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897 Outcomes of Teclistamab (Tec) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) with Prior Exposure to BCMA-Directed Therapy (BCMA-DT): A Multicenter Study from the U.S. Multiple Myeloma Immunotherapy Consortium

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Exploring T Cell Redirecting Therapies, Mutation Profiles and Early Relapse
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Diseases, Real-world evidence, Lymphoid Malignancies
Monday, December 9, 2024: 3:15 PM

Danai Dima, MD1, Mariola A Vazquez-Martinez, MD2, James A Davis, PharmD3*, Utkarsh Goel, MBBS1, Aimaz Afrough4*, Aishwarya Sannareddy, MBBS4*, Oren Pasvolsky, MD5, Beatrice Razzo, MD6, Rahul Banerjee, MD, FACP7, Jack Khouri, MD1, Ariel Grajales-Cruz2*, Alex Lieberman-Cribbin8*, Masooma Shifa Rana9*, Kelley Julian, PharmD10*, Shaun DeJarnette11*, Andrew J Portuguese, MD7, Mahmoud R. Gaballa, MD5, Gabriel De Avila2*, Sandra Susanibar-Adaniya, MD6, Shahzad Raza, MD1, Megan M Herr, PhD12, Evguenia Ouchveridze, MD11, Tiffany Richards, PhD, NP5, Hitomi Hosoya, MD, PhD9, Lekha Mikkilineni, MD, MA9, Gurbakhash Kaur, MD, MA13, Daniel Schrum, PharmD14*, Omar Castaneda, MD15, Adriana Rossi, MD, MSc16, Chenyu Lin, MD14, Peter A. Forsberg, MD17, Yi Lin, MD, PhD18, Shebli Atrash, MD19, Douglas W Sborov, MD10, Kenneth H. Shain, MD, PhD2, Peter M. Voorhees, MD19, Shambavi Richard, MD16, Alfred L. Garfall, MD6, Doris K. Hansen, MD2, Surbhi Sidana, MD9, Krina K. Patel, MD, MSc5, Andrew J. Cowan, MD7, Larry D Anderson Jr., MD, PhD20, Hans C. Lee, MD5, Faiz Anwer, MD1, Christopher Ferreri, MD19 and Leyla O. Shune, MD11

1Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
2H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
3Medical University of South Carolina Hollings Cancer Center, Charleston, SC
4UT Southwestern Simmons Cancer Center, Dallas, TX
5The University of Texas MD Anderson Cancer Center, Houston, TX
6University of Pennsylvania Abramson Cancer Center, Philadelphia, PA
7University of Washington Fred Hutchinson Cancer Center, Seattle, WA
8Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
9Stanford University, Stanford, CA
10University of Utah Huntsman Cancer Institute, Salt Lake City, UT
11University of Kansas Medical Center, Kansas City, KS
12Roswell Park Comprehensive Cancer Center, Buffalo, NY
13Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX
14Duke University Cancer Institute, Durham, NC
15Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
16Icahn School of Medicine at Mount Sinai Tisch Cancer Institute, New York, NY
17University of Colorado Cancer Center, Aurora, CO
18Division of Hematology, Mayo Clinic, Rochester, MN
19Atrium Health Levine Cancer Institute, Charlotte, NC
20Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX

Background: Tec is a BCMA-directed bispecific antibody (BsAb) approved for RRMM after ≥4 prior lines of therapy (LOT) based on the MajesTEC-1 trial. However, patients who had previously received a BCMA-DT were excluded from MajesTEC-1. Herein, we evaluated outcomes of RRMM patients with prior exposure to BCMA-DT treated with standard-of-care Tec.

Methods: This was a multicenter retrospective cohort study. We compared variables between different groups using Chi-squared and Kruskal-Wallis tests, and assessed progression free survival (PFS) and overall survival (OS) using Kaplan Meier and Cox proportional hazards model. We used the maximally selected rank statistics method to determine the optimal cut-off point for continuous variables to find the most significant difference in PFS among different groups.

Results: A total of 385 patients were included in this study. 193 patients had received a prior BCMA-DT, of whom 77%, 22%, and 1% had received 1, 2, and 3 prior anti-BCMA agents, respectively. In patients who had received a prior BCMA-DT, 35% were aged ≥70 years, 24% had ECOG performance status (PS) ≥2, 61% had high-risk FISH, 32% had extramedullary disease (EMD) at Tec initiation, and 42% were penta-refractory. Compared to the cohort without prior BCMA-DT (n=192), patients who were treated with prior BCMA-DT were more likely to have high risk FISH (61% vs 49%, p=0.02), and higher median number of prior LOT (7 vs 5, p <0.001). The specific types of prior BCMA-DTs with the respective overall response rate (ORR) to the most recent prior BCMA-DT were: antibody drug conjugate only (ADC, n=47, ORR 43%), chimeric antigen receptor T-cell therapy only (CAR T, n=99, ORR 86%), BsAb only (n=6, ORR 100%), ADC + CAR T (n=36, ORR 56%), and other ADC/CAR T/BsAb combinations (n=5, ORR 60%).

Median follow up was 9.9 (95% CI:9.5-10.6) months. Patients with prior receipt of BCMA-DT had a lower ORR (51.4% vs 61.5%; p=0.012) and ≥very good partial response rate (39.4% vs 52.6%, p=0.009), but similar ≥complete response rate (22.3% vs 24%; p=0.78) to Tec compared to those without prior BCMA-DT. Moreover, patients with prior BCMA-DT had worse median PFS compared to patients without prior BCMA-DT (prior BCMA-DT: 4.6 months, 95% CI: 2.7-7.5; without prior BCMA-DT: 8.2 months, 95% CI: 5.7-12.2; p=0.017). On multivariable analysis incorporating prior BCMA-DT, age, cytogenetics, EMD, and ECOG PS, receipt of prior BCMA-DT was not independently associated with PFS (HR 1.25, 95% CI 0.95-1.64, p=0.1). The estimated 1-year OS rate was 58.9% (95% CI: 51.64-67.2) for the prior BCMA-DT group vs 65.1% (95% CI: 58.1-73.1) for the group without prior BCMA-DT, p=0.16.

For the prior BCMA-DT cohort, response rates to Tec were numerically higher in patients who received CAR T (ORR 51.2%) followed by ADC (ORR 45.5%), and bispecific (ORR 30%) as their most recent prior BCMA-DT (p=0.39). No significant difference in PFS was noted when stratifying patients by number of prior BCMA-DTs, types of all prior BCMA-DTs received, type of most recent prior BCMA-DT, or depth of response to most recent BCMA-DT. Patients who responded to Tec had a numerically longer median time from most recent BCMA-DT exposure to Tec initiation compared to non-responders: 10.5 vs 7.5 months, p=0.48. We found that the optimal cut-off for time from last BCMA-DT exposure to Tec initiation was 8.7 months. Patients with > 8.7 months between last exposure to prior BCMA-DT and Tec initiation had a superior median PFS with Tec (8.1 months, 95% CI: 4.6-11.7) compared to patients with < 8.7 months from last exposure to prior BCMA-DT (2.5 months, 95% CI: 1.1-5.7), p=0.001.

The toxicity profile for patients with prior BCMA-DT was similar to those who had not received a prior BCMA-DT. Grade ≥2 CRS occurred in 8.7% vs 13% (p=0.18), and grade ≥2 ICANS in 7.7% vs 6.7%, (p=0.85) of patients with and without prior BCMA-DT, respectively. Patients in the prior BCMA-DT cohort were more likely to have grade 3 thrombocytopenia in the first 30 days after Tec initiation (10.7% vs 6.6%; p=0.08).

Conclusion: This is the largest study to date of any BCMA-directed BsAb among BCMA-exposed patients. Receipt of prior BCMA-DT was associated with a trend toward worse PFS, although not statistically significant, and lower likelihood of attaining an overall response. Waiting >9 months between sequencing BCMA therapies may be associated with improved PFS.

