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3781 Efficacy and Safety of Teclistamab in Relapsed Refractory Multiple Myeloma: Long-Term Follow-up from a Real World Multi-Institutional Cohort

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, Health outcomes research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies, Adverse Events
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Metodi Balev, MD1, Nishi Shah, MBBS, MPH2, Mansi R. Shah, MD3, Anannya Patwari, MD4*, Aniko Szabo, PhD4*, Anita D'Souza, MD5, Asis Shrestha, MD6*, Binod Dhakal, MBBS7, Danny Luan, MD, MPH8, Dennis L Cooper, MD2, Frits van Rhee, MD, PhD6, Heloise Cheruvalath4, Jorge Monge, MD9, Mark Forsberg, MD2*, Maurizio Zangari, MD10, Sharmilan Thanendrarajan, MD6, Vineel Bhatlapenumarthi4*, Samer Al-Hadidi, MD6*, Suzanne Lentzsch, MD, PhD1, Divaya Bhutani, MD1, Rajshekhar Chakraborty, MD1, Carolina Schinke, MD10 and Meera Mohan, MD11

1Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY
2Montefiore Einstein Comprehensive Cancer Center, Blood Cancer Institute, Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
3Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
4Medical College of Wisconsin, Milwaukee, WI
5Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
6University of Arkansas for Medical Sciences, Little Rock, AR
7Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
8New York-Presbyterian Hospital/Weill Cornell Medicine, Astoria, NY
9New York-Presbyterian Hospital/Weill Cornell Medicine, New York, NY
10Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR
11Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI

Introduction: Teclistamab is a B cell maturation antigen (BCMA)-targeting bispecific antibody (bsAb) that is approved in patients with relapsed/refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy. In this study, we report long-term follow-up data regarding the safety and efficacy of teclistamab in a real-world multi-institutional cohort.

Methods: We performed a retrospective cohort study on 168 patients with RRMM who received at least one dose of teclistamab across 5 academic medical centers in the US. Infection incidence was evaluated from the date of teclistamab initiation through the date of last follow-up or 60 days after discontinuation of therapy. Responses were adjudicated as per International Myeloma Working Group (IMWG) criteria. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS).

Results: The median age of our cohort was 70 years (range: 31- 89) and 49% were female. Black patients constituted 25% of the cohort. Most patients (65%) had high risk cytogenetics and either triple-class refractory (83%) or penta-refractory (52%) disease. Extraosseous extramedullary disease (EMD) was seen in 43 patients (28%) prior to starting teclistamab, and relatively few patients had CNS involvement (1.8%), plasma cell leukemia (6.5%), or concomitant AL amyloidosis (4.2%). The median prior lines of therapy were 5 (range 1-12) with the majority having received at least one prior autologous stem cell transplantation (95%). At the time of teclistamab initiation, 92% of patients had evidence of progressive disease and 55 patients (33%) had received prior BCMA-targeted therapy. Among those with prior BCMA exposure, the most common therapy used was BCMA CAR T-cell therapy (n=34; 62%), followed by BCMA antibody-drug conjugate (ADC) (n=18; 33%), and BCMA bsAb (n=5; 9.1%). Notably, 2 patients received both prior BCMA CAR T and ADC.

Patients received a median of 15 teclistamab doses (range 1 - 49) and were followed for a median of 8.5 months from treatment initiation. The overall response rate (ORR) in our cohort was 71%, with a very good partial response (VGPR) or better in 60% of patients. The median time to best response was 2.94 months. No baseline clinical characteristic demonstrated a statistically significant association with ORR on multivariable analysis. Specifically, age (odds ratio (OR) 0.99, 95% CI 0.94-1.04, p = 0.67), prior BCMA-targeted therapy (OR 0.85, 95% CI 0.29-2.54, p = 0.77), and the presence of high-risk cytogenetics (OR 0.48, 95% CI 0.17-1.23, p = 0.14) were not significant predictors. In our cohort, the estimated PFS rates at 6 and 12 months were 58% and 49%, respectively, while the OS rates were 81% and 68%, respectively. The median PFS and OS was 12 months (95% CI, 7.1-15) and 18 months (15-NR) respectively.

The incidence of grade 1/2 cytokine release syndrome (CRS) was 53%, with only 1 patient (0.6%) experiencing grade 3 CRS. The incidence of grade 1/2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 7.2%, with 3 patients (1.8%) experiencing grade 3 ICANS. Of those with CRS/ICANS, 29 patients (17%) received systemic steroids and 45 patients (27%) received tocilizumab. Within this cohort, 99% of patients received herpes prophylaxis, 73% pneumocystis prophylaxis, 43% primary or secondary prophylaxis with intravenous immunoglobulin, 19% prophylactic antibiotics, and 16% antifungal prophylaxis. Overall, a total of 181 infections were diagnosed in 92 patients in this cohort, with 100 of these being ≥ grade 3 infections (55.2%), and 79% of infections confirmed microbiologically. The cumulative incidence of all-grade infections at 3 months and 6 months was 43% and 54% respectively, with the respective cumulative incidence of grade ≥3 infections being 23% and 34%. The estimated rate of all-grade and grade ≥3 infections per 100 days was 0.61 (±0.07) and 0.33 (±0.06) respectively. There were four grade 5 infections (2.2%) observed.

Conclusion: Despite a significantly higher proportion of patients with triple-class refractory and penta-refractory disease in our cohort compared to the MajesTEC-1 trial, teclistamab demonstrated a comparable ORR and ≥VGPR rate. Additionally, with the implementation of robust infection prophylaxis, the rates of all-grade and grade 3-5 infections were favorable compared to clinical trial data. Further follow-up data will be presented at the meeting.

Disclosures: Shah: Dedham Group: Honoraria; Bristol Myers Squibb: Consultancy, Research Funding; Targeted Oncology: Consultancy; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. D'Souza: Abbvie: Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Caelum: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Research Funding; Takeda: Research Funding. Dhakal: Pfizer: Consultancy, Honoraria, Speakers Bureau; Carsgen: Research Funding; Karyopharm: Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria; Acrellx: Research Funding; Sanofi: Research Funding; Medical College of Wisconsin: Current Employment; Bristol Myers Squibb: Honoraria, Research Funding; C4 therapeutics: Research Funding. van Rhee: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Castleman Disease Collaborative Network: Membership on an entity's Board of Directors or advisory committees; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Takeda: Consultancy; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Monge: Pfizer: Consultancy; Johnson & Johnson: Consultancy; Janssen: Consultancy. Zangari: Janssen Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lentzsch: PeerView, Clinical Care, Options (CCO), RedMed, Aptitude, Bio Ascend: Speakers Bureau; Pfizer, Regeneron, Janssen, GSK, Sanofi, BMS, Karyopharm, Antigia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caelum Bioscience: Patents & Royalties. Bhutani: Sanofi: Consultancy, Research Funding. Chakraborty: Adaptive: Consultancy; Janssen: Consultancy; Sanofi: Consultancy. Schinke: OncLive: Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Arcellx: Consultancy; Cancer Network: Honoraria. Mohan: Sanofi: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; Pfizer: Consultancy; Legend biotech: Consultancy; BMS: Consultancy.

*signifies non-member of ASH