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

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.

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:BMS: Consultancy; Legend biotech: Consultancy; Pfizer: Consultancy; Janssen: Consultancy; Sanofi: Consultancy, Research Funding, Speakers Bureau.