ALBERT

Description: Objective With the introduction of novel treatments for multiple myeloma, patients are now achieving deeper and sustainable clinical responses. Recent studies have demonstrated that achieving Minimal Residual Disease (MRD) negativity leads to better progression-free survival and overall survival outcomes (Lahuerta JJ, et al. J Clin Oncol 2017. 35[25]:2900-10; Munshi NC, et al. JAMA Oncol 2016. 3[1]:28-35; Landgren O, et al. Bone Marrow Transplant 2016. 51[12]:1565-1568). However, the relationship between MRD status and patient reported outcomes (PRO) has not been reported. The objective of this analysis is to evaluate whether PRO endpoints change by MRD status using data from two randomized clinical trials of daratumumab containing treatment regimens, POLLUX (Dimopoulos MA, et al. N Engl J Med 2016. 375[14]:1319-1331) and CASTOR (Palumbo A, et al. N Engl J Med 2016. 375[8]:754-766), for patients with relapsed or refractory multiple myeloma. Methods MRD status was assessed in POLLUX at the time of suspected CR, and at 3 and 6 months post-suspected CR for responders. Similarly, in CASTOR, MRD status was assessed for patients at the time of suspected CR and at 6 months and 12 months after first dose. MRD was assessed via next generation sequencing using the clonoSEQ® assay V2.0 (Adaptive Biotechnologies, Seattle, WA) at sensitivities of 0.001%. The PRO instruments (EORTC-QLQ-C30 and EQ-5D-5L) were collected in both POLLUX and CASTOR study prior to treatment, during the treatment phase, and post-progression. EQ-5D-5L assessed general health status and included an index value and visual analog scale (VAS) score. EORTC QLQ C30 assessed health related quality of life and included five functional scales (physical, role, emotional, social and cognitive), three symptom scales (fatigue, nausea & vomiting and pain) and a global health status (GHS) scale as well as six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Summary statistics (mean, standard deviation, median, min and max) by MRD status (baseline, prior to MRD negativity, MRD negativity prior to progression) were reported and for subjects who did not achieve MRD negativity (baseline, post baseline prior to progression) on a pooled sample of subjects from the two clinical trials. To interpret a meaningful change, a 5-point threshold was defined based on the EORTC guidelines for assessing quality of life in clinical trials. Results Overall 137 subjects in both CASTOR and POLLUX achieved MRD negativity and had PRO data available for analysis. At baseline, GHS, EQ-5D-5L VAS and index value were 62.1, 66.7, and 0.72 respectively (GHS and VAS scores closer to 100, and index value closer to 1.0 represent better health state). Mean values increased to 67.2, 70.9, and 0.75 after achieving MRD negativity. Pain scale (symptom scores closer to 0 represent less symptoms) reduced from 30.4 to 23.5 and fatigue was similar (33.8 at baseline to 31.2) when patients achieved MRD negativity. However, when we compared the five functional scales prior to and post MRD negativity, no evident differences were identified. The mean change from baseline to post-MRD-negativity in the EORTC QLQ-C30 GHS and Pain scores exceeded a 5-point threshold, reflecting a meaningful change in subject's health-related quality of life. A total of 893 subjects in the pooled data set did not achieve MRD negativity and had PRO data available for analysis (EQ-5D-5L data were not available for 3 subjects). Baseline values for these MRD positive subjects were 60.0, 65.3, and 0.71 and the mean post-baseline (pre-progression) values remained similar at 61.1, 66.0, and 0.71 for GHS, VAS, and the index value, respectively. Pain reduced from mean 33.3 to 29.4 and fatigue was similar, changing from 36.2 to 37.6. Conclusion To our knowledge, this is the first analysis exploring the relationship between MRD status and PRO endpoints. Results from this analysis demonstrate that patients who achieve MRD negativity status show a trend in better health-related quality of life, with meaningful improvement in EORTC QLQ-C30 GHS and pain scores. These preliminary findings indicate that overall health-related quality of life and symptom domains of EORTC-QLQ-C30 and EQ-5D-5L might be sensitive to changes in MRD status, with changes in GHS and Pain exceeding meaningful threshold for subjects. Disclosures Avet-Loiseau: Amgen: Consultancy, 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; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, 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; Abbvie: Membership on an entity's Board of Directors or advisory committees. He:Janssen global services: Employment. Gries:Janssen Research & Development, LLC: Employment. Pei:Janssen Research & Development, LLC: Employment. Saha:Janssen Research & Development, LLC: Employment. Chiu:Janssen Research & Development, LLC: Employment. Cote:Janssen Research & Development, LLC: Employment. Lam:Janssen Global Services, LLC: Employment.

Description: 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.

Description: 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.

Description: 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.

Description: 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.

Description: Introduction: DARA is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. In the phase 3 ALCYONE study (median follow-up of 40.1 months), DARA in combination with VMP (D-VMP) reduced the risk of disease progression or death by 58% versus VMP alone (median 36.4 vs 19.3 months; HR, 0.42; 95% CI, 0.34-0.51; P

Description: 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; P90% 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.