of GHS and symptoms at the time of or following progression. These analyses provide evidence of the association between key clinical efficacy endpoints and PROs and demonstrate the patient relevance of these clinical endpoints. Figure 1 Figure 1. Disclosures Perrot: Abbvie: Honoraria; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: 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; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kumar: Amgen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Bluebird Bio: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Plesner: Takeda: Research Funding; Genentech: Other: Advisor, Research Funding; Oncopeptides: Other: Advisor, Research Funding; AbbVie: Other: Advisor, Research Funding; CSL Behring: Other: Advisor; Janssen: Other: Advisor, Research Funding; Celgene: Other: Advisor, Research Funding; Genmab: Research Funding. Orlowski: Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees. Moreau: Abbvie: Honoraria; Oncopeptides: Honoraria; Celgene BMS: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Bahlis: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Honoraria. Nahi: XNK Therapeutics AB: Consultancy. Hulin: abbvie: Honoraria; Celgene/BMS: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Janssen: Honoraria. Quach: Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Goldschmidt: GSK: Honoraria; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Johns Hopkins University: Other: Grant; Mundipharma: Research Funding; MSD: Research Funding; Molecular Partners: Research Funding. O'Dwyer: Bristol Myers Squibb: Research Funding; ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Venner: Amgen: Research Funding; Celgene: Research Funding; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Weisel: Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Macro: Takeda: Honoraria, Other: Travel accomodation, Research Funding; Janssen: Honoraria, Other: Travel accomodation, Research Funding; GSK: Honoraria; Celgen/BMS: Honoraria; Sanofi: Honoraria. Leleu: Sanofi: Honoraria; Roche: Honoraria; Pierre Fabre: Honoraria; Oncopeptides: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Merck: Honoraria; Karyopharm Therapeutics: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Celgene: Honoraria; Gilead Sciences: Honoraria; Janssen-Cilag: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Other: Non-financial support. Liu: Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau: Janssen: Current Employment, Current equity holder in publicly-traded company. Gries: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Ho: DRG Abacus: Consultancy; Emalex Biosciences: Consultancy; Janssen: Consultancy. Mistry: Janssen: Current Employment, Current equity holder in publicly-traded company. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Delioukina: Janssen: Current Employment. Vermeulen: Janssen: Current Employment, Current equity holder in publicly-traded company. Usmani: Amgen: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; SkylineDX: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding.

Introduction: Multiple myeloma (MM) is a chronic hematologic malignancy with a high symptom burden that can have a substantial negative impact on patients' (pts) health-related quality of life (HRQoL). The introduction of novel triplet regimens for newly diagnosed MM (NDMM) has extended progression-free survival (PFS) and overall survival (OS); however, adverse events and demanding administration and monitoring schedules have a further negative effect on HRQoL, especially among pts who are transplant ineligible (TIE) due to older age and/or frailty. Optimizing initial treatment is particularly important in older pts, many of whom receive only 1 line of therapy. The phase 3 MAIA trial compared daratumumab, lenalidomide, and dexamethasone (D-Rd) vs lenalidomide and dexamethasone (Rd) in TIE pts with NDMM. At a median follow-up of 28 months, D-Rd significantly prolonged PFS and was associated with faster and sustained clinically meaningful improvements in patient-reported outcomes (PROs) vs Rd. Results of an updated analysis with longer follow-up recently confirmed a significant benefit in OS with D-Rd vs Rd as well as a continued significant PFS benefit and higher rates of complete response or better and very good partial response or better. Here we present an update of the HRQoL analysis with additional follow-up. Methods: MAIA (NCT02252172) is a randomized, open-label, active controlled, multicenter, phase 3 study of TIE pts with NDMM who were randomly assigned 1:1 to receive D-Rd or Rd until disease progression (PD) or unacceptable toxicity. PROs were recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EQ-5D-5L visual analog scale. EORTC QLQ-C30 has 30 items comprising 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 global health status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaires were completed at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, and every 6 months thereafter until PD. Analyses were conducted on all pts with a baseline and ≥1 post-baseline PRO assessment. Pts were censored at PD or discontinuation of study treatment. Thresholds for meaningful improvement and worsening were defined a priori based on published literature (≥10-point change). Treatment effect was analyzed using a mixed-effects model for repeated measurements including baseline value, visit, treatment, visit by treatment interaction, and randomization stratification factors as fixed effects and individual subject as random effect. Results: At a median follow-up of 56.2 months, discontinuation rates were lower with D-Rd than Rd (56.8% vs 80.8%). For GHS, physical functioning, fatigue, pain, and dyspnea, PROs that are particularly relevant to pts with MM, a numerically greater proportion of pts achieved a meaningful improvement with D-Rd vs Rd (Table 1). Differences were significant for physical functioning, fatigue, and dyspnea. The proportion of pts achieving a meaningful worsening on therapy was similar in both treatment groups (Table 1). The median time to improvement was numerically shorter with D-Rd vs Rd for physical functioning and pain and with Rd vs D-Rd for GHS and fatigue; differences were not significant (Table 2). The median time to worsening of fatigue was similar between groups, numerically longer for D-Rd vs Rd for GHS, and significantly longer with D-Rd than Rd for physical functioning, pain, and dyspnea (Table 2). Median time to worsening of pain with D-Rd vs Rd was 39.43 vs 17.97 months, reflective of an additional ~21 months without worsening pain among pts treated with D-Rd. Between-group differences for least squares mean change from baseline for these 5 PROs favored D-Rd vs Rd at all assessment time points except cycle 3 for physical functioning and cycle 6 for fatigue; differences were significant at ≥1 timepoint for each scale. Conclusions: These updated PRO analyses from the MAIA study demonstrate sustained and clinically meaningful improvements in HRQoL with D-Rd vs Rd with almost 5 years of follow-up. These results are consistent with the clinical benefits of superior PFS, OS, and deep responses observed with D-Rd compared with Rd and support the use of D-Rd in older pts. Figure 1 Figure 1. Disclosures Perrot: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kumar: Roche-Genentech: Consultancy, Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Bluebird Bio: Consultancy; Tenebio: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Plesner: Takeda: Research Funding; Oncopeptides: Other: Advisor, Research Funding; Genentech: Other: Advisor, Research Funding; CSL Behring: Other: Advisor; AbbVie: Other: Advisor, Research Funding; Celgene: Other: Advisor, Research Funding; Janssen: Other: Advisor, Research Funding; Genmab: Research Funding. Orlowski: Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees. Moreau: Oncopeptides: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene BMS: Honoraria; Amgen: Honoraria; Abbvie: Honoraria. Bahlis: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Nahi: XNK Therapeutics AB: Consultancy. Hulin: Takeda: Honoraria; Sanofi: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; abbvie: Honoraria. Quach: CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Goldschmidt: Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; GSK: Honoraria; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. O'Dwyer: ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Bristol Myers Squibb: Research Funding. Venner: BMS: Honoraria; Amgen: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Weisel: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Macro: Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria, Other: Travel accomodation, Research Funding; Janssen: Honoraria, Other: Travel accomodation, Research Funding; Celgen/BMS: Honoraria. Leleu: Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria. Liu: Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau: Janssen: Current Employment, Current equity holder in publicly-traded company. Gries: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Ho: DRG Abacus: Consultancy; Janssen: Consultancy; Emalex Biosciences: Consultancy. Mistry: Janssen: Current Employment, Current equity holder in publicly-traded company. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Delioukina: Janssen: Current Employment. Vermeulen: Janssen: Current Employment, Current equity holder in publicly-traded company. Usmani: Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau.

