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772 Belantamab Mafodotin, Bortezomib, and Dexamethasone Vs Daratumumab, Bortezomib, and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Overall Survival Analysis and Updated Efficacy Outcomes of the Phase 3 Dreamm-7 Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Refining the Evidence: Randomized Trials in Multiple Myeloma
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Monday, December 9, 2024: 11:15 AM

Vania Hungria, MD, PhD1, Pawel Robak, MD, PhD2*, Marek Hus, MD, PhD3*, Vera Zherebtsova, MD4*, Christopher Ward, MD, PhD5*, Phoebe Joy Ho, MBBS6, Roman Hajek, MD, PhD7, Kihyun Kim, MD8*, Sebastian Grosicki, MD, PhD9*, Hanlon Sia, MBBS FRACP FRCPA10*, Adam Bryant, MBBS(Hon), PhD, FRACP, FRCPA11*, Marcelo Pitombeira de Lacerda, MD, PhD12*, Gracia Aparecida Martinez, MD, PhD13*, Anna Maria Sureda Balarí, MD, PhD14, Irwindeep Sandhu, MD15, Claudio Cerchione, MD16, Peter Ganly, BMBCh, PhD17, Meletios Dimopoulos, MD18, Chengcheng Fu19*, Mamta Garg, MD20*, Al-Ola Abdallah, MD21, Moshe E Gatt, MD22, Albert Oriol, MD23*, Michele Cavo, MD24*, Robert Rifkin, MD, FACP25, Tomoaki Fujisaki, MD, PhD26*, Michał Mielnik, MD3*, Nick Pirooz, MHA27*, Joe Lee, PhD28*, Astrid McKeown, PhD29*, Rachel Rogers, MS27*, Hena Baig, BS30*, Lydia Eccersley, MBBS, MRCP, FRCPath, PhD28*, Sumita Roy-Ghanta, MD27* and Maria Victoria Mateos, MD, PhD31

1Clinica São Germano, São Paulo, Brazil
2Medical University of Lodz, Lodz, Poland
3Medical University of Lublin, Lublin, Poland
4Gorodskaya Klinicheskaya Bol’nitsa Im. S.p. Botkina, Moscow, Russian Federation
5Royal North Shore Hospital, Sydney, NSW, Australia
6Royal Prince Alfred Hospital, Camperdown, NSW, Australia
7University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic
8Sungkyunkwan University, Samsung Medical Center, Seoul, Korea, Republic of (South)
9Medical University of Silesia, Katowice, Poland
10Pindara Private Hospital, Gold Coast, Australia
11Liverpool Hospital, Sydney, Australia
12Universidade da Região de Joinville (Univille), Joinville, Santa Catarina, Brazil
13Hospital das Clínicas and Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil
14Institut Català d'Oncologia-L'Hospitalet L.-Barcelona, Barcelona, Spain
15Cross Cancer Institute, Edmonton, AB, Canada
16Hematology Unit, Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCS, Meldola (FC), Italy
17Christchurch Hospital, Christchurch, New Zealand
18National and Kapodistrian University of Athens, Athens, Greece
19The First Affiliated Hospital of Soochow University, Suzhou, China
20University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
21University of Kansas Cancer Center, Fairway, KS
22Department of Haematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
23Institut Català d’Oncologia and Josep Carreras Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain
24Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
25Rocky Mountain Cancer Centers - Denver – Midtown, Denver, CO
26Matsuyama Red Cross Hospital, Matsuyama, Japan
27GSK, Upper Providence, PA
28GSK, London, United Kingdom
29GSK, Stevenage, United Kingdom
30GSK, Mississauga, Ontario, CAN
31Hospital Universitario de Salamanca/IBSAL/CIC/Ciberonc, Salamanca, Spain

Patients with multiple myeloma (MM) are initially treated with triplet or quadruplet combination regimens that include proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies. However, most patients with MM experience progression after initial treatment and need efficacious subsequent-line combinations that incorporate new drug classes. Multiple studies in this relapsed/refractory MM population have shown progression-free survival (PFS) benefit; however, it is important that this translates into overall survival (OS) benefit for patients, as OS considers both efficacy and safety. Currently, daratumumab-containing regimens are widely used in this setting because triplet daratumumab combinations have shown significant PFS and OS benefits compared with their respective doublet backbones without daratumumab.

Belantamab mafodotin, a B-cell maturation antigen–targeting antibody-drug conjugate, has demonstrated single-agent sustained maintenance of deep and durable response with longer follow-up, owing to its multimodal mechanism of action that includes monomethyl auristatin F–induced cytotoxic cell death, antibody-dependent cellular cytotoxicity/phagocytosis, and immunogenic cell death. This has led to improvement in long-term clinical outcomes, including duration of response (DOR). Therefore, we anticipate that belantamab mafodotin in combination with standard-of-care therapies will show increasing OS benefit with longer follow-up.

DREAMM-7 (NCT04246047) is a global, 1:1 randomized, open-label, phase 3, head-to-head trial comparing the efficacy and safety of 2 triplets—belantamab mafodotin, bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd)—in patients with progression of MM after ≥1 prior line of therapy. The primary endpoint was independent review committee–assessed PFS. Secondary endpoints included OS, DOR, minimal residual disease (MRD) negativity, and time from randomization to disease progression after subsequent antimyeloma therapy or death from any cause (PFS2) (Hungria et al. N Engl J Med 2024).

