Abstract: Graphical abstract [Formula: see text]

Abstract: BACKGROUND: Proteasome inhibitors (PIs) combined with an Rd backbone constitute commonly used regimens in RRMM in the US. Lack of data from head-to-head clinical trials comparing the efficacy of these PI-Rd triplets and the extent to which efficacy translates to benefit in routine care highlight the need for real-world evidence. We conducted a comparative effectiveness analysis of time to next therapy (TTNT) of these PI-Rd triplet combinations in a real-world representative cohort of RRMM patients. METHODS: In this retrospective cohort study, RRMM patients who initiated an index regimen with IRd, KRd, or VRd in ≥2nd line of therapy (LOT 2+) were followed between 1/2014-9/2018 in Optum's deidentified national electronic health records database. This database captures information on all patients treated by 〉 140,000 providers across 50 states in the US. It is representative of the US general population. Baseline data included: a modified frailty score utilizing age and Charlson Comorbidity Index1, ECOG performance status, CRAB symptoms, ISS stage, cytogenetic risk (high: del[17p], t[4;14] , or t[14;16]), history of: cardiovascular disease, peripheral neuropathy, stem-cell transplant, and uncontrolled hypertension, prior PI and/or IMID exposure and refractory status, time from diagnosis to start of index LOT, time from start of frontline therapy to start of LOT 2, and treatment-free interval prior to index LOT. Duration of therapy (DOT) and TTNT were estimated using Kaplan-Meier methods and compared using stratified (by LOT) ± baseline-adjusted Cox proportional hazard models with a repeated measures analysis of pt-LOTs with robust sandwich estimators to account for inclusion of patients in multiple LOTs. The main analysis was repeated in subgroups a priori defined by frailty score, cytogenetic risk, prior PI and/or IMID exposure and LOT. Observations were censored at time of loss to follow up/end of study period (9/30/2018). RESULTS: Overall, 650 patients with 733 pt-LOTs (IRd, n=168; KRd, n=208; VRd, n=357) were included; 20% of the RRMM patients in this cohort were treated at academic centers. In the I-/K-/V-Rd groups, respectively, median age was 71/65/71 years and 42/22/38% patients were ≥75 years old; 39/55/46% and 28/14/29% patients had a modified frailty score of intermediate and frail, respectively; 71/88/80% had a symptomatic relapse with at least 1 CRAB symptom; 20/28/13% patients had high cytogenetic risk; 69/72/90% patients were treated in 2-3 LOT, and 63/70/32% patients had prior exposure to a PI+IMID (P 〈 0.05 for all). The median follow-up was 14.4 months. Unadjusted median DOT of index LOT was 12.3/7.2/10.0 months, with a lower risk of discontinuation of the oral PI component for I in comparison to both K and V (HR[I vs K] of 0.66 and HR[I vs V] of 0.68) and R component in the IRd vs KRd and VRd groups (HR[I vs K] of 0.64 and HR[I vs V] of 0.75) (P 〈 0.05 for all). Unadjusted median TTNT was 12.7/8.6/14.2 months for I-/K-/V-Rd in LOT ≥2; with HR for TTNT of 0.76 (IRd vs KRd; P 〈 0.05); 1.01 (IRd vs VRd; P=0.96); 1.33 (KRd vs VRd; P 〈 0.05). The adjusted HRs for TTNT I-/K-/V-Rd in LOT ≥2 were 0.82 (IRd vs KRd); 0.93 (IRd vs VRd); 1.13 (KRd vs VRd; P 〉 0.05 for all), and were comparable between all 3 groups. A significant TTNT benefit for IRd vs KRd was observed among patients with high cytogenetic risk (HR: 0.47) and with intermediate frailtymodified score (HR: 0.60; P 〈 0.05 for all). CONCLUSIONS: In this real-world representative RRMM cohort, in unadjusted analyses, the IRd group had a longer DOT of the PI and R components and a longer TTNT in comparison with KRd. After adjusting for baseline confounders to separate the treatment effect, the I/K/V-Rd triplet combinations were comparable in TTNT, but IRd was significantly better than KRd in patients with high-risk cytogenetics and with an intermediate frailty score. Residual confounding is always a potential limitation of any non-randomized study. Conversely, the results of randomized, clinical trials are limited in generalizability as 40-60% of patients are excluded due to inability to meet eligibility criteria. This is especially pertinent in an elderly RRMM population as demonstrated in the real-world effectiveness results in this study. Ref: 1. Palumbo, et al. Blood. 2015;125:2068-2074 Figure Disclosures Chari: Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Oncoceutics: Research Funding; Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, 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; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Romanus:Takeda: Employment. Raju:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Other: Xcenda received funding from Takeda to complete this analyses., Research Funding; Xcenda, LLC: Employment. Cain:Takeda: Employment. Blazer:Xcenda: Employment; Takeda: Other: Xcenda received funding from Takeda for completion of this analysis, Research Funding. Farrelly:Xcenda: Employment; Takeda: Other: Xcenda received funding from Takeda for completion of this analysis, Research Funding. Stull:Takeda: Employment. Ailawadhi:Pharmacyclics: Research Funding; Cellectar: Research Funding; Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

Abstract: Background Multiple groups of pts, including elderly/frail pts and those with comorbidities, are typically under-represented in randomized controlled trials (RCTs). A recent study found an average of 16 eligibility criteria per cancer trial, 60% of which were related to comorbidity or performance status (PS; Unger, JNCI 2014). Phase 3 RCTs in MM have similar extensive eligibility criteria, resulting in populations that are not reflective of RW MM pts. Data from CONNECT-MM (Shah, CLML, 2017) and CoMMpass (Fiala, IMW 2017) suggest that 22-40% of RW pts are ineligible for MM RCTs, and an analysis of US RW relapsed/refractory MM (RRMM) pts showed that only 25-47% of pts would have been eligible for the phase 3 ASPIRE, TOURMALINE-MM1, ELOQUENT-2, and POLLUX studies, based on their differing eligibility criteria (Chari, EHA 2018). Further, data from CONNECT MM show that clinical trial ineligibility is associated with poorer long-term outcome (Shah, CLML, 2017). Thus, it is important to characterize RW MM pts and understand the discrepancies vs RCT populations. INSIGHT MM (NCT02761187) is the largest prospective, observational study in MM to date, following ~4,200 pts from 15 countries. Here we analyze RCT eligibility in INSIGHT MM pts, with a focus on the treatment of frail MM pts in the real world. Methods INSIGHT MM is following newly diagnosed (≤3 mos since treatment initiation) MM (NDMM) and RRMM (≤3 prior lines) pts. Demographics and disease characteristics, including medical history, comorbidities, PS, and frailty status (per IMWG Frailty Index criteria, Palumbo, JCO 2015), are collected using electronic case report forms at study baseline visit. For this analysis, pt data were reviewed vs 20 standard RCT eligibility criteria, using a conservative approach of classifying 'not available' data as 'eligible'; laboratory/PS and medical history exclusion criteria are summarized in the Table. Presence of hypertension was reviewed but omitted, as INSIGHT MM only collected data on 'hypertension requiring treatment' vs the standard RCT exclusion criterion of 'uncontrolled hypertension'. Results Data from 3,201 pts (1,761 NDMM, 1,440 RRMM) were analyzed. The proportions of pts who would be ineligible for RCTs based on each individual parameter, and the overall rate of ineligible pts, are shown in the Table. Overall, 39.2% of pts would have been ineligible for RCTs based on not meeting at least one of the 20 standard eligibility criteria included in this analysis, including 38.8% of NDMM and 39.7% of RRMM pts. The most common criteria excluding pts overall were another prior malignancy (7.5%), CrCl ≤30 mL/min (6.4%), cardiac arrhythmias (5.4%), platelets ≤75,000/mm3 (5.1%), and hemoglobin 〈 8.0 g/dL (4.8%). Common criteria were similar in NDMM and RRMM pts, except for higher rates of CrCl ≤30 mL/min (7.3%) and hemoglobin 〈 8.0 g/dL (5.9%) in NDMM pts, and higher rates of platelets ≤75,000/mm3 (7.4%) in RRMM pts. Frail pts are particularly likely to be ineligible for RCTs based on these standard criteria. Per study team evaluation applying the IMWG Frailty Index parameters, 320/1,685 evaluable pts (19%) were determined to be frail in INSIGHT MM. Of these 320 frail pts, applying the 20 standard eligibility criteria used in this analysis, 74.7% would have been ineligible for RCTs. Of 126 evaluable frail 1st line pts, 30 (24%) and 83 (66%) received doublet and triplet therapy, respectively, with median duration of treatment (DoT; Kaplan-Meier analysis) of 5.4 and 6.2 mos. Of 48 evaluable 2nd to 4th line pts, 26 (54%) and 21 (44%) received doublet and triplet therapy, respectively, with median DoT of 4.4 and 5.3 mos. Additional analyses of treatments received, reasons for treatment discontinuation, and DoT by frailty status and RCT eligibility will be presented. Conclusions A high proportion of INSIGHT MM pts (39.2%) were RCT-ineligible, consistent with or higher than previous reports. Common reasons for ineligibility included prior history of malignancy, low CrCl, and cardiac arrhythmias; more RRMM vs NDMM pts were excluded due to low platelet count. Analysis of frail pts suggests that these pts are particularly under-represented in RCTs using standard eligibility criteria. These findings emphasize the discrepancy between RW and RCT pt populations and the importance of RW data for evaluating effectiveness of treatment options. Initiatives are also ongoing to broaden