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

Introduction In addition to efficacy and safety, novel regimens for the treatment of multiple myeloma (MM) should be assessed in terms of disease-related symptoms, the adverse events patient's experience, and their effect on health-related quality of life (HRQOL). Patient-reported outcome (PRO) measures capture these experiences from the patient's perspective. However, an interpretative challenge of PROs is understanding the magnitude of change that can be considered clinically meaningful. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, supplemented with the multiple myeloma-specific module (QLQ-MY20), are commonly used PRO measures in MM trials. However, the minimally important difference (MID) in QLQ-MY20 scores, between groups or for an individual who may be categorized as a responder, has not been established. Previously, estimates based on the statistical variability of scores, or a universal 10-point threshold, have been applied to approximate an MID or responder definition (RD). This study aims to provide empirical estimates of the MID and RD for the QLQ-MY20 in an adult newly diagnosed (ND) and relapsed/refractory (RR) MM population using clinical trial data and qualitative patient interviews. Methods Data were pooled from three completed Phase III clinical trials assessing the efficacy and safety of carfilzomib-containing regimens in patients with RRMM (ASPIRE [NCT01080391], ENDEAVOR [NCT01568866]) or NDMM (CLARION [NCT01818752]). A recommended MID or RD should come from triangulating estimates from several different techniques. MIDs were estimated quantitatively by evaluating the mean PRO score changes in patients grouped as 'improved', 'stable' or 'deteriorated' according to external anchors. The anchors were selected based on variables common to the source datasets expected to reflect changes in PRO scores, and assessed for suitability through correlations. Those included were based on a PRO measuring chemotherapy-induced neuropathy (FACT/GOG-Ntx), ECOG performance status, and matched CTCAE toxicity events. RDs for deteriorations and improvements in health were estimated using the same anchor measures through receiver operating characteristic (ROC) curves, supported by 'distribution-based' estimates incorporating the statistical variability of scores. Qualitative telephone interviews were conducted to obtain patient insights from patients with MM regarding what constitutes meaningful change, to further support RD estimates and triangulate quantitative findings. This directly utilizes patient input to define an important treatment benefit and translate HRQOL change scores into tangible and clinically relevant impacts of the treatment on a patient. Interview participants were independent to the clinical trial samples and recruited via patient associations and clinical sites in the US and UK. Ethical approval was obtained for the study. Results The pooled sample from the clinical trials comprised 2,147 patients for analysis; 14 additional patients (to date) were interviewed. MID and RD estimates varied as a result of the different methods, anchors and time points used to derive them. Based on the clinical trial sample, the range of MID and RD estimates for the QLQ-MY20 subscales were calculated and are presented in Table 1. The qualitative interview findings to date suggest that patients consistently understood the subscale concepts, relevance and response options for each domain of the QLQ-MY20. Patients discussed the concept of meaningful change at the domain level and provided reliable meaningful change estimates. The quantitative and qualitative findings will be triangulated to derive weighted estimates recommended for use in future studies. A single global estimate may not be appropriate for all subscales, in which case a range may be recommended. Conclusions Updated data based on full triangulation of the qualitative and quantitative evidence will be presented at the annual meeting. Findings from the current study will inform the development of new recommended interpretation guidelines for QLQ-MY20. These values will facilitate power analysis when designing studies and enable consistent interpretation of treatment effect on patients' HRQOL by regulators, payers and clinicians. Disclosures Yucel: Amgen: Employment, Equity Ownership. Trigg:Adelphi Values: Employment; Amgen: Consultancy. Sully:Adelphi Values Ltd: Employment; Amgen: Consultancy. Harper:Adelphi Values: Employment; Amgen: Consultancy. Bonner:Amgen: Consultancy; Adelphi Values: Employment. Shah:Nkarta: Consultancy; Amgen: Consultancy; Sutro Biopharma: Research Funding; University of California San Francisco: Employment; Indapta Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy; Bluebird: Research Funding; Janssen: Research Funding; Kite: Consultancy; Nekktar: Consultancy; Teneobio: Consultancy; Celgene: Research Funding; Indapta Therapeutics: Equity Ownership; Sanofi: Consultancy; Takeda: Consultancy. Panjabi:Amgen: Employment, Equity Ownership. Cocks:Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Endomag Ltd.: Consultancy; Adelphi Values: Employment.