Background: Multiple myeloma (MM) negatively affects health-related quality of life (HRQoL), and with each relapse, patients with MM experience further declines in HRQoL. Patient-reported HRQoL is therefore an important treatment outcome, in addition to clinical response to therapy. CARTITUDE-1 (NCT03548207) is a phase 1b/2 study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed/refractory (R/R) MM. We evaluated symptoms, functioning, and overall HRQoL through patient-reported outcome measures, which is a secondary objective of CARTITUDE-1. Methods: Patients were ≥18 years of age with a diagnosis of MM per International Myeloma Working Group criteria, measurable disease, and Eastern Cooperative Oncology Group performance status ≤1. Patients had received ≥3 prior regimens for MM or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and had received an anti-CD38 antibody. Cilta-cel was given as a single infusion on Day 1 (target dose: 0.75×106 [range: 0.5-1.0×106] CAR+ viable T cells/kg) 5-7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). In the phase 2 portion of CARTITUDE-1, HRQoL was assessed at baseline, on Days 7, 28, 56, 78, and 100, and every 28 days thereafter using 3 patient-reported instruments: the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30), 4 items from the EORTC QLQ-Multiple Myeloma (MY20) module, and the 5-level EuroQol Five Dimension (EQ-5D-5L) measure. Raw EORTC QLQ-C30 and EORTC QLQ-MY20 scores were linearly transformed to a scale ranging from 0 to 100; the EQ-5D-5L visual analog scale (VAS) score ranges from 0 to 100. Clinically meaningful changes in EORTC QLQ-C30 symptoms, physical functioning, and overall HRQoL were based on anchor-based methods using a patient global impression of change item. Repeated-measures mixed-effects models were used to analyze mean changes in HRQoL from baseline to subsequent assessment time points in patients in the modified intent-to-treat population with ≥1 post-baseline assessment. Median time to event of HRQoL scores was calculated descriptively, using a change in score ≥0.5×standard deviation of values prior to cilta-cel infusion as improvement/worsening with death due to progression defined as worsening. Results: For the 68 patients in the phase 2 portion of CARTITUDE-1 (63.2% male; median age: 62.0 years [range: 43-78]), questionnaire completion rates at baseline and Day 100, respectively, were 92.6% and 69.2% for both the EORTC QLQ-C30 and EORTC QLQ-MY20 items and 92.6% and 70.8% for the EQ-5D-5L. For EORTC QLQ-C30 subscales, clinically meaningful improvements at Day 100 were seen for 71.1% of patients for pain, 62.2% for fatigue, 72.1% for physical functioning, and 51.1% for global health status. Mean changes in pain and fatigue showed a reduction in these symptoms over time (following an initial worsening of fatigue at Day 7; Figure). This trend of improvements over time was also observed for overall HRQoL and EORTC QLQ-MY20 single items. Clinically meaningful improvements at Day 100, defined by a literature-based minimal important difference of 10 points in mean score, were observed for the EORTC QLQ-MY20 single items: thinking about illness and worries about dying or future health. Approximately 50% of the population reported an event of improvement or worsening in EORTC QLQ-C30 and EQ-5D-5L scales, with the rest censored in this early data cut; among these patients, median time to improvement was approximately 1-2 months (with median time to worsening occurring less than 1 month after cilta-cel treatment). There was a trend for an improvement in mean EORTC QLQ-C30 global health status, physical functioning, pain, and fatigue, and EQ-5D-5L VAS at Day 100 with increased depth of response. Conclusions: Some patients with heavily pretreated MM showed rapid and clinically meaningful improvements in pain, fatigue, physical functioning, overall HRQoL, and future perspectives, consistent with their clinical outcomes. With additional follow-up, it is possible that these early improvements in symptoms will translate into greater improvement in overall HRQoL in the long term. Disclosures Martin: Janssen: Research Funding; Sanofi: Research Funding; AMGEN: Research Funding; Seattle Genetics: Research Funding; GSK: Consultancy. Lin:Vineti: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Legend BioTech: Consultancy; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Patents/Intellectual property licensed, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Htut:City of Hope Medical Center: Current Employment. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Hari:GSK: Consultancy; BMS: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Incyte Corporation: Consultancy; Janssen: Consultancy. Berdeja:Teva: Research Funding; Cellularity: Research Funding; Kesios: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; CURIS: Research Funding; EMD Sorono: Research Funding; Genentech, Inc.: Research Funding; Karyopharm: Consultancy; Poseida: Research Funding; Novartis: Research Funding; Lilly: Research Funding; Amgen: Consultancy, Research Funding; Acetylon: Research Funding; Glenmark: Research Funding; Janssen: Consultancy, Research Funding; Vivolux: Research Funding; Takeda: Consultancy, Research Funding; Servier: Consultancy; CRISPR Therapeutics: Consultancy, Research Funding; Constellation: Research Funding; Bluebird: Research Funding; Abbvie: Research Funding; Prothena: Consultancy; Bioclinica: Consultancy; Kite Pharma: Consultancy; Legend: Consultancy. Madduri:Foundation Medicine: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; AbbVie: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Celgene: Consultancy, Honoraria. Usmani:Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; GSK: Consultancy, Research Funding; Abbvie: Consultancy; Array Biopharma: Research Funding; Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.