oncology clinical trial eligibility criteria. Disclosures Hungria: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lee:Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Amgen: Consultancy, Research Funding. Abonour:Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy. Rifkin:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Terpos:Janssen: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria; Takeda: Honoraria, Other: Travel expenses, Research Funding; Celgene: Honoraria; Amgen: Honoraria, Research Funding. Leleu:Oncopeptide: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Sanofi: Honoraria; Takeda: Honoraria. Costello:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Takeda: Honoraria, Research Funding. van Rhee:Takeda: Consultancy; Sanofi Genzyme: Consultancy; EUSA: Consultancy; Castleman Disease Collaborative Network: Consultancy; Karyopharm Therapeutics: Consultancy; Kite Pharma: Consultancy; Adicet Bio: Consultancy. Weisel:Juno: Consultancy; Adaptive Biotech: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria. Puig:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; The Binding Site: Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Berdeja:AbbVie Inc, Amgen Inc, Acetylon Pharmaceuticals Inc, Bluebird Bio, Bristol-Myers Squibb Company, Celgene Corporation, Constellation Pharma, Curis Inc, Genentech, Glenmark Pharmaceuticals, Janssen Biotech Inc, Kesios Therapeutics, Lilly, Novartis, Poseida: Research Funding; Poseida: Research Funding; Amgen Inc, BioClinica, Celgene Corporation, CRISPR Therapeutics, Bristol-Myers Squibb Company, Janssen Biotech Inc, Karyopharm Therapeutics, Kite Pharma Inc, Prothena, Servier, Takeda Oncology: Consultancy. Cook:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Usmani:Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Pharmacyclics: Patents & Royalties, Research Funding; Takeda: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Amgen: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Celgene: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Array Biopharma: Patents & Royalties, Research Funding; Sanofi: Patents & Royalties, Research Funding, Speakers Bureau; Skyline DX: Consultancy. Thompson:GSK: Membership on an entity's Board of Directors or advisory committees; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; UpToDate: Patents & Royalties: Myeloma reviewer; Celgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Lynx Bio: Research Funding. Boccadoro:Mundipharma: Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria. Zonder:Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, 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; Intellia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caelum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Spencer:Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Specialised Therapeutics Australia: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Secura Bio: 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, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: 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, Research Funding, Speakers Bureau; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hajek:Janssen: Honoraria, Other: Consultant or advisory relationship, Research Funding; Amgen: Honoraria, Other: Consultant or advisory relationship, Research Funding; Celgene: Honoraria, Other: Consultant or advisory relationship, Research Funding; AbbVie: Other: Consultant or advisory relationship; Bristol-Myers Squibb: Honoraria, Other: Consultant or advisory relationship, Research Funding; Novartis: Other: Consultant or advisory relationship, Research Funding; PharmaMar: Honoraria, Other: Consultant or advisory relationship; Takeda: Honoraria, Other: Consultant or advisory relationship, Research Funding. Fanning:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Boyd:Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Armour:Millennium Pharmaceuticals: Other: Financial relationship; Janssen: Other: Financial relationship; Amgen: Other: Financial relationship; Celgene: Other: Financial relationship. Morgan:Myeloma Patients Europe, a non-profit organisation, which receives unrestricted grants from the following pharmaceutical companies: Amgen, Bristol Myers Squibb, Takeda, Janssen, Karyopharm, Novartis, Celgene and Sanofi.: Employment. Patel:Takeda: Employment. Carlson:Takeda: Employment. Ferrari:Takeda: Employment. Stull:Takeda: Employment. Ren:Takeda: Employment. Cherepanov:Takeda: Employment. Pottala:PPD, Inc., research organization contracted by Millennium Pharmaceuticals, Inc.: Employment. Chari:Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Oncoceutics: Research Funding; Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, 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; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy.

Abstract: Advances in novel agents and treatment combinations have improved prognosis and increased disease-free and overall survival for patients (pts) with multiple myeloma (MM). However, currently available data on disease presentation, treatment patterns, and outcomes for real-world MM pts at the global level are limited. This is due to several factors, including the overrepresentation of medically fit pts in clinical trials making generalization of outcomes challenging, the large number of treatment combinations, and varying global access/practice patterns. INSIGHT-MM (NCT02761187) is a global, prospective, non-interventional, observational study which aims to further understand disease and pt characteristics at presentation, treatment and clinical outcomes of real-world MM pts, as well as the association of treatment with tolerability, effectiveness, health-related quality of life (HRQoL), and healthcare resource utilization (HRU), on both a country-specific and global basis. As this is an observational study, no formal hypothesis will be tested. The INSIGHT-MM objectives are summarized in the Table. At least 5000 pts aged ≥18 yrs with newly diagnosed or relapsed/refractory MM will be enrolled over a 3-yr period and followed prospectively for ≥5 yrs, until death or end of study, whichever comes first. Pts not available for data collection for 〉 9 mos will have follow-up for survival. No study drug or medications will be provided; no modification of standard of care pt management will be assigned per protocol. Choice of therapy for all pts will be decided by the treating healthcare provider independent of study participation. Baseline pt and MM-specific characteristics, diagnosis, comorbidities, and prior therapies will be recorded based on review of hospital/clinic records. MM management, disease status and safety data will be obtained as part of routine office visits and recorded quarterly by each site in electronic case report forms. Quarterly assessment of MM management will be done based on prior and current treatment and recorded reason for treatment changes. Effectiveness of therapy will be assessed based on response, progression status, time to next therapy, vital status, and date and cause of death. Treatment tolerability will be assessed based on serious and non-serious adverse events leading to treatment discontinuation or dose modification. Incidence of second primary malignancies will be recorded. HRQoL, a specific type of patient reported outcome (PRO), will be collected at study entry and at predefined intervals following initiation of therapy using a secure electronic data collection system. HRQoL will be collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the MM module (EORTC QLQ-MY20). To capture pt satisfaction with MM-directed therapy, including the dimension of convenience, the 9-item Treatment Satisfaction Questionnaire for Medication will be used. The 5-dimension, 5-level EuroQol (EQ-5D-5L) PRO instrument will capture self-reported preference-based measures of health status suitable for calculating quality-adjusted life year (QALY) data to inform health economic evaluations. Frailty will be assessed using the Charlson Comorbidity Index, the Katz Index of Independence in Activities of Daily Living, and the Lawton Instrumental Activities of Daily Living. HRU will be evaluated using inpatient and intensive care unit admissions, length of stay, outpatient clinic visits, and emergency room visits. Data for all participating pts will be extracted by healthcare professionals at the site level and entered into a central database; descriptive statistical analyses will be done to address the study objectives. Interim analyses are planned after 1000 and 5000 pts have been enrolled and a final analysis will be conducted within 1 year after the last pt entered has completed ≥5 yrs follow-up. Data will be analyzed biannually to address emerging clinical questions identified by investigators to increase understanding of real-world treatment patterns. INSIGHT-MM aims to promote better understanding of contemporary demographics, patterns of care, and outcomes for real-world MM pts to inform treatment practice, supportive care, and pt outcomes. The study is currently ongoing and recruiting pts; further details regarding study rationale and protocol will be provided. Table 1 Table 1. Disclosures Davies: Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Zonder:Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Girnius:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Costello:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Usmani:Array: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Britsol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding. Omel:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Member of Takeda's "Patient Leadership Council". Token payment. Thompson:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: MDS/AML Registry; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AIM Specialty Health: Membership on an entity's Board of Directors or advisory committees; VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Multiple Myeloma International Registry; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Shah:Array: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schwartz:Bayer: Consultancy; Blue Cross and Blue Shield Associations: Consultancy; Pfizer: Consultancy; Takeda: Consultancy. Hajek:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terpos:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Hungria:Takeda: Consultancy; Roche: Consultancy; International Myeloma Foundation Latin America: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy; Amgen: Consultancy. Mateos:Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Cook:Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Leleu:Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; TEVA: Membership on an entity's Board of Directors or advisory committees. Goldschmidt:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, 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. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Pashos:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Romanus:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Cacioppo:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Bell:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Yu:Takeda Restricted Stock Unit (RSU), a publicly traded company: Equity Ownership; Takeda Development Center Americas, Inc., Deerfield, IL, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Luptakova:Takeda Oncology: Employment. Niculescu:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Noga:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Skacel:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Chari:Array Biopharma: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.