Toxicity and Efficacy Outcomes of Teclistamab in Patients with Relapsed-Refractory Multiple Myeloma (RRMM) Above the Age of 70 Years: A Multicenter Study
Authors: Dima Danai , Sannareddy Aishwarya , Ahmed Nausheen , Davis James A , Shaikh Hira , Mahmoudjafari Zahra , Duco Marissa , Khouri Jack , Kaur Gurbakhash , Lochner Jonathan , Anwer Faiz , Afrough Aimaz , Valent Jason , Hashmi Hamza , Abdallah Al-Ola 
Published: December 2023

Introduction: Older patients (&gt;70 years old) are often considered ineligible for intensive treatments including autologous stem cell transplant (ASCT) and chimeric antigen receptor T-cell (CAR-T) therapies, having a relatively poor performance status and concomitant comorbidities. Therefore, the interest in this age group has been shifted in utilization of novel therapies with a less toxic side effect profile and less risk for serious complications. Teclistamab is a novel B-cell maturation antigen (BCMA)-directed bispecific antibody that received approval for the treatment of patients with RRMM after ≥4 prior lines of therapy (LOT) based on the results of the MajesTEC-1 trial. In this retrospective study, we aimed to analyze real-world data on the efficacy and toxicity profile of teclistamab in a population of older RRMM patients, and compare them with younger individuals.

Methods: Five US academic centers, part of the US Myeloma Innovations Research Collaborative (USMIRC) contributed data to this analysis. One hundred and two patients with RRMM who received teclistamab as of 7/1/2023 were included in this study. Baseline characteristics were outlined by descriptive analysis. Responses, including overall response rate (ORR) and compete response rate or better (≥CR) were assessed using the International Myeloma Working Group (IMWG) criteria. Adverse events were graded based on the CTCAE v5.0 criteria. Statistical analysis was done with Chi-squared test and Kaplan-Meier method for progression-free survival (PFS) calculation.

Results: Of the 102 patients included in this study, 33 (32%) were above the age of 70 years (older) with a median age of 75 (range 71-87) years. Disease characteristics of the older patient population were notable for 58% with high-risk cytogenetics as defined by presence of del(17p), t(4;14), t(14;16) and/or t(14;20), and 39% with extramedullary disease (EMD) prior to teclistamab initiation. Patients were heavily pretreated with a median of 6 (range 4-17) prior LOT; 58% had undergone prior ASCT and 97%, 58%, and 58% were triple, penta, and BCMA-directed therapy (BDT) refractory, respectively. Compared to patients with age &lt;70 years (n=69), older patients were more likely to have a worse performance status (ECOG ≥2) (45% vs 26%, p=0.05); other baseline characteristics including high-risk cytogenetics, stage III (per revised international staging system) disease, extramedullary disease, triple, penta- and BDT-refractoriness status were comparable between the two groups (Table 1). Median follow-up time for the entire cohort was 3.2 months. Patients with age &gt;70 years had a comparable ORR (70% vs 61%, p=0.37), and ≥CR (30% vs 28%, p=0.8) rates to those with younger age. In addition, the two subgroups had comparable median estimated PFS (5.4 vs 3.8 months, p=0.61) (Figure 1). Cytokine release syndrome (CRS) in most cases was grade 1-2, and CRS rates were similar between the older and younger patient groups (67% vs 64%, p=0.7). Likewise, most immune effector cell-associated neurotoxicity syndrome (ICANS) events were grade 1-2, and rates were comparable between the two groups (21% vs 11%, p=0.17, Table 1). Patients older than 70 years were more likely to have grade 3-4 thrombocytopenia within the first 90 days from teclistamab initiation (27% vs 12%, p=0.05), while the rest of grade 3-4 cytopenias were not different between the two cohorts. Infection rates (33% vs 26%, p=0.46) and hospital readmission rates (36% vs 23%, p=0.16) were comparable between the older and younger patients, respectively.

Conclusions: This is the first and largest multicenter retrospective analysis characterizing a real-world cohort of patients who received teclistamab. Based on our results, older age (&gt;70 years) does not appear to affect response outcomes or PFS. For the most part, the safety profile appears similar, however patients older than 70 years were more likely to develop grade 3-4 thrombocytopenia. Importantly, the infection rates were not significantly different between the two groups, further supporting the broad use of teclistamab in older patients with RRMM.