-Author name in bold denotes the presenting author
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3385 Long-Term Efficacy and Safety of Elranatamab Monotherapy in the Phase 2 Magnetismm-3 Trial in Relapsed or Refractory Multiple Myeloma (RRMM)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Research, Bispecific Antibody Therapy, Clinical Research, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Michael Tomasson, MD1*, Shinsuke Iida2, Ruben Niesvizky, MD3, Mohamad Mohty, MD, PhD4, Nizar J Bahlis, MD5, Joaquin Martinez-Lopez, MD, PhD6*, Guenther Koehne, MD, PhD7, Paula Rodriguez Otero, MD, PhD8*, H. Miles Prince, MD9, Andrea Viqueira, MD10*, Eric Leip11*, Umberto Conte, PharmD12*, Sharon T Sullivan11* and Alexander Lesokhin, MD13,14

1University of Iowa, Iowa City, IA
2Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
3Division of Hematology & Medical Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY
4Saint-Antoine Hospital, Sorbonne University, Paris, France
5Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada
6Hospital Universitario 12 de Octubre, CIBER-ONC CB16/12/00369, CNIO, Madrid, Spain
7Baptist Health South Florida, Miami Cancer Institute, Miami, FL
8Cancer Center Clínica Universidad de Navarra (CCUN), CIMA, CIBERONC, IDISNA, Pamplona, Spain
9Epworth Freemasons, Melbourne VIC, Australia
10Pfizer SLU, 28108, Madrid, ESP
11Pfizer, Cambridge, MA
12Pfizer, New York, NY
13Weill Cornell Medicine, New York, NY
14Division of Hematology and Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

BACKGROUND

Elranatamab is a humanized, bispecific antibody that targets B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells, with the aim of inducing T-cell–mediated cytolysis of the myeloma cells. In the MagnetisMM-3 (NCT04649359) trial, an open-label, multicenter, non-randomized, phase 2 registrational study of elranatamab monotherapy, patients with RRMM who had not received prior BCMA-directed therapy (ie, BCMA-naïve patients; n=123) achieved objective responses with an overall response rate (ORR) of 61%. Here, we report the long-term efficacy and safety of elranatamab.

METHODS

Eligible patients had previously received at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody. Patients received step-up doses of 12 and 32 mg elranatamab subcutaneously on days 1 and 4 of cycle 1, respectively, followed by 76 mg elranatamab once-weekly (QW), starting on day 8 of the first 4-week cycle. Patients who received ≥6 months of QW dosing and achieved ≥ partial response lasting at least 2 months were transitioned to a once every 2 weeks (Q2W) dosing schedule and from Q2W to once every 4 weeks after at least 6 Q2W cycles. Treatment with elranatamab continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was ORR, assessed by blinded-central review per International Myeloma Working Group criteria. Minimal residual disease (MRD) status was assessed using next-generation sequencing, with MRD negativity defined as <1 myeloma cell in 105 nucleated cells. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) severity were graded by American Society for Transplantation and Cellular Therapy criteria.

RESULTS

After a median follow-up of 15.9 months (data cutoff, April 16, 2023), 32.5% of patients remained on treatment. The confirmed ORR was 61.0% (n=123; 95% CI, 51.8-69.6), with 35.8% of patients achieving complete responses (CR) or better. Among evaluable patients (those with ≥CR and evaluable for MRD, n=29), 89.7% achieved MRD negativity. Median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) have not been reached, and the probabilities of maintaining a response, being progression-free, and being alive at 15 months were 70.8% (95% CI, 58.2-80.2), 50.2% (95% CI, 40.2-59.3), and 56.3% (95% CI, 47.0-64.6), respectively. All participants (100%) had ≥1 any grade treatment-emergent adverse events (TEAEs), and 70.7% of patients had grade 3/4 TEAEs. The most common any grade (≥25%) and grade 3/4 (≥10%) adverse events (any grade, grade 3/4) were infections (69.9%, 40.7%), CRS (57.7%, 0%), anemia (48.8%, 37.4%), neutropenia (48.8%, 48.8%), diarrhea (41.5%, 1.6%) thrombocytopenia (31.7%, 23.6%), lymphopenia (26.8%, 25.2%), fatigue (36.6%, 4.1%), nausea (26.8%, 0%), injection site reaction (26.8%, 0%), hypokalemia (26.0%, 10.6%), cough (26.0%, 0%) pyrexia (30.9%, 4.1%), decreased appetite (33.3%, 0.8%), leukopenia (15.4%, 13.0%) and COVID-19 pneumonia (14.6%, 11.4%).

CONCLUSIONS

Extended follow-up from the ongoing phase 2 MagnetisMM-3 trial of elranatamab in heavily pretreated participants with RRMM demonstrated sustained clinical efficacy, with median DOR, PFS, and OS not reached, and no new safety signals.

Disclosures: Iida: Ono: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Amgen: Research Funding; GlaxoSmithKlein: Consultancy, Research Funding; Alexion: Research Funding; Pfizer: Consultancy, Research Funding; Shionogi: Research Funding; Otsuka: Consultancy; Regeneron: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Scuibb: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Research Funding; Chugai: Research Funding; Novartis: Consultancy, Research Funding; Otsuka: Research Funding. Niesvizky: BMS/Celgene: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria, Research Funding. Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding. Bahlis: Karyopharm therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Honoraria; BMS: Consultancy, Honoraria; GSK: Consultancy, Other: member of steering committee; Forus: Consultancy, Honoraria; Takeda: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Other: member of steering committee; Amgen: Consultancy, 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, Research Funding; Pfizer: Consultancy, 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, Other: IRC member and chair, Research Funding. Rodriguez Otero: Amgen: Other: Honoraria for lectures; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Regeneron: Other: Honoraria for lectures; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Roche: Consultancy. Prince: Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Viqueira: Pfizer: Current Employment, Current holder of stock options in a privately-held company. Leip: Pfizer: Current Employment. Conte: Pfizer: Current Employment, Current holder of stock options in a privately-held company. Sullivan: Pfizer: Current Employment, Current holder of stock options in a privately-held company. Lesokhin: Janssen: Research Funding; BMS: Research Funding; Genentech: Research Funding; Serametrix (now Caprion): Patents & Royalties; Iteos: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Arcellx: Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure: Elranatamab is an investigational BCMA-CD3 bispecific antibody for the treatment of multiple myeloma

*signifies non-member of ASH