Background. While weight loss medications commonly target hormones that control hunger and satiety, patients’ interpretations of such concepts and their role in chronic weight management (CWM) are not well documented. Objective. To better understand patients’ perceptions and importance of eating-related concepts in CWM. Methods. In-person interviews were conducted with overweight and obese (BMI > 25.0) adults in the United States with and without type 2 diabetes mellitus. Following open-ended concept elicitation, targeted questions were posed to explore hunger, cravings, appetite, and satiety. Results. Thirty-five individuals with mean BMI of 36.0 (25.7 to 48.7) and 44.9 years of age were interviewed. Participants were mostly white, non-Hispanic, and college educated. Although hunger and cravings were the easiest concepts for participants to define, describe, and differentiate, all four concepts were deemed important in CWM. • Participants commonly described hunger as a physical need to eat and indicated that controlling hunger was key to CWM. Nearly all participants reported they made poorer food choices and/or ate too much if they were too hungry. • Participants defined the feeling of fullness (satiety) after eating as the absence or opposite of hunger. The ability to achieve satiety and stop eating after consuming reasonable portions was frequently reported as key to CWM. • In contrast to hunger, participants defined cravings as a desire (rather than physical need) to eat a specific type of food. While the majority reported that cravings could make it more difficult to lose or maintain a healthy weight, this concept was not as central to CWM as hunger and satiety. • The concept of appetite was generally more difficult for participants to define; however, they commonly noted that having a big appetite implied a significant level of hunger. Nearly all participants reported that appetite, like hunger, influenced food selections and the amount consumed. Conclusions. While the relationships among these four concepts are intertwined, each plays a role in CWM. Specifically, the quantity of food consumed appears to be most influenced by hunger, appetite, and satiety, whereas food selection is generally influenced by hunger, appetite, and cravings.

Patient-centred care is an essential component of high-quality health care, shown to improve clinical outcomes and patient satisfaction, and reduce costs. While there are several authoritative models of obesity pathophysiology and treatment algorithms, a truly patient-centred model is lacking. We describe the development of a patient-centric obesity model. A disease-illness framework was selected because it emphasizes each patient's unique experience while capturing biomedical aspects of the disease. Model input was obtained from an accumulation of research including contributions from experts in obesity and patient-reported outcomes, qualitative research with adults living in the United States, and two targeted literature searches. The model places the patient with obesity at its core and links pathologic imbalances of energy intake and expenditure to environmental, sociodemographic, psychological, behavioural, physiological and medical health determinants. It highlights relationships between obesity signs and symptoms, comorbid conditions, impacts on health-related quality of life, and some barriers to obesity management that must be considered to attain better outcomes. Providers need to evaluate patients holistically, understand what changes each patient is motivated to make, and recognize what challenges might impede weight reduction, improvements in comorbid conditions, signs and symptoms, and health-related quality of life before pursuing individualized treatment goals. Patients living with obesity who do lose weight perceive benefits beyond weight loss. Ideally, this model will increase awareness of the complex, heterogeneous impacts of obesity on patients' well-being and recognition of obesity as a chronic disease, and prompt a call to action among stakeholders to improve quality of care.

Objectives: The advent of large databases, wearable technology, and novel communications methods has the potential to expand the pool of candidate research participants and offer them the flexibility and convenience of participating in remote research. However, reports of their effectiveness are sparse. We assessed the use of various forms of outreach within a nationwide randomized clinical trial being conducted entirely by remote means. Methods: Candidate participants at possibly higher risk for atrial fibrillation were identified by means of a large insurance claims database and invited to participate in the study by their insurance provider. Enrolled participants were randomly assigned to one of two groups testing a wearable sensor device for detection of the arrhythmia. Results: Over 10 months, the various outreach methods used resulted in enrollment of 2659 participants meeting eligibility criteria. Starting with a baseline enrollment rate of 0.8% in response to an email invitation, the recruitment campaign was iteratively optimized to ultimately include website changes and the use of a five-step outreach process (three short, personalized emails and two direct mailers) that highlighted the appeal of new technology used in the study, resulting in an enrollment rate of 9.4%. Messaging that highlighted access to new technology outperformed both appeals to altruism and appeals that highlighted accessing personal health information. Conclusions: Targeted outreach, enrollment, and management of large remote clinical trials is feasible and can be improved with an iterative approach, although more work is needed to learn how to best recruit and retain potential research participants. Trial registration: Clinicaltrials.gov NCT02506244. Registered 23 July 2015. Keywords: Clinical trials, Clinical research, Digital technology, Remote enrollment, Remote monitoring, Outreach

8046 Background: APOLLO (NCT03180736) is a phase 3 trial of pomalidomide and dexamethasone (Pd) ± subcutaneous daratumumab (1800 mg, co-formulated with recombinant human hyaluronidase PH20 in 15 mL) in patients with RRMM and ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. After 16.9 months (mo) median follow-up, D-Pd significantly reduced the rate of progression or death by 37% relative to Pd. Patients with RRMM have reduced HRQoL compared with age- and sex-matched populations. Here, we present PROs from the APOLLO trial. Methods: Patients were randomized 1:1 to D-Pd or Pd and treated in 28-day cycles until disease progression/unacceptable toxicity. PROs were assessed on Day 1 of each cycle using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30), EORTC QLQ Multiple Myeloma Module 20-item (MY20), and EuroQol 5-dimensional descriptive system. PRO analyses were performed on patients from the intent-to-treat population with a baseline (BL) and ≥1 post-BL assessment. Treatment effect was assessed by a mixed effects model with repeated measures. Time to worsening was estimated using the Kaplan-Meier method. Results: A total of 304 patients were included (151 D-Pd, 153 Pd). Median treatment duration was 11.5 mo with D-Pd vs 6.6 mo with Pd. At Cycle 16 (Cyc 16), 63 and 40 patients remained on treatment in the D-Pd and Pd groups, respectively. Compliance rates for PRO instruments were high and comparable between groups. Patients treated with D-Pd had a reduction in pain (maximum improvement: 6.8 points at Cyc 12) measured with the EORTC QLQ-C30 and no mean change in disease symptoms or the treatment side effects subscales of the EORTC QLQ-MY20. Group mean physical and emotional functioning were unchanged from BL with D-Pd but worsened in the Pd group (maximum worsening: 6.4 at Cyc 4 and 9.1 points at Cyc 14). The proportion of patients with a meaningful improvement from BL was 55.0% vs 49.0% for disease symptoms, 43.0% vs 35.3% for physical functioning, and 41.7% vs 31.4% for emotional functioning with D-Pd vs Pd, respectively. Median time to worsening was ̃4 mo, except for the disease symptoms subscale (̃10 mo); there were no differences between groups. Conclusions: When daratumumab was added to Pd, patients did not experience any decrements in HRQoL while on treatment, but some patients experienced reductions in pain as well as clinically meaningful improvements in symptoms and emotional/physical function. These findings complement the clinical benefits of D-Pd in RRMM patients and further support its use in this RRMM population. Clinical trial information: NCT03180736.

Background: Patients with relapsed refractory MM (RRMM) report a decline in HRQOL with disease progression and after each relapse, may experience cumulative toxicities from exposure to several lines of therapy. Social media (SM) platforms are rich databases of unfiltered, real-world evidence, where patients share their experiences about diseases and treatments. These platforms provide researchers with a novel approach to understanding the patient perspective. This study aimed to review unsolicited, publicly available patient-reported information (PRI) shared on SM platforms to gain insights into the patient experience of RRMM and its treatment, specifically CAR-T therapy. Methods: Purposeful sampling of PRI were collected from two SM sources (YouTube [video data] and a patient advocacy website Patient Power [patient blogs; https://patientpower.info]) to identify stories of patients living with RRMM. SM posts were included for review if individuals with a self-reported MM diagnosis described their experience with RRMM and provided commentary on CAR-T therapy. Video/blog data were manually reviewed and content analyzed thematically to address experiences of living with MM, and perceptions and experiences of treatment including CAR-T. Demographic information (e.g., sex and age) were extracted from SM posts along with any accompanying disease information, where data were available. Results: Of 43 posts initially identified from the SM sources, 14 were considered relevant to the study objective: 10 videos / 4 blogs connected to 19 unique patients with RRMM (9 male/10 female, patient age range, 51-72 years). One patient reported receiving CAR-T therapy (female, aged 51 years) and was the subject of 5 videos and all 4 blogs. RRMM Impacts: Key symptoms reported included: pain, fatigue, bone fractures, infections, and fever. Patient-reported HRQOL impacts included reduced mobility, impeded ability to work, negative impact on family activities, low mood, anxiety, and a loss of independence. Patients used different strategies (e.g., slower pace of life, planning, and self-advocacy) to adapt to their progressing disease. Treatment Experience: Patients reported switching from one continuous therapy to another in order to achieve remission with varying degrees of success. Positive treatment outcomes were unpredictable; patients who achieved remission were uncertain how durable the remission period would be and expected to relapse. Treatment Decision Drivers: treatment toxicity, impact on daily life, time required for in-hospital treatment, and desire to attain life milestones. Treatment Outcomes: Patients prioritized HRQOL impacts over effectiveness; benefits of treatment-free periods included ability to travel or attending key life events (e.g., family weddings). CAR-T Patient Experience: Patient reported 16 lines of therapy and two stem-cell transplants but never achieved complete remission from these prior treatments. The CAR-T procedure (received in 2018) was described as quick / preferable to previous treatments (e.g., stem cell transplants / continuous chemotherapy) despite a serious cytokine release storm. The patient experienced a rapid improvement, within 1 month of receiving CAR-T, and achieved complete remission which she described as life changing/lifesaving: remission allowed her to return to living a 'normal' life (i.e., working and exercise) and reportedly reduced the burden on family. Conclusions: This study provides valuable insights on the patient perceptions and experience of MM and its treatments using an innovative method for collecting PRI. Although remission was a key treatment outcome for patients, HRQOL and the ability to live their lives on their own terms were often prioritized over treatment effectiveness. The patient who underwent CAR-T therapy experienced a return to a sense of normality as a result of her CAR-T therapy, if for a brief period, which was life changing for both patient and family. Insights generated from this SM review can be used to inform patient-reported outcome measurement strategies for novel treatment clinical development programs. Purposeful sampling of PRI on 2 SM sources limits external validity of insights gathered. The CAR-T experience was a singular experience of one patient; additional insights are to be learned as more patients undergo CAR-T for their RRMM. Disclosures Crawford: RTI Health Solutions: Current Employment. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Morrison:RTI Health Solutions: Current Employment. Valluri:Janssen: Current Employment. Doward:RTI Health Solutions: Current Employment. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company.

Aim: To assess impact of initial treatment and time-dependent treatment with paliperidone palmitate (PP) versus oral atypical antipsychotics (OAAs) on healthcare resource utilization and costs. Patients & methods: A retrospective longitudinal study was conducted among Medicaid beneficiaries with schizophrenia. Inverse probability treatment weighting method and marginal structural models were used to estimate the impact of treatment on healthcare resource utilization and costs, respectively. Results: Compared to OAAs, PP was associated with lower medical costs (mean monthly cost difference [MMCD] = -US$256; p = 0.008), which offset the higher pharmacy expense (MMCD = US$122; p < 0.001) resulting in nonsignificant cost savings associated with PP (MMCD = -US$91; p = 0.689). Conclusion: PP was associated with comparable overall costs to OAAs, but with significantly lower medical costs, particularly attributable to reduced inpatient visits and long-term care admissions.

Treatment continuity is a major challenge in the long-term management of patients with schizophrenia; poor patient adherence to antipsychotic drugs has been associated with negative clinical outcomes. Long-acting injectable therapies may improve adherence and lessen the risk for psychiatric-related relapse, often leading to rehospitalization and higher healthcare costs. Therefore, understanding the determinants of adherence to antipsychotics is critical in the management of patients with schizophrenia.To assess the impact of baseline patient characteristics on adherence as measured by the Healthcare Effectiveness Data and Information Set (HEDIS) measure of continuity of antipsychotic medications among patients with Medicaid coverage.Medicaid healthcare claims data between 2008 and 2011 from 5 states were used to identify patients who were diagnosed with schizophrenia (aged 25-64 years) and received ≥1 antipsychotic prescriptions in baseline year 2010 and in measurement year 2011. The HEDIS continuity of antipsychotic medications (ie, adherence) measure was defined as the proportion of days covered with any antipsychotic medication ≥80% during the measurement year. The 2 cohorts compared paliperidone palmitate with any other antipsychotics, including quetiapine, risperidone, and haloperidol. The baseline-year characteristics were evaluated as potential predictive factors of adherence in the measurement year using multivariate logistic regressions. The regression models incorporated the inverse probability of treatment weights to control for differences in baseline characteristics between the paliperidone palmitate and the other antipsychotics cohort.Among the 12,990 patients who received an antipsychotic during the study period, 48.6% successfully achieved the continuity criteria in the measurement year. After controlling for other covariates, the odds of adherence were improved by adherence at baseline (odds ratio [OR], 9.42; 95% confidence interval [CI], 8.55-10.39). The use of paliperidone palmitate was associated with a 26% increase in the odds of achieving adherence compared with the use of the other antipsychotics studied (OR, 1.26; 95% CI, 1.14-1.39). In addition, female sex (OR, 1.11; 95% CI, 1.01-1.22), age 55 to 64 years (OR, 1.26; 95% CI, 1.09-1.46) versus age 25 to 34 years, Hispanic race (OR, 1.37; 95% CI, 1.05-1.81) versus white race, and an increase of $10,000 in baseline inpatient costs (OR, 1.11; 95% CI, 1.08-1.15) were associated with greater odds of treatment continuity.In addition to sex, age, and race, the baseline characteristics that were associated with achieving the HEDIS continuity of antipsychotic medication measure included previous-year adherence, inpatient costs, and the use of paliperidone palmitate. These findings offer insight to healthcare plans that cover Medicaid populations on the effects that patient characteristics and treatment types may have on adherence among patients with schizophrenia.

To identify, estimate, and compare 'real world' costs and outcomes associated with paliperidone palmitate compared with branded oral atypical anti-psychotics, and to estimate the threshold rate of oral atypical adherence at which paliperidone palmitate is cost saving.Decision analytic modeling techniques developed by Glazer and Ereshefsky have previously been used to estimate the cost-effectiveness of depot haloperidol, LAI risperidone, and, more recently, LAI olanzapine. This study used those same techniques, along with updated comparative published clinical data, to evaluate paliperidone palmitate. Adherence rates were based on strict Medication Event Monitoring System (MEMS) criteria. The evaluation was conducted from the perspective of US healthcare payers.Paliperidone palmitate patients had fewer mean annual days of relapse (8.7 days; 6.0 requiring hospitalization, 2.7 not requiring hospitalization vs 17.8 days; 12.4 requiring hospitalization, 5.4 not requiring hospitalization), and lower annual total cost ($20,995) compared to oral atypicals (mean $22,481). Because paliperidone palmitate was both more effective and less costly, it is considered economically dominant. Paliperidone palmitate saved costs when the rate of adherence of oral atypical anti-psychotics was below 44.9% using strict MEMS criteria. Sensitivity analyses showed results were robust to changes in parameter values. For patients receiving 156 mg paliperidone palmitate, the annual incremental cost was $1216 per patient (ICER = $191 per day of relapse averted). Inclusion of generic risperidone (market share 18.6%) also resulted in net incremental cost for paliperidone palmitate ($120; ICER = $13). Limitations of this evaluation include use of simplifying assumptions, data from multiple sources, and generalizability of results.Although uptake of LAIs in the US has not been as rapid as elsewhere, many thought leaders emphasize their importance in optimizing outcomes in patients with adherence problems. The findings of this analysis support the cost-effectiveness of paliperidone palmitate in these patients.