D.D., M.A.V.M., J.A.D: co first authors; F.A., C.F., L.S.: co senior authors

Disclosures: Davis: Janssen Biotech: Speakers Bureau. Afrough: Bristol-Myers Squibb: Honoraria, Other: Data safety monitoring/advisory board; Karyopharm: Honoraria, Other: Data Safety Monitoring/Advisory Board; Janssen: Research Funding; K36 Therapeutics: Research Funding; Adaptive Biotechnology: Research Funding; AbbVie: Research Funding; Sanofi: Honoraria, Other: Data safety monitoring/advisory board. Banerjee: Adaptive; BMS; Caribou Biosciences; Genentech; GSK; JNJ / Janssen; Karyopharm; Legend Biotech; Pfizer; Sanofi; SparkCures: Consultancy; Abbvie; JNJ; Novartis; Pack Health; Prothena; Sanofi: Research Funding. Khouri: GPCR Therapeutics: Honoraria; Janssen: Consultancy; Legend Biotech: Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Grajales-Cruz: Sanofi: Honoraria, Other: Data Safety Monitoring/Advisory Board; Janssen: Honoraria, Other: Data Safety Monitoring/Advisory Board; Cellectar Biosciences: Honoraria, Other: Data Safety Monitoring/Advisory Board, Research Funding; Amgen: Honoraria; Pfizer: Honoraria, Other: Data Safety Monitoring/Advisory Board. Julian: Pfizer: Membership on an entity's Board of Directors or advisory committees; BioLine Rx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Gaballa: GLG: Consultancy; Guidepoint: Consultancy; Boxer Capital, LLC: Consultancy; Bristol Myers Squibb: Consultancy. Raza: Prothena Biosciences: Consultancy; Pfizer: Consultancy, Honoraria; Kite Pharma: Consultancy. Mikkilineni: Legend Biotech: Consultancy, Other: advisory board at ASH December 2023; BiolineRx: Consultancy, Other: advisory board at ASH December 2023. Kaur: Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria; Kedrion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Arcellx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Cellectar Biosciences: 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. Castaneda: Janssen: Consultancy; Legend Biotech: Consultancy; BMS: Consultancy. Rossi: Adaptive, BMS, Janssen, Karyopharm, JNJ, and Sanofi: Consultancy. Lin: Autolus: Consultancy; Rigel: Consultancy; ADC Therapeutics: Consultancy. Forsberg: University of Colorado: Ended employment in the past 24 months; Colorado Blood Cancer Institute: Current Employment; Johnson and Johnson, BMS: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lin: Regeneron: Consultancy; Sanofi: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Legend: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy. Atrash: Karyopharm: Research Funding; Janssen: Honoraria; Amgen: Research Funding; GSK: Research Funding. Sborov: Society of Utah Medical Oncology: Membership on an entity's Board of Directors or advisory committees; Binaytara Foundation: Honoraria; Parexel, Keosys: Other: IRC; Genentech, Inc.: Consultancy; Abbvie: Consultancy; Arcellx: Consultancy; Janssen: Consultancy; Legend Biotech: Consultancy; Pfizer: Consultancy, Research Funding; AstraZeneca: Consultancy; Bioline: Consultancy; University of Utah, Huntsman Cancer Institute: Current Employment; Bristol Myers Squibb: Consultancy; GlaxoSmithKline: Consultancy; Sanofi: Consultancy. Shain: BMS: Consultancy, Research Funding; Glaxo Smith Kline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Takeda: Consultancy; Karyopharm: Research Funding; Amgen: Research Funding; Abbvie: Research Funding; Karyopharm, Janssen, Adaptive Biotechnologies, GlaxoSmithKline, BMS, Sanofi, and Regeneron: Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotech: Consultancy. Voorhees: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Consultancy. Richard: Heidelberg Pharma: Research Funding; C4 Therapeutics: Research Funding; Gracell Therapeutics: Other: Steering Committee, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Garfall: Tmunity Therapeutics: Research Funding; Novartis: Research Funding; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Crispr: Research Funding. Hansen: Janssen: Consultancy; BMS: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Pfizer: Consultancy. Sidana: Sanofi: Consultancy; Novartis: Research Funding; Janssen: Consultancy, Research Funding; Kite, A Gilead company: Consultancy; BMS: Consultancy, Research Funding; Oncopeptides: Consultancy; Takeda: Consultancy; Regeneron: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; BiolineRx: Consultancy; Legend: Consultancy. Patel: Johnson & Johnson (Janssen): Consultancy; Abbvie: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Caribou Sciences: Consultancy; Poseida: Consultancy; Pfizer: Consultancy; AstraZeneca: Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; Genentech: Consultancy; Takeda: Consultancy; Oricel: Consultancy, Other: Chair of scientific board. Cowan: Abbvie: Research Funding; Juno/Celgene: Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Regeneron: Research Funding; IgM biosciences: Research Funding; BMS: Consultancy, Research Funding; Nektar: Research Funding; Caelum: Research Funding; Harpoon: Research Funding; HopeAI: Consultancy, Current holder of stock options in a privately-held company; Janssen: Consultancy, Honoraria, Research Funding; Sebia: Consultancy. Anderson: Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: 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, Other: DSMB; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Lee: Pfizer: Consultancy; Allogene: Consultancy; Abbvie: Consultancy; Takeda: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Regeneron: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Amgen: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy. Anwer: BMS: Consultancy. Ferreri: Affimed: Current holder of stock options in a privately-held company; Janssen: Consultancy. Shune: BMS: Membership on an entity's Board of Directors or advisory committees; Norvatis: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH