Background: Teclistamab (Tec), a first-in-class BCMA bispecific T-cell antibody, received regulatory approval for the treatment of RRMM based on the MajesTEC-1 study [Moreau et al, NEJM, 2022] which demonstrated an overall response rate (ORR) of 63% and median progression free survival (PFS) of 11.3 months. However, less than 15% (N=24) of patients (pts) enrolled in MajestTEC-1 were ≥75 years, an age cohort that is often underrepresented in clinical trials and comprises approximately one third of MM pts at diagnosis [SEER 22 2017-2021]. In this multicenter retrospective study, we report the real-world safety and efficacy of a large cohort of elderly (≥75 years) RRMM pts treated with Tec.

Methods: Pts with RRMM who received standard-of-care Tec across 13 U.S. academic institutions were included in the study. The follow-up data cutoff was 30 April 2024. Pts were divided by age into two groups: age <75 years (<75 group) and age ≥75 years (≥75 group). High-risk cytogenetic abnormalities (HRCA) were defined as the presence of del(17p), t(4;14), t(14;16) and/or gain or amplification of 1q21. Disease response and progression was evaluated using IMWG criteria. Time-to-event analyses were evaluated using the Kaplan-Meier method. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) assessment was based on the American Society for Transplantation and Cellular Therapy consensus grading.

Results: Among 385 pts, 83 (22%) were in the ≥75 group (median age 78, range 75-92) and 302 (78%) in the <75 group (median age 65, range 31-74). Compared to pts in the <75 group, those in the ≥75 group were more often white (78% vs. 63%, p=0.009). Both the ≥75 and <75 age groups had a median of 6 prior lines of therapy, a similar proportion with ECOG ≥2 at start of Tec (29% vs. 24%, respectively; p=0.37), and a high proportion of pts with triple-class-refractory disease (77% vs. 85%, p=0.06) and pts who would have been ineligible MajesTEC-1 (73% vs. 80%, p=0.20). In contrast, pts in the ≥75 group had a lower incidence of adverse MM risk factors compared to the <75 group, including HRCA (44.6% vs. 57.9%, p=0.03), ultra high-risk (≥2 HRCA) MM (12% vs. 24%, p=0.02), extramedullary disease (22% vs. 40%, p=0.02), hemoglobin <8 g/dL (10% vs. 21%, p=0.02) or albumin <3 g/dL (6% vs. 19%, p=0.04) at the time of starting Tec. Moreover, a lower proportion of pts in the ≥75 group had prior autologous stem cell transplantation (43% vs. 72%, p<0.0001) or prior BCMA-directed therapy (33% vs. 55%, p=0.0003). The median time from diagnosis to start of Tec was longer for pts in the ≥75 group (7.21 years vs. 5.81 years, p=0.02).

There was no significant difference in rates of any-grade CRS (52% vs. 59%, p=0.27), CRS grade 2-4 (10% vs. 11%, p=0.74) or any-grade ICANS (19% vs. 13%, p=0.12) between the ≥75 and <75 age groups, respectively. Four pts in the entire cohort developed CRS grade 3-4, one of whom was in the ≥75 group. Ten pts developed grade 3 ICANS (none grade 4), three of whom were in the ≥75 group.

There was no significant difference between the ≥75 group and <75 group in ORR (62% vs. 53%, p=0.17) and ≥very good partial response (VGPR) rate (53% vs. 44%, p=0.14).

After a median follow-up period of 9.9 months (95% CI 9.6-10.6 months), the median PFS in the ≥75 group was 10.7 months (95% CI 6.6-NR) vs. 5.2 months (95% CI 6.6-NR) in the <75 group (p=0.005). At the time of data cut-off, the median overall survival (OS) for pts in the ≥75 group had not been reached (95% CI NR - NR) compared to 16.1 months (95% CI 14.0 - NR) in the <75 group (p=0.048).

In multivariable analysis for the entire cohort, age ≥75 was not significantly associated with either PFS (HR 0.87, 95% CI 0.54-1.39; p=0.55) or OS (HR 0.60, 95% CI 0.30-1.19; p=0.15).

Conclusions: This analysis of a large cohort of RRMM pts treated with Tec in the real-world setting demonstrates comparable efficacy and safety outcomes in elderly (aged ≥75 years) pts to those reported in the overall study population of MajesTEC-1. The adverse baseline disease characteristics and inferior efficacy in pts <75 years age compared to ≥75 years likely reflect patient selection and prescribing patterns in the early era of access to commercial BCMA bispecific therapy with Tec. In multivariable analysis there was no significant impact of age ≥75 on survival outcomes.