Schizophrenia affects ∼1.1% of the United States population, resulting in substantial direct, indirect and societal costs.To evaluate hospitalization rates associated with use of paliperidone palmitate (PP).Data were from a variable-duration double-blind (DB), randomized, relapse-prevention comparison (NCT00111189) of PP vs. placebo (Pbo), followed by a 1-year open-label extension (OLE). Between-phase change in schizophrenia-related hospitalizations was evaluated using data from an investigator-completed questionnaire. Change in hospitalizations using patients before enrollment who participated in the OLE phase was also analyzed. Poisson regression was used to evaluate changes in incidence density within exposure category and by schizophrenia duration.A total of 160 patients in the PP-PP group and 153 in the Pbo-PP group from the DB to the OLE phase were included. Mean age (standard deviation [SD]), gender, and duration of schizophrenia were similar at the start of the DB phase (Pbo: 38.5 years [10.6], 51.0% male, 68.0% ≥5 years' duration; PP: 37.3 years [11.4] (p = 0.342); 51.9% male (p = 0.874); 70.0% ≥5 years' duration (p = 0.698), respectively. From the DB to the end of the OLE phase, the number of hospitalizations per person-year for patients treated during the DB phase with Pbo significantly declined from 0.27 to 0.06 (78% reduction; p = 0.005). A statistically nonsignificant difference was observed for PP patients treated during the DB phase with PP (0.11-0.04; 63.6% reduction; p = 0.076), compared with the OLE phase. Change from before enrollment to the end of the OLE phase (n = 381) produced similar results (0.35-0.04; 88.6% reduction; p 0.001). Patients who enroll in a clinical trial may be different from the general population and this may affect the generalizability of results.From the double-blind to the open-label phase and from prior to the trial until the end of the open-label phase, hospitalizations significantly decreased for patients with schizophrenia treated with PP.

Introduction: Measuring patient-reported outcomes (PROs) in oncology clinical trials is important to capture the patient perspective on quality of survival and the outcomes of health-related quality of life (HRQoL), symptoms, and functional status. In multiple myeloma (MM) randomized clinical trials (RCTs) the common PRO instruments include the EORTC QLQ-C30 and the EQ-5D as generic measures of a patient's health status. While these legacy PRO instruments have been widely used in the MM population, it is important to continue to assess the instruments psychometric properties for the specific context of use and target population. The purpose of this research was to investigate the strengths and limitations of the PRO instruments when analyzed free from developer construct and scoring recommendations to assess fit for purpose in various MM clinical trial populations. Methods: Data for the analysis included 3 MM RCTs (n=1,773) (Dimopoulos 2016, Palumbo 2016, Mateos 2018). The PRO analysis set consisted of 33 items from the EORTC QLQ-C30 and EQ-5D-5L collected at baseline and during the treatment phase of the RCTs. Item analysis and modern psychometric methods were applied to the PRO item pool as a 4-step process: (1) descriptive analysis of the items, (2) assessment of factor structure, (3) performance of factors across RCT populations (treatment naive, relapsed/refractory MM), and (4) assessment of meaningful change. Items were characterized using polychoric correlations to examine the inter-item association and relationships before determining appropriate factor structures. An exploratory factor analysis (EFA) followed by multidimensional item response theory (MIRT) and bifactor IRT models were conducted to determine how items fit into factors and to test a total symptom and total impact scoring option. Differential item functioning (DIF) was conducted to evaluation item and domain performance across study populations (treatment naïve vs. relapsed/refractory) and longitudinally (baseline vs. week 24). Meaningful change in these new domain constructs was evaluated using anchor-based techniques based on the EORTC-QLQ-C30 and EQ-5D-5L global items. A novel provisional latent class model approach creating responder groups was also developed and applied to assess meaningful change. Results: The 33 items from the EORTC QLQ-C30 and EQ-5D-5L demonstrated strong inter-item correlations supportive of pre-specified domain structures and consistent across RCT study populations. The EFA supported 3-domain structures for both symptoms and impacts separately. These domains were broadly consistent with the PRO instrument developer specifications but unique in several regards. These domains were statistically identical across RCTs. Model fit showed that a proposed bi-factor IRT (Symptom domain and Impact domain) fit better than the MIRT suggesting that subdomains are less useful than total domain scores. An extensive DIF analysis within this IRT framework found no evidence of substantial DIF effects. All evidence indicated that the items performed similarly across sample populations and time points. Anchor-based meaningful change calculations for the newly created total symptom score and the total impact score demonstrated separation between global health anchor groups but the meaningful change estimates were small. The latent class models demonstrated that treatment arms differed significant in responder rates within 1 RCT. Conclusions: The analyses confirmed psychometrically robust EORTC QLQ-C30 and EQ-5D-5L items in the MM population under newly specified factor structures. In addition, performance of the items allows for calculation of a total symptom score and total impacts score. The newly developed total domains performed identically across MM populations (treatment naïve versus relapsed/refractory). The results only focus on the on-treatment phase of the RCT so future research is needed to determine how psychometric methods can be adjusted to better accommodate survival status and censoring for progression in oncology RCTs. The psychometric properties and consistency of the findings across the newly created symptom and impact total domain structures support the results that daratumumab maintains HRQoL in patients with MM. Disclosures Gries: Janssen Research & Development, LLC: Employment. Fastenau:Janssen Research & Development, LLC: Employment. Iaconangelo:Janssen Research &Development, LLC: Consultancy. Serrano:Janssen Research & Development, LLC: Consultancy.

8042Background: ALCYONE, an ongoing multicenter, open-label, Phase 3 trial of subjects with newly diagnosed multiple myeloma not eligible for high-dose chemotherapy with stem cell transplantation d...

