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1845 Closing the Efficacy and Effectiveness Gap: Outcomes in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated with Ixazomib-Lenalidomide-Dexamethasone (IRd) in Routine Clinical Practice Remain Comparable to the Outcomes Reported in the Phase 3 Tourmaline-MM1 Study

Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
multiple myeloma, Diseases, Therapies, Non-Biological, Plasma Cell Disorders, Lymphoid Malignancies
Saturday, December 7, 2019, 5:30 PM-7:30 PM
Hall B, Level 2 (Orange County Convention Center)

Roman Hajek, Prof, MD, PhD1, Jiri Minarik, MD, PhD2, Jan Straub, MD3*, Ludek Pour, MD4*, Alexandra Jungova5*, Jesus G. Berdeja, MD6, Mario Boccadoro, MD7, Lucie Brožová, MSc8*, Andrew Spencer, MBBS, FRACP, FRCPA, DM9, Frits van Rhee, MD, PhD10, Jorge Vela-Ojeda, MD, PhD11*, Michael A. Thompson, MD, PhD, FASCO12, Rafat Abonour, MD13,14, Ajai Chari, MD15, Gordon Cook, MB ChB, PhD, FRCP(Glas), FRCPath16*, Caitlin L. Costello, MD17, Faith E. Davies, MD18, Vania T.M. Hungria, MD, PhD19, Hans C. Lee, MD20, Xavier Leleu, MD, PhD21, Noemi Puig, MD, PhD22*, Robert M. Rifkin, MD23, Evangelos Terpos, MD, PhD24, Saad Z. Usmani, MD, FACP25, Katja C. Weisel, MD26*, Jeffrey A. Zonder, MD27, Magda Bařinová, MSc28*, Matyáš Kuhn, MSc29*, Jiri Silar, MSc30*, Lenka Capkova31*, Kenny Galvez, MD32*, Jin Lu, MD/Prof33, Tomas Skacel, MD34,35*, Jennifer Elliott34*, Brittany Demers, BS, BA36*, Dawn Marie Stull, Pharm.D., BCOP34*, Kaili Ren, PhD34* and Vladimir Maisnar, MD, PhD, MBA37*

1Department of Hemato-oncology, University Hospital Ostrava, and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
2Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, Olomouc, Czech Republic
3First Medical Department – Clinical Department of Hematology of the First Faculty of Medicine, General Teaching Hospital, Prague, Czech Republic
4Hematology, University Hospital, Brno, CZE
5Faculty Hospital Pilsen, Pilsen, Czech Republic
6Sarah Cannon Center For Blood Cancers, Nashville, TN
7Division of Hematology, University of Torino, Torino, Italy
8Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
9Department of Clinical Haematology, Alfred Health-Monash University, Melbourne, Australia
10Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR
11UMAE Especialidades Centro Medico La Raza IMSS, México, Mexico
12Aurora Cancer Care, Aurora Research Institute, Advocate Aurora Health, Milwaukee, WI
13IU School of Medicine, Indianapolis, IN
14Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN
15Icahn School of Medicine at Mount Sinai, New York, NY
16Department of Haematology, Clinical Trials Research Unit, NIHR (Leeds) IVD Cooperative, Leeds Teaching Hospital, Leeds, United Kingdom
17Department of Medicine, Division of Blood and Marrow Transplantation, Moores Cancer Center, University of California San Diego, La Jolla, CA
18Perlmutter Cancer Center, NYU Langone Health, New York, NY
19Department of Hematology, Clinica São Germano and Santa Casa Medical School, São Paulo, Brazil
20Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX
21Pôle Régional de Cancérologie, CHU de Poitiers, Poitiers, France
22Hospital Universitario de Salamanca Hematología. Instituto de investigación biomédica de Salamanca (IBSAL), Salamanca, Spain
23Hematology Research, US Oncology Research, Rocky Mountain Cancer Centers, Yampa Valley Medical Center, Texas
24Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
25Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, NC
26Department of Oncology, Hematology, Stem Cell Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
27Department of Malignant Hematology, Barbara Ann Karmanos Cancer Institute / Wayne State University School of Medicine, Detroit, MI
28Institute of Biostatistics and Analyses, Ltd, Brno, Czech Republic
29Institute of Biostatistics and Analyses, Ltd., Brno, Czech Republic
30Institute of Biostatistics and Analyses Ltd, Brno, Czech Republic
31Institute of biostatistics and analyses, Ltd., Brno, Czech Republic
32Hospital Pablo Tobón Uribe, Medellin, Colombia
33Peking University People's Hospital, National Clinical Research Center for Hematologic Disease, Beijing, China
34Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA
351st Department of Medicine, First Faculty of Medicine, Charles University and General Hospital in Prague, Prague, Czech Republic
36Oncology, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA
374th Department of Medicine - Haematology, Charles University Faculty Hospital, Hradec Králové, Czech Republic

Background

Ixazomib, the first oral proteasome inhibitor, has been approved for >3 years in >70 countries, for the treatment of RRMM pts who have received ≥1 prior therapy, on the basis of the TOURMALINE-MM1 study, which reported an overall response rate (ORR) of 78% and median progression free survival (PFS) of 20.6 mos. Although outcomes and tolerability in routine clinical practice often differ from data reported in clinical trials, growing evidence suggest that outcomes in patients treated with ixazomib-based regimens are comparable to those in the Phase 3 TOURMALINE-MM1 trial. We report on an expanded pooled analysis with longer follow-up of IRd therapy from the INSIGHT MM study (NCT02761187) and the Czech Registry of Monoclonal Gammopathies (RMG) to evaluate the effectiveness of IRd in RRMM pts in routine clinical practice.

Methods

INSIGHT MM is a large, prospective, observational study which has enrolled over 4,200 adult pts with MM from Europe (plus Israel, EUR), the US, Asia, and Latin America, with a planned follow-up of ≥5 years. The RMG comprises clinical data for >6,000 MM pts enrolled at 19 Czech and 4 Slovak centers. Eligible pts had 1–3 (INSIGHT) or ≥1 prior therapy (RMG) including an IR-based regimen. Individual pt level data on demographics, disease characteristics, treatment history, effectiveness, and safety from INSIGHT and RMG were integrated and analyzed. Best response or time to first response and PFS were determined as per investigator assessment, using IMWG criteria. PFS, duration of treatment (DOT), and overall survival (OS) were estimated using Kaplan Meier (KM) methodology, applying an exclusion criterion to account for immortal time bias (INSIGHT only).

Results

At data cutoff of 22 Nov 2018, 217 pts (83 in INSIGHT and 134 in RMG) from 11 countries had been included: 191 (88%) from EUR, 17 (8%) from the US, and 9 (4%) from Taiwan; 89% of pts were treated in an academic facility. At diagnosis, 32% of pts had ISS Stage III disease, 78% had bone lesions, 46% had anemia, and 12% had elevated creatinine. At study start, median age was 67 years with 12% >75 years; 58%/14% of pts had ECOG performance status 1/2. The distribution of immunoglobulin (Ig) heavy and light chain MM was as expected; 69% of pts had IgG MM. Overall, 21% of pts had extramedullary disease. Prior therapies included: bortezomib (90%), stem cell transplant (60%), thalidomide (47%), lenalidomide (26%), carfilzomib (8%), daratumumab (6%), and pomalidomide (2%).

Median time from diagnosis to start of IRd therapy was 42.1 mos; 43%/35%/22% of pts received IRd at 2nd/3rd/≥4th line. The most common reasons for starting IRd were relapse/progression (87%) and insufficient response (10%). The most common CRAB criteria present were bone lesions (48%) and anemia (18%). Median duration of follow-up was 12.6 mos in all pts. At data cutoff, 117 (54%) pts had discontinued IRd; median DOT was 11.9 (95% CI: 9.4–15.2) mos; at 12 mos, 49% (41.3–56.2) of pts were still on treatment (KM estimates).

