Global Treatment Standard in Multiple Myeloma Remains Elusive: Updated Results from the INSIGHT MM Global, Prospective, Observational Study

Introduction INSIGHT MM (NCT02761187) is the largest global, prospective, observational multiple myeloma (MM) study to date, with 4188 newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM) patients (pts) included in this cross-sectional analysis. The study aims to describe contemporary, real-world patterns of pt & disease characteristics, treatment patterns, & outcomes. An interim analysis of the first 1000 pts enrolled to INSIGHT MM suggested considerable regional variation in treatment patterns (Boccadoro et al, EHA 2018). The aim of the current analysis is to characterize treatment patterns by world regions & line of therapy (LOT) in the overall INSIGHT MM study population.

Methods Pts were enrolled at academic & community treatment facilities in 15 countries between July 2016 & July 2021. Data on prior & current treatments were collected at baseline & every 3 months. Full study methods have been reported previously (Costello 2019). We report a cross-sectional analysis of treatment regimens used in NDMM & RRMM pts at a data cut-off of Sept 30, 2021. A subset of pts with no protocol deviations (pts meeting all inclusion criteria who started index regimen <90 days before enrollment & enrolled at centers where data quality checks could be conducted) were included in an analysis of treatment shift patterns from first to second & subsequent LOTs.

Results Among the 4188 pts, there were 2338 (55.8%) NDMM & 1850 (44.2%) RRMM cases at enrollment. This includes 2046 pts from Europe (EUR; Belgium, France, Germany, Greece, Italy, Spain, Turkey, United Kingdom; also includes Israel); 1317 pts from the United States (US); 470 pts from Latin America (LA; Brazil, Columbia, Mexico); & 355 pts from Asia (China, Taiwan). Median follow-up was 27.9 months. In NDMM pts, triplet therapy was the most common frontline approach across all regions (71.1% of pts overall); only 12.0% of pts received frontline doublet therapy. Triplet therapy typically included a proteasome inhibitor (PI) & dexamethasone (d; 62.5%). The most commonly used regimen was bortezomib (V), lenalidomide (R), & d (VRd; 23.5%); V-based triplet therapy with d & an IMiD was prescribed to 34.7% of NDMM pts overall. V-based triplets were the most widely used regimens across all regions. The US was the only region where carfilzomib (K) was included in one of the three most frequently used regimens (KRd in 8.3% of pts). Choice of IMiD varied regionally: R was most commonly used in the US, & thalidomide in EUR, LA, & Asia. In EUR & LA, cyclophosphamide (alkylating agent) was more commonly used than IMiDs. Vd (4.1%) & Rd (4.0%) doublets were the fourth & fifth most common regimens overall.

Among RRMM pts, 49.6% received triplets & 33.7% received doublets. Triplet therapy was the most common approach across all LOTs & all regions except Asia; in Asia, doublets were more widely used than triplets (48.9% vs 42.4%). Rd was the most common regimen overall (15.4% across all regions & LOTs), & ixazomib-Rd (IRd) was the most common triplet (7.9% in all regions & LOTs; KRd was the second most common triplet overall [5.2%]). Unlike NDMM pts, RRMM pts were more likely to receive alternative PIs to V in ≥2nd LOT (IRd 6.8%; KRd 6.7%; VRd 2.7%), & daratumumab (D) was used instead of or alongside PIs in some triplets (DRd 4.9%; VDd 4.5%). Overall, 20.8% of pts received D as part of single-agent, doublet, triplet, or >triplet therapy. D was more widely used in the US (33.5%) than other regions (14.4-16.2%).

Treatment shift patterns were examined in 3263 pts for whom robust data were available (1236 who underwent stem cell transplantation [SCT] in first line of therapy & 2027 who did not [NSCT]). A shift from predominantly PI- or PI/IMiD-based frontline therapy in both SCT & NSCT pts to more varied second-line regimens, including monoclonal antibody (mAb) therapy, was observed (Figure). Treatment shift patterns in later LOTs & across regions will be presented.

