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5166 Long-Term Follow-up of Real-World Teclistamab Therapy for Relapsed/Refractory Multiple Myeloma from the IMWG Immunotherapy Working Group Committee

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster III
Hematology Disease Topics & Pathways:
Adult, Bispecific Antibody Therapy, Biological therapies, Treatment Considerations, Adverse Events, Study Population, Human
Monday, December 9, 2024, 6:00 PM-8:00 PM

Carlyn Rose Tan, MD1, Sireesha Asoori, MBBS, MPH2*, David Nemirovsky3*, Andriy Derkach, PhD3*, Larissa Brunaldi4*, Rakesh Popat5, Chris Lau5*, Efstathios Kastritis, MD6*, Joaquín Martínez-Lopez7*, Radhika Bansal, MBBS4*, Andre De Menezes Silva Corraes, MD4*, Saurabh Chhabra, MD8, Ricardo D. Parrondo, MD9, Sikander Ailawadhi10, Despina Fotiou, MD11*, Meletios Dimopoulos, MD11, Kwee Yong, MD, PhD5, Catriona Mactier, MD5*, Magdalena Corona7*, Adolfo Jesús Sáez Marín, MD7*, Hira Mian, MD12, Saad Z. Usmani, MD13, Brian G.M. Durie14, Thomas G. Martin, MD15 and Yi Lin, MD, PhD16

1Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
2University of California, San Francisco, CA
3Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
4Mayo Clinic Cancer Center, Rochester, MN
5Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
6Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Voula,Athens, AL, Greece
7University of Complutense, Hospital 12 de Octubre, Madrid, Spain
8Division of Hematology, Mayo Clinic, Phoenix, AZ
9Division of Hematology-Oncology, Mayo Clinic-Florida, Jacksonville, FL
10Division of Hematology, Mayo Clinic, Jacksonville, FL
11Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
12McMaster University, Hamilton, ON, Canada
13Myeloma Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
14International Myeloma Foundation, Studio City, CA
15University of California, San Francisco, San Francisco, CA
16Division of Hematology, Mayo Clinic, Rochester, MN

Introduction: Teclistamab (Tec) is the first approved BCMA x CD3 bispecific antibody for the treatment of triple-class-exposed patients with relapsed/refractory multiple myeloma (RRMM) based on the pivotal MajesTEC-1 study. Tec was associated with high overall response rate (ORR) of 63% in heavily pretreated patients. After a longer follow-up of 30.4 months, CR rate was 46.1%, median duration of response (DOR) was 24 months (95% CI, 17.0 – not estimable), and median progression-free survival (PFS) was 11.4 months (95% CI, 8.8 – 16.4). Herein, we present updated analysis of real-world outcomes and safety with tec in RRMM with extended follow-up of more than 12 months.

Methods: This is an international multicenter retrospective study of patients with RRMM treated with tec on-label at 9 academic centers from 5 countries (United States, United Kingdom, Greece, Spain, and Canada) through the International Myeloma Working Group (IMWG) Immunotherapy Committee. Patients with RRMM treated with commercial tec at the respective institutions between May 24, 2022 to January 4, 2024 were included. Median follow-up was 14 months with data collected until July 15, 2024. High-risk cytogenetic abnormalities (HRCA) was defined as 1q+, t(4;14), t(14;16), t(14;20), and/or del(17p). Response was assessed using the IMWG consensus criteria. Patient characteristics were summarized by frequency (percentage) or median (interquartile range [IQR] or range). PFS, overall survival (OS), DOR were evaluated using the Kaplan-Meier method.

Results: There were 223 patients included in this analysis with the following characteristics: median age of 67 (range 33-91) with 24% ≥75 years; 45% female; 74% White, 10% Black, 9% Asian, and 7% other/unknown; 86 of 176 (49%) with high risk cytogenetics, including del(17p), t(4;14), t(14;16), t(14;20), and gain/amp 1q; 29.4% (37/126) with known extramedullary disease; 14% with creatinine clearance ≤30 ml/min. Patients received a median of 6 (IQR, 4-8) prior lines of therapy with 52% (107/206) being penta-drug refractory. Among 212 patients with available data, 161 (75.9%) patients would have been ineligible for MajesTEC-1. There were 94 (42%) patients who received prior BCMA-directed therapy (29.8% antibody-drug conjugate [ADC] alone; 45.7% CART alone; 6.3% bispecific antibody alone; 17.0% ADC and CART). Median time from diagnosis to tec initiation was 6.1 (range 0.6-29.2) years.

For the 206 response-evaluable patients, ORR was 66%, including 25.2% ≥CR, 33.5% VGPR, and 7.3% PR. ORR for the 90 response-evaluable patients with prior BCMA-directed therapy was 54.5% (21.1% ≥CR, 26.7% VGPR, 6.7% PR). After a median follow-up of 14 (95%CI, 13-14) months, median PFS and OS were 8.8 (95% CI, 5.5-14) and 20 (95% CI, 18-not reached [NR]) months, respectively. 12-month PFS estimate was 46% (95% CI, 40%-54%), and 12-month OS rate was 65% (95% CI, 59%-72%). Median DOR was 17 (95% CI, 17-NR) months with 12-month estimate of 68% (95% CI, 60%-77%).

Tec step-up dosing occurred in the outpatient setting for 57 (25.6%) patients. CRS occurred in 119 out of 222 (53.6%) patients with almost all being grade 1-2, except for 1 grade 4 event. ICANS occurred in 18 out of 216 (8.3%) patients (grade 1-2: 5.1%; grade 3-4: 2.8%). Any grade infection occurred in 130 (58.3%) patients; 25.1% of patients had grade ≥3 infection, including 10 patients with grade 5 infection. While receiving teclistamab, 79 (35.4%) patients had ≥2 infections. IVIG was given in 114 out of 164 (69.5%) patients.

Conclusion: In this multicenter international real-world analysis of outcomes and safety associated with tec, ORR was high at 66% with 25.2% of patients achieving ≥CR. CR rates may be underestimated due to infrequent bone marrow confirmation in the real-world datasets. Encouragingly, ORR was 54.5% in BCMA exposed RRMM patients, including 21.1% with ≥CR. After a median follow-up of 14 months, heavily pretreated patients including patients with prior BCMA therapy had durable responses with median PFS of 8.8 months and median DOR of 17 months. There were no new safety signals noted in this real-world study. This is the largest real-world study to date of teclistamab with long-term follow-up of more than 12 months. Additional data including more patients, longer follow-up and results from difficult to treat subgroups will be presented at the meeting.

Disclosures: Tan: Takeda: Research Funding; Sanofi: Honoraria; Janssen: Honoraria, Research Funding. Popat: BMS: Honoraria; Regeneron: Other: IDMC member; GSK: Honoraria, Research Funding; J&J: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria, Research Funding; Roche: Honoraria; Sanofi: Honoraria. Kastritis: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genesis Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, 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; Amgen: Honoraria. Martínez-Lopez: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Incity: Research Funding. Bansal: Kite Pharma: Other: Travel Support. Chhabra: Omeros: Speakers Bureau; Bristol Myers Squibb, Amgen, Janssen, Novartis, Syndax, Ionis, Sanofi, and GlaxoSmithKline: Research Funding; GlaxoSmithKline, Sanofi: Honoraria. Parrondo: AstraZeneca: Honoraria; Sanofi Aventis: Honoraria; Bristol Myers Squibb, GSK: Research Funding. Ailawadhi: BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Ascentage: Research Funding; Abbvie: Research Funding; Xencor: Research Funding; Cellectar: Consultancy, Honoraria, Research Funding; Johnson and Johnson: Consultancy, Research Funding; Regeneron: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Sanofi: Consultancy; Amgen: Consultancy, Research Funding; Takeda: Consultancy; Beigene: Consultancy; Pharmacuclics: Consultancy, Research Funding. Fotiou: Sanofi: Honoraria; Janssen: Honoraria. Dimopoulos: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; 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; Menarini: 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; BeiGene Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; 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; 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. Mian: BMS: 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; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria. Usmani: Sanofi: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Gilead: Research Funding; Array Biopharma: Research Funding; Oncopeptides: Consultancy; SkylineDX: Consultancy, Research Funding; Gracell: Consultancy; Johnson & Johnson - Janssen: Consultancy, Research Funding; SeaGen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb - Celgene:: Consultancy, Research Funding; Genentech: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy, Research Funding; Bristol-Myers Squibb - Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Pharmacyclics: Research Funding; Merck: Research Funding; SecuraBio: Consultancy; Takeda: Consultancy, Research Funding; TeneoBio: Consultancy. Martin: Sanofi: Research Funding; BMS: Research Funding; GSK, Pfizer, Roche: Honoraria; Janssen: Research Funding; Poseida: Research Funding. Lin: Legend: Consultancy; Regeneron: Consultancy; NexImmune: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Sanofi: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding.

*signifies non-member of ASH