Data on best response to therapy were available for 152 pts. The ORR was 74%, with 36% ≥VGPR; ORR with IRd at 2nd/3rd/ ≥4th-line therapy was 82%/71%/59%, including 43%/37%/17% ≥VGPR. Median time to first response was 1.2 mos (RMG); median time to best response was 3.7 mos (INSIGHT). Median PFS was 21.6 (95% CI: 13.6–26.7) mos across all lines. PFS rate at 12 mos was 62%, and 86 (40%) pts had progressed at data cutoff. Median time to next therapy (TTNT) was 31.5 (95% CI: 24.5–35.9) mos, with a 12-month rate of 74% across all lines. Overall, 60 (28%) pts received subsequent therapies including daratumumab (22%), pomalidomide (22%), bortezomib (20%), carfilzomib (17%), lenalidomide (15%), and thalidomide (12%). At data cutoff, 53 (24%) pts had died. Median OS was 36.7 (95% CI: 24.4–NR) mos, with 79% of pts alive at 12 mos (Figure). Regarding safety, ixazomib and lenalidomide dose reductions were required in 16% and 36% of pts, respectively, including 10% and 21% who required dose reductions due to AEs.

Conclusions

These findings show that the effectiveness of IRd in routine clinical practice (ORR 74%, median PFS 21.6 mos) is comparable to the efficacy of IRd reported in the registrational TOURMALINE MM1 trial (ORR 78%, median PFS 20.6 mos). IRd is well tolerated with no new safety signals, and low rates of dose reductions due to AEs for ixazomib (10%) and lenalidomide (21%). Outcomes should be interpreted with caution due to limited maturity of data.

Disclosures: 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. Minarik: Amgen, BMS, Janssen-Cilag, Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Straub: Amgen, Takeda, Celgene: Consultancy. Berdeja: Amgen Inc, BioClinica, Celgene Corporation, CRISPR Therapeutics, Bristol-Myers Squibb Company, Janssen Biotech Inc, Karyopharm Therapeutics, Kite Pharma Inc, Prothena, Servier, Takeda Oncology: Consultancy; 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. Boccadoro: AbbVie: Honoraria; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. van Rhee: Karyopharm Therapeutics: Consultancy; Kite Pharma: Consultancy; Adicet Bio: Consultancy; EUSA: Consultancy; Castleman Disease Collaborative Network: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy. Thompson: 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; Adaptive: Membership on an entity's Board of Directors or advisory committees; UpToDate: Patents & Royalties: Myeloma reviewer; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: 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; AbbVie: Research Funding; BMS: Research Funding; Lynx Bio: Research Funding. Abonour: BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Chari: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncoceutics: Research Funding; Pharmacyclics: 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. Cook: Karyopharm: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Costello: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Davies: Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor; Janssen, Celgene: Other: Research Grant, Research Funding. Hungria: Janssen: 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; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, 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; BMS: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lee: Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Amgen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy. Leleu: Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; GSK: Honoraria; AbbVie: Honoraria. Puig: Takeda: Consultancy, Honoraria; The Binding Site: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Terpos: Amgen: Honoraria, Research Funding; Celgene: Honoraria; Genesis: Honoraria, Other: Travel expenses, Research Funding; Janssen: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria; Takeda: Honoraria, Other: Travel expenses, Research Funding. Usmani: Bristol-Myers Squibb: Consultancy, Research Funding; Sanofi: Patents & Royalties, Research Funding, Speakers Bureau; Janssen: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Takeda: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Celgene: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Patents & Royalties, Research Funding; Amgen: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Array Biopharma: Patents & Royalties, Research Funding; Skyline DX: Consultancy. Weisel: Adaptive Biotech: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Research Funding; GSK: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Juno: Consultancy; Karyopharm: Other: IRC data review; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria. Zonder: 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; Amgen: 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; 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; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees. Skacel: Millennium Pharmaceuticals, Inc., subsidiary of Takeda Pharmaceutical Company Limited: Employment. Elliott: Takeda: Employment. Demers: Takeda: Employment. Stull: Takeda: Employment. Ren: Takeda: Employment. Maisnar: Janssen, Amgen, Celgene, Takeda, BMS: Consultancy, Honoraria.

*signifies non-member of ASH