While atypical long-acting injectable antipsychotics (LAIs) offer the potential for increased adherence, access to medication poses challenges that may hinder their use. Janssen Connect * *Janssen Connect is a registered trade name of Janssen Scientific Affairs, LLC, Titusville, NJ, USA. (JC), a comprehensive information and assistance program, was designed to help patients who received a Janssen LAI initiate and maintain treatment after their health care professional (HCP) determined that the medication was the most clinically appropriate option. We conducted a formative and impact evaluation on early medication adherence of patients enrolled in JC and prescribed paliperidone palmitate.Using the program administrative files (December 2010-April 2014), 9354 patients whose HCP ordered paliperidone palmitate were included. Patient demographics, clinical characteristics, and request of JC program offerings were reported overall, and compared between patients requesting the injection center versus those who did not. Medication adherence based on the first 6 months of treatment while in the program and defined as achieving ≥80% proportion of days covered (PDC) was measured for patients receiving ≥2 paliperidone palmitate injections (n = 2659). Logistic models evaluated the association between requests for injection centers on medication adherence.Mean age of program enrollees was 40.6 (standard deviation = 13.9 years), 59.3% were men, and 42.5% were Medicare covered. While in the program, 79.9% did not experience a medication gap of ≥7 weeks and 87.0% achieved adherence. Injection center request was associated with medication adherence (adjusted odds ratio (aOR) ≤5 months: 0.03; 95% confidence interval (CI): 0.02-0.05; ≥6 months: aOR: 4.16; 95% CI: 2.72-6.36).The data sources used were designed for program implementation and not for research purposes.The high percentage of patients requesting injection center support and medication shipment in addition to other insurance-related program offerings signals the need for and value of a comprehensive support program for patients seeking LAI therapy. Providing patients with the option of alternative and more conveniently located injection centers may help them start and maintain their treatment.

The challenges of comparative effectiveness to support health technology assessment (HTA) agencies are important considerations in the choices of antipsychotic medications for the treatment of schizophrenia. Our aim was to assess the study methods used and outcomes reported in the published literature to address the question of comparative effectiveness of newer antipsychotic agents and the adequacy and availability of evidence to support HTA agencies. A systematic search of the PubMed database from 1 January 2009 to 30 September 2013 was conducted to identify studies evaluating new atypical antipsychotics reporting on comparative effectiveness. The systematic review comprised of studies on schizophrenia patients where at least two drugs were being compared and at least one treatment group received one of the following second-generation antipsychotics: risperidone, olanzapine, aripiprazole, paliperidone, asenapine, iloperidone, lurasidone, and quetiapine. The included studies were also required to have an efficacy, safety or economic outcome, such as Positive and Negative Syndrome Scale (PANSS) score, weight gain, resource utilization, or costs. Two reviewers (BW and GK) independently applied the inclusion criteria. Disagreements between reviewers were resolved by consensus, referring to the original sources. Information on the methodology and outcomes was collected for each included study. This included study description, head-to-head drug comparison, patient population, study methodology, statistical methods, reported outcomes, study support, and journal type. A total of 198 studies were identified from electronic search methods. The largest category of studies was randomized controlled trials [RCTs] (N = 73; 36.9 %), which were largely directed at the regulatory endpoint. Fewer studies were undertaken for HTA-purposes cohort studies (N = 53; 26.8 %), meta-analyses (N = 32; 16.2 %), economic studies (N = 14; 7.1 %), and cross-sectional studies (N = 13; 6.6 %). Direct head-to-head comparisons preferred by HTA were dominated by the comparison involving olanzapine and risperidone, representing 149 (75.3 %) and 119 (60.1 %) studies, respectively. RCTs, which are the primary study type for regulatory submissions, showed a lack of bias. Studies aimed at HTA were not as well performed. Cohort studies suffered from bias in the selection of comparison groups, lack of control for confounders, and differential dropout rates. As a group, cross-sectional studies scored poorly for bias, with a primary failure to identify a representative sample. Economic studies showed highly variable bias, with bias in the representation of effectiveness data, model assumptions without validation, and lack of sensitivity analyses. One limitation of this systematic review is that it only included studies from 2009 to 2013, potentially excluding some earlier comparator studies, particularly those involving first-generation antipsychotics. This review of comparative effectiveness studies of second-generation antipsychotic agents for schizophrenic patients revealed a wide range of study types, study methodologies, and outcomes. For traditional efficacy outcomes and select safety outcomes, there is strong evidence from many well-conducted studies; however, there are fewer studies of types preferred by HTA with limited head-to-head comparisons and a higher risk of bias in the execution of these studies.

Conduct a cost effectiveness analysis for the Paliperidone palmitate Research In Demonstrating Effectiveness (PRIDE) trial.PRIDE was a 15 month, prospective, randomized, open-label study in which once monthly paliperidone palmitate significantly delayed the time to first treatment failure (healthcare or criminal justice system [HC/CJS] events) versus oral antipsychotics in recently incarcerated adults with schizophrenia. The present analysis used a state government perspective and HC/CJS event data that were collected on a resource use questionnaire (RUQ) every 3 months.Since cost information was not collected in the trial, cost estimates from published literature and an analysis of multistate Medicaid data for CJS and HC events, respectively, were applied to RUQ event data. Effectiveness and costs were adjusted to 456 days (trial duration). Incremental cost effectiveness was calculated as the adjusted cost difference divided by the adjusted effectiveness difference.Adjusted costs (in US dollars) in the paliperidone palmitate group (n = 198) and the oral antipsychotic group (n = 193), respectively, were: non-drug costs $22,331 and $25,027; drug costs $18,592 and $7833; and total costs $40,923 and $32,860. Adjusted effectiveness differences and corresponding incremental cost effectiveness per event avoided (in parentheses) for paliperidone palmitate versus oral antipsychotics were as follows: 0.33 fewer CJS events ($24,409), 0.13 fewer psychiatric hospitalizations ($60,484), 0.46 fewer psychiatric hospitalizations or CJS events combined ($17,391), and 0.30 fewer incarcerations ($26,754).Costs for HC/CJS events avoided offset 25% of the greater drug cost for the paliperidone palmitate versus oral antipsychotic treatment group in this vulnerable population. Use of a recall-dependent RUQ for event rates and cost estimates instead of actual costs are potential limitations and may make the results conservative from a state government perspective. Indirect costs are likely to be substantial for this population, but were not considered in the analysis.

To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia.Preliminary data from an ongoing randomized, multicenter, 16-week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (or = 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion.Efficacy measures included: the proportion of patients with aor = 1 g/dL increase in hemoglobin by 4 weeks or aor = 2 g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL; and proportion of patients who never had a hemoglobin level within this range.A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 +/- 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred.Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.

Epoetin alfa (EPO) and darbepoetin alfa (DARB) are approved for the treatment of chemotherapy-related anemia (CRA) in patients with nonmyeloid malignancies. This study examined dosing and hematologic outcomes with these agents in community oncology clinics.Medical charts were abstracted retrospectively for 1005 patients (527 EPO, 478 DARB) with CRA (hemoglobin [Hb]or = 11 g/dL) who received EPO or DARB at 10 U.S. oncology clinics between January 2002 and March 2003.Outcome measures included dose and frequency of erythropoietic therapy, change in Hb at 4, 8, and 12 weeks after initiation of therapy, and transfusion of packed red blood cells.Baseline characteristics were generally similar between groups. Most EPO-treated patients received EPO once weekly, but 25% received EPO every 2-3 weeks, with 40,000 U the predominant dose. DARB was usually given every 1-2 weeks in doses ranging from 200-400 mcg/injection. Mean treatment duration was relatively short (8 weeks) in both groups, with a similar number of Hb determinations and similar incidence of red blood transfusion between groups. Hb increased from baseline in the EPO and DARB groups at 4 weeks (0.99 vs. 0.69 g/dL, p = 0.003), 8 weeks (1.39 vs. 1.06 g/dL, p = 0.011), and 12 weeks (1.43 vs. 1.11 g/dL, p = 0.055). Early Hb response (or = 1 g/dL increase by 4 weeks) was more common with EPO than DARB (48% vs. 38%, p = 0.008).EPO was superior to DARB for early hematologic outcomes in patients with CRA in community oncology clinics. Retrospective data collection and relative inexperience with DARB at the time of the study may limit the generalization of these results. Randomized, controlled trials comparing EPO and DARB are warranted.

To estimate a dose-conversion ratio (DCR) between epoetin alfa (EPO) and darbepoetin alfa (DARB) and compare the costs of both drugs at the estimated DCRs using average wholesale prices (AWPs).A search of PUBMED, CANCERLIT and references for papers and abstracts reporting on clinical trials of DARB or EPO for chemotherapy-related anaemia (CRA) identified 56 publications. A meta-analysis was conducted on the 12 eligible papers to estimate a DCR at which the two drugs were equally effective as measured by the area under the curve of haemoglobin (Hb) change (Hb AUC) at weeks 4 and 13. The DCR is based on the ratio of the coefficients of DARB and EPO doses in a regression of Hb AUC on those two variables, baseline Hb, Hb change calculation method, tumour type, and dosing frequency. Studies were frequency-weighted by the number of subjects. DCRs with confidence intervals (CIs) were calculated using a Monte-Carlo approach. Results from the regression were used to calculate DCRs for different dosing regimen comparisons - EPO three times weekly (TIW) versus DARB once weekly (QW), EPO TIW versus DARB once every 2 weeks (Q2W), EPO QW versus DARB QW, and EPO QW versus DARB Q2W. Relative cost effectiveness (RCE) was assessed by comparing drug costs at the estimated DCRs at $US 2003 AWPs [RCE = DCR . ($/U EPO)/($/mug DARB)].The regression results suggest an EPO QW : DARB QW DCR of 187 (95% CI 183, 191). Depending on the assumed starting dose, the DCR ranges from 126 to 137 for EPO TIW : DARB QW; from 128 to 139 for EPO TIW : DARB Q2W; and equals 191 for EPO QW : DARB Q2W. RCE was 2.0 for the main regression.The DCR of 330 : 1 estimated for the 2004 Hospital Outpatient Prospective Payment System by the Centers for Medicare and Medicaid Services is greater than the DCRs estimated based on Hb AUC. The DCR estimated in the primary regression suggests that based on AWPs, EPO is 2.0 times more cost effective than DARB.

Objectives: This study examined the burden of hospitalization of patients with Aspergillus and Candida infections in Australia from 1995 to 1999. Methods: Data were extracted from the National Hospital Morbidity Database. A hospitalization with an aspergillosis diagnosis was defined as any discharge with a diagnosis of aspergillosis. A hospitalization with a candidiasis diagnosis was defined as any discharge with a diagnosis of disseminated, invasive, or non-invasive candidiasis. Outcome measures included number of hospitalizations, length of stay (LOS), cost (AUS$), and mortality. Results: 4583 hospitalizations with an aspergillosis diagnosis and 57,758 hospitalizations with a candidiasis diagnosis were identified. These hospitalizations were associated with a total of 813,398 hospital days, AUS$563 million in cost, and 4967 in-hospital deaths during the study period. The mean LOS for a hospitalization with an aspergillosis diagnosis was 12 days, cost AUS$9,334, and was associated with 8% mortality. For disseminated, invasive, and non-invasive candidiasis, the respective mean LOS were 31, 17, and 12 days; costs were AUS$33,274, AUS$12,954, and AUS$7,694; and mortality was 26%, 9%, and 8%. Conclusions: Hospitalizations with diagnoses for fungal infections were associated with lengthy hospital stays, high costs, and high mortality.