OP, DD & LF: co-first authors. KKP, HCL & AGC: co-senior authors

Disclosures

Davis:Janssen Biotech: Speakers Bureau. Afrough:Karyopharm: Honoraria, Other: Data Safety Monitoring/Advisory Board; Janssen: Research Funding; K36 Therapeutics: Research Funding; AbbVie: Research Funding; Adaptive Biotechnology: Research Funding; Bristol-Myers Squibb: Honoraria, Other: Data safety monitoring/advisory board; Sanofi: Honoraria, Other: Data safety monitoring/advisory board. Banerjee:Abbvie; JNJ; Novartis; Pack Health; Prothena; Sanofi: Research Funding; Adaptive; BMS; Caribou Biosciences; Genentech; GSK; JNJ / Janssen; Karyopharm; Legend Biotech; Pfizer; Sanofi; SparkCures: Consultancy. Khouri:Legend Biotech: Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; GPCR Therapeutics: Honoraria; Janssen: Consultancy. Gaballa:GLG: Consultancy; Guidepoint: Consultancy; Boxer Capital, LLC: Consultancy; Bristol Myers Squibb: Consultancy. Julian:BioLine Rx: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Ferreri:Affimed Therapeutics: Current equity holder in private 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. Mikkilineni:BiolineRx: Consultancy, Other: advisory board at ASH December 2023; Legend Biotech: Consultancy, Other: advisory board at ASH December 2023. Kaur:Arcellx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite, a Gilead Company: Consultancy, 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; Bristol Myers Squibb: 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; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; AbbVie: Research Funding; Kedrion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Rossi:Adaptive, BMS, Janssen, Karyopharm, JNJ, and Sanofi: Consultancy. Raza:Pfizer: Consultancy, Honoraria; Prothena Biosciences: Consultancy; Kite Pharma: Consultancy. Lin:NexImmune: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; Genentech: Consultancy; Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Regeneron: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Legend: Consultancy. Atrash:Karyopharm: Research Funding; Janssen: Honoraria; Amgen: Research Funding; GSK: Research Funding. McGuirk:Novartis: Consultancy; Kite: Consultancy; Legend biotech: Consultancy; Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Sana technologies: Consultancy; Allo Vir: Consultancy; Envision: Consultancy; Autolus: Consultancy; BMS: Consultancy. Sborov:Arcellx: Consultancy; Society of Utah Medical Oncology: Membership on an entity's Board of Directors or advisory committees; University of Utah, Huntsman Cancer Institute: Current Employment; Genentech, Inc.: Consultancy; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Bioline: Consultancy; AstraZeneca: Consultancy; GlaxoSmithKline: Consultancy; Binaytara Foundation: Honoraria; Parexel, Keosys: Other: IRC; Legend Biotech: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; Sanofi: Consultancy. Voorhees:Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: 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; Lava Therapeutics: Consultancy; GSK: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy. Anwer:BMS: Consultancy. Alsina:Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Freeman:BMS: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy, Research Funding; Incyte: Consultancy; ONK therapeutics: Consultancy; Amgen: Consultancy; Roche/Genentech: Research Funding; Celgene: Consultancy; Sanofi: Consultancy. Garfall:Tmunity Therapeutics: Research Funding; Novartis: Research Funding; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Crispr: Research Funding. Sidana:Abbvie: Consultancy; BiolineRx: Consultancy; Novartis: Research Funding; Kite, A Gilead company: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; BMS: Consultancy, Research Funding; Regeneron: Consultancy; Takeda: Consultancy; Janssen: Consultancy, Research Funding; Pfizer: Consultancy; Legend: Consultancy. Anderson:GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; 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; 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. 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. Patel:Sanofi: Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; Abbvie: Consultancy; Oricel: Consultancy, Other: Chair of scientific board; Pfizer: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Johnson & Johnson (Janssen): Consultancy; Caribou Sciences: Consultancy; AstraZeneca: Consultancy; Merck: Consultancy; Takeda: Consultancy; Poseida: Consultancy; Genentech: Consultancy. Lee:Abbvie: Consultancy; Pfizer: Consultancy; Allogene: Consultancy; Regeneron: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Research Funding; Janssen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy. Grajales-Cruz:Pfizer: Honoraria, Other: Data Safety Monitoring/Advisory Board; Sanofi: Honoraria, Other: Data Safety Monitoring/Advisory Board; Cellectar Biosciences: Honoraria, Other: Data Safety Monitoring/Advisory Board, Research Funding; Janssen: Honoraria, Other: Data Safety Monitoring/Advisory Board; Amgen: Honoraria.

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2024
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