In total, 494 patients were randomly assigned to receive BVd (n=243) or DVd (n=251). Baseline characteristics were balanced; overall, 51% of patients had received 1 previous line of therapy, 52% had exposure to lenalidomide, 34% had disease that was refractory to lenalidomide, and 28% had high-risk cytogenetic abnormalities. At a median follow-up of 28.2 months (range, 0.1-40.0 months), the primary endpoint was met, with a median PFS (95% CI) of 36.6 months (28.4 months-not reached [NR]) with BVd and 13.4 months (11.1-17.5 months) with DVd (hazard ratio [HR], 0.41; 95% CI, 0.31-0.53; P<.00001). BVd was associated with higher rates of complete response or better plus MRD negativity (25% vs 10%) and a more favorable restricted mean DOR (P<.001) than DVd. The median DOR (95% CI) was 35.6 months (30.5 months-NR) with BVd and 17.8 months (13.8-23.6 months) with DVd. Treatment benefits with BVd were also maintained after subsequent antimyeloma therapy, with an HR (95% CI) for median PFS2 of 0.56 (0.41-0.76). OS rates at 18 months with BVd vs DVd was 84% vs 73%, respectively. While median OS was NR in either arm at this first interim analysis, there was a strong trend in favor of BVd vs DVd, with an HR of 0.57 (95% CI, 0.40-0.80). Of note, in the CASTOR trial, median OS with DVd was 49.6 months in patients with a median of 2 prior lines of therapy.

We will present the results from the second planned interim analysis of DREAMM-7, with an approximate 3.3 years of follow-up; this will provide further insight on the potential survival benefit with BVd and include updates on response depth, DOR, MRD-negativity rates, and PFS2.

Overall, the DREAMM-7 head-to-head study of BVd vs DVd demonstrated statistically significant PFS benefit with BVd in patients with relapsed/refractory MM who have received ≥1 prior line of therapy. BVd also led to a deeper response and longer DOR than DVd. Since a strong and clinically meaningful early OS benefit with BVd was observed, updated practice-changing OS results are anticipated and will be presented at ASH 2024. Taken together, these results support BVd as a potential new standard of care in MM at first relapse or later.

Funding: GSK (Study # 207503)

Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Disclosures: Hungria: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer and Regeneron: Honoraria, Speakers Bureau; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hus: GSK: Honoraria; AbbVie: Honoraria; Johnson & Johnson - Janssen: Honoraria; AMGEN: Honoraria; Novartis: Honoraria; Bristol Myers Squibb - Celgene: Honoraria; Bristol Myers Squibb: Honoraria; MSD: Honoraria; Roche: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Eli Lily: Honoraria. Ward: International Society of Thrombosis and Haemostasis: Other: Education Chair; Drivetime Radio: Other: Moderators fees for podcast recording; Bayer: Honoraria, Speakers Bureau; Astra-Zeneca: Honoraria, Speakers Bureau. Ho: Novartis: Other: Research support on medical writing. Hajek: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. Sureda Balarí: Takeda, BMS/Celgene, MSD, Kite Gilead, Novartis, GenMab, Abbvie, Pierre Fabre, Autolus, Caribou, Incyte, Sanofi: Consultancy, Honoraria. Sandhu: Janssen, Celgene/BMS, Pfizer, Sanofi, GSK, Forus, Beigene: Consultancy; Janssen, Celgene/BMS, Pfizer, Sanofi, GSK, Forus, Beigene: Honoraria. Cerchione: GSK: Consultancy, Current holder of stock options in a privately-held company; Pfizer: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Menarini-Stemline: Consultancy; Curis: Consultancy; Skyline DX: Consultancy; Abbvie, AMGEN, Astellas, Beigene, BMS, Glycomimetics, GSK, Immunogen, Janssen, Jazz, Karyopharm, Menarini - Stemline, Oncopeptides, Pfizer, Sanofi, Servier, Stemline, Takeda: Other: Advisory board; Abbvie: Consultancy; AMGEN: Consultancy; Astellas: Consultancy; Beigene: Consultancy; Glycomimetics: Consultancy; BMS: Consultancy; Karyopharm: Consultancy; Jazz: Consultancy; Stemline: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy; GSK: Consultancy; Servier: Consultancy; Oncopeptides: Consultancy; Immunogen: Consultancy. Dimopoulos: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Swixx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Abbvie, Takeda, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Menarini: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; BeiGene Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee. Garg: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS Celgene: Membership on an entity's Board of Directors or advisory committees; CTI: Membership on an entity's Board of Directors or advisory committees; Janssen J&J: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Stemline: Membership on an entity's Board of Directors or advisory committees; AOP Pharma: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau. Gatt: Hadassah Medical Center Jerusalem: Current Employment. Rifkin: McKesson: Current Employment, Current equity holder in private company, Current equity holder in publicly-traded company; Amgen, BMS, Takeda, Fresenius-Kabi: Consultancy. Pirooz: GSK: Current Employment. Lee: GSK: Current Employment, Current holder of stock options in a privately-held company. McKeown: GSK: Current Employment, Current holder of stock options in a privately-held company. Rogers: GSK: Current Employment, Current holder of stock options in a privately-held company. Baig: GSK: Current Employment, Current holder of stock options in a privately-held company. Eccersley: GSK: Current Employment, Current holder of stock options in a privately-held company. Roy-Ghanta: GSK: Current Employment, Current holder of stock options in a privately-held company. Mateos: Amgen, Takeda, Regeneron: Honoraria; BMS/Celgene, Janssen-Cilag, Sanofi, Abbvie, Stemline, Oncopeptides, GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH