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1918 Iberdomide (IBER) in Combination with Dexamethasone (DEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Anti-B-Cell Maturation Antigen (BCMA)-Exposed Cohort of the CC-220-MM-001 Trial

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Research, clinical trials, Plasma Cell Disorders, Clinical Research, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Sagar Lonial, MD1, Al-Ola Abdallah, MD2, Faiz Anwer, MD3, Ashraf Z. Badros, MD4, Manisha Bhutani, MD5, Abdullah Khan, MBBS, MSc6, Brea Lipe, MD7, Albert Oriol8*, Darrell White, MD9, Michael Amatangelo, PhD10*, Kexin Jin10*, Mark Masin10*, Vi Nguyen10*, Alpesh Amin10*, Paulo Maciag, MD PhD10* and Niels WCJ Van De Donk, MD11

1Winship Cancer Institute, Emory University, Atlanta, GA
2University of Kansas Medical Center, Kansas City, KS
3Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
4Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD
5Division of Plasma Cell Disorders, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC
6The James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center, Columbus, OH
7The Department of Medicine, University of Rochester Medical Center, Rochester, NY
8Catalan Institute of Oncology and Josep Carreras Institute, Hospital Germans Trias i Pujol, Badalona, AZ, Spain
9Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada
10Bristol Myers Squibb, Princeton, NJ
11Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, Netherlands, and Cancer Center Amsterdam, Amsterdam, Netherlands

Introduction: IBER, a novel, oral cereblon E3 ligase modulator (CELMoD®), has greater tumoricidal and immune-stimulatory effects compared with immunomodulatory drugs (IMiDs®), and has shown marked synergy with DEX and other antimyeloma therapies in preclinical models. IBER is being investigated in the phase 1/2 CC-220-MM-001 (NCT02773030) and phase 3 EXCALIBER-RRMM (NCT04975997) studies with different treatment combinations in patients (pts) with RRMM. In phase 1 of CC-220-MM-001, IBER + DEX showed notable efficacy (overall response rate [ORR] 31.9%) and a manageable safety profile. Given the emergence of novel anti-BCMA therapies in RRMM, assessment of pts with prior anti-BCMA exposure is an important consideration. Here we report results from the dose-expansion phase of IBER + DEX in heavily pretreated, triple-class-exposed (including ≥ 1 IMiD agent, ≥ 1 proteasome inhibitor [PI], and ≥ 1 anti-CD38 monoclonal antibody [mAb]) pts with RRMM who had also received prior anti-BCMA therapy.

Methods: Eligible pts had RRMM, had received ≥ 3 prior lines of therapy (including lenalidomide or pomalidomide, a PI, an anti-CD38 mAb, and an anti-BCMA therapy) and had documented progressive disease (PD) on or within 60 days of their last antimyeloma therapy (documented PD if chimeric antigen receptor [CAR] T cell therapy was the last therapy). IBER 1.6 mg was given orally on days 1–21 of each 28-day cycle, plus weekly DEX (40 mg; 20 mg if > 75 years of age). The primary objectives were to determine preliminary efficacy (ORR) and safety.

Results: As of April 15, 2022, 38 pts had received IBER + DEX in the anti-BCMA-exposed cohort. Median age was 65 (range 50–78) years and median time since initial diagnosis was 7.8 (0.6–24.8) years. High-risk cytogenetics were present in 31.6% of pts (52.6% pts were not evaluable), and 23.7% of pts had extramedullary plasmacytomas. Median number of prior regimens was 7 (4–15). All pts were triple-class exposed. Prior anti-BCMA therapies included CAR T cell therapy (36.8%), antibody-drug conjugates (34.2%), and T-cell engagers (TCEs; 23.7%) (Table); 78.9% of pts were refractory to the last antimyeloma regimen and 84.2% were triple-class refractory. Median follow-up was 8.1 (range 1.5–24.2) months, with a median number of 3.5 (1–19) cycles received and 21.1% of pts continuing treatment. Discontinuation was due mainly to PD, reported in 68.4% of pts.

ORR (≥ partial response) was 36.8%, with 2 (5.3%) complete responses, 5 (13.2%) very good partial responses, and 7 (18.4%) partial responses. Clinical benefit rate (≥ minimal response) was 39.5%. Responses were observed regardless of prior anti-BCMA therapy (Figure; updated data will be presented at the congress). Median duration of response was 7.5 (95% confidence interval [CI] 3.2–not reached) months, median progression-free survival was 2.4 (95% CI 2.1–4.2) months, and median time to response was 1.4 (range 0.9–5.4) months.

Grade (Gr) 3/4 treatment-emergent adverse events (TEAEs) occurred in 30 (78.9%) pts and were mostly hematologic; most frequent (≥ 20% pts) were neutropenia (50.0%, with 5.3% cases of febrile neutropenia), anemia (28.9%), leukopenia (23.7%), and thrombocytopenia (21.1%). Gr 3/4 infections occurred in 23.7% of pts and included pneumonia (21.1%); the occurrence of other Gr 3/4 non-hematologic TEAEs was low and included hypokalemia, hypertension, and mood alterations (all 5.3%). Two (5.3%) deaths were reported (due to sepsis and PD) which were not considered related to study treatment. IBER dose interruptions and reductions occurred in 24 (63.2%) and 7 (18.4%) pts, respectively. No pts discontinued IBER due to TEAEs.

Immunophenotyping showed comparable immunodeficiency (low absolute B-cell counts, T-cell counts, and CD4:CD8 ratio) between anti-BCMA-exposed pts and triple-class-exposed pts without prior anti-BCMA exposure; this was more pronounced following TCE-based therapies. Importantly, IBER + DEX remained immune-stimulatory in this population, increasing T- and NK-cell proliferation and T-cell activation.

Conclusions: IBER + DEX showed encouraging efficacy and safety in pts with triple-class-exposed RRMM and prior anti-BCMA therapy. The results are comparable to those from Cohort D of the same study, which is assessing IBER + DEX in pts with triple-class refractory RRMM. These findings support further development of IBER in RRMM, including in anti-BCMA-exposed pts.

Disclosures: Lonial: Novartis, BMS, GSK, Amgen, Merck, Janssen: Honoraria; AbbVie, Bluebird, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Novartis Pharma, and Takeda.: Consultancy; Celgene, Janssen, Takeda: Research Funding. Anwer: Allogene Therapeutics: Research Funding; BMS: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy. Badros: GSK, BMS: Research Funding; Amgen: Consultancy. Bhutani: Sanofi: Consultancy; Takeda: Research Funding; C4 Therapeutics: Research Funding; Avalo therapeutics: Research Funding; Millenium: Research Funding; Bluebird Bio: Research Funding; Celgene: Research Funding; BMS: Research Funding; Adaptive Biotechnologies: Research Funding; Celularity: Research Funding; Amgen: Research Funding; Legend BioTech: Research Funding; Janssen: Consultancy, Research Funding; MedImmune: Research Funding. Khan: Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Janssen: Honoraria; Secura Bio: Consultancy, Research Funding. Lipe: Harpoon: Research Funding; Amgen: Research Funding; Seagen Inc.: Research Funding; GSK: Consultancy; Sanofi: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Oriol: Sanofi: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Janssen: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. White: Amgen: Consultancy, Honoraria; Antengene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Forus: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Amatangelo: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company. Jin: Bristol Myers Squibb: Current Employment. Masin: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Nguyen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Amin: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Maciag: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Van De Donk: Servier: Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; 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; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding.

*signifies non-member of ASH