Conclusions V-based triplets were the most common frontline treatment in NDMM pts in all regions. Regimens used in later LOTs in RRMM pts were more varied across regions, & generally included greater use of doublets, PIs other than V, & mAbs such as D. Acknowledging that treatment use is dependent on approval status & availability, this analysis shows that, while global frontline standard of care (SOC) is broadly established, there remains no consistent SOC in later LOTs; adoption of newer therapies, such as mAbs, varies across regions worldwide.

Puig:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored travel, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored travel, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored travel, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored travel, Research Funding; Sanofi: Consultancy, Honoraria; TBS: Honoraria, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees, Other: sponsored travel. Hungria:Takeda: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; GSK: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Davies:Takeda, Abbvie, Amgen, BMS/Celgene, Sanofi, GSK, Janssen: Membership on an entity's Board of Directors or advisory committees. Cook:Takeda, BMS, Amgen, Roche, Janssen, Sanofi, Karyopharm, Pfizer: Consultancy; Takeda, BMS: Research Funding; Takeda, BMS, Amgen, Janssen, Sanofi: Speakers Bureau. Hájek:Bristol Myers Squibb: Honoraria, Other: Consultant or advisory relationship, Research Funding; Novartis: Other: Consultant or advisory relationship, Research Funding; Celgene: Honoraria, Other: Consultant or advisory relationship, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant or advisory relationship, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant or advisory relationship, Research Funding; PharmaMar: Honoraria, Other: Consultant or advisory relationship; AbbVie: Honoraria, Other: Consultant or advisory relationship; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant or advisory relationship, Research Funding. Morgan:AstraZenca, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Karyopharm, Mundipharma, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Takeda, Gilead: Other: unrestricted core funding. Terpos:Novartis: Honoraria; Janssen: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Genesis: Honoraria, Research Funding; EUSA Pharma: Honoraria, Other: Travel expenses; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Other: Travel expenses, Research Funding; BMS: Honoraria. Thompson:Tempus Labs: Current Employment; Doximity: Current equity holder in publicly-traded company; AbbVie, Amgen, BMS, Denovo, Glaxo Smith Kline (GSK), Hoosier Research Network, Janssen, Lilly, LynxBio, Takeda, TG Therapeutics: Research Funding; Abbvie, Adaptive, Doximity, Elsevier Clinical Path (reviewer), Epizyme, Janssen, Sanofi, Takeda - Insight MM Registry, UpToDate (reviewer): Membership on an entity's Board of Directors or advisory committees. Usmani:Amgen, BMS, Janssen, Sanofi: Speakers Bureau; Abbvie, Amgen, BMS, Celgene, EdoPharma, Genentech, Gilead, GSK, Janssen,Oncopeptides, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, TeneoBio: Consultancy; Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, Takeda: Research Funding. Weisel:AstraZeneca: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria; Stemline: Honoraria; Roche: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; GSK: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Armour:Takeda, Janssen, Amgen, Novartis: Other. Ren:Takeda: Current Employment. Cherepanov:Takeda: Current Employment, Current equity holder in private company. Stull:Takeda: Current Employment. Berdeja:Sanofi: Consultancy, Research Funding; EMD Sorono: Research Funding; 2Seventy bio: Research Funding; Zentalis: Research Funding; Novartis: Research Funding; Legend Biotech: Consultancy; Janssen: Consultancy, Research Funding; Fate Therapeutics: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; Kite Pharma: Consultancy; Karyopharm: Research Funding; Teva: Research Funding; Acetylon: Research Funding; Celgene: Consultancy, Research Funding; Bluebird bio: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Cartesian Therapeutics: Research Funding; Takeda: Consultancy, Research Funding; SecuraBio: Consultancy; C4 Therapeutics: Research Funding; Amgen: Research Funding; Poseida: Research Funding; CARsgen: Research Funding; Incyte: Research Funding; Celularity: Research Funding; Ichnos Sciences: Research Funding; Lilly: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding.