Teclistamab Provides Deep, Durable Response Among Heavily Pretreated Patients With R/R Multiple Myeloma

Real-World, Multi-Institutional Study Results

Teclistamab therapy yields rapid achievement of deep hematologic response among heavily pretreated patients with relapsed/refractory (R/R) multiple myeloma (MM), according to a multi-institutional real-world study.

“A critical gap still remains regarding data on safety and efficacy of standard-of-care teclistamab since its approval in the US. Real-world data on safety and efficacy of teclistamab is critically important,” explained Meera Mohan, MD, MS, FACP, Medical College of Wisconsin, Milwaukee, Wisconsin, and colleagues.

Here, study authors report the largest real-world evaluation yet on the safety and efficacy of standard-of-care teclistamab in R/R MM since its accelerated approval by the FDA. The study focused on the safety and efficacy of standard-of-care teclistamab in a heavily pretreated patient population, including all consecutive patients that received at least 1 dose of teclistamab up until August 2023. Investigators included 110 patients; 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies.

The overall response rate (ORR) was measured as the proportion of patients achieving partial remission (PR), very good partial remission (VGPR), or complete remission (CR) at any time. As a baseline comparison, study authors also assessed the characteristics of the patients included in this analysis against those in the pivotal MajesTEC-1 clinical trial, which examined the safety, tolerability, and preliminary efficacy of teclistamab in this patient population.

Results demonstrated that the ORR in this study’s cohort was 62%, with a ≥ VGPR rate of 51%. The ORR among patients with and without prior BCMA-targeted therapies was 54% vs 67%, respectively (P = 0.23). At a median follow-up of 3.5 months (range, .39 to 10.92), the estimated 3-month and 6-month progression free survival (PFS) was 57% (95% confidence interval [CI], 48% to 68%) and 52% (95% CI, 42% to 64%) respectively.

Safety measurements indicated that the incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) was 56% and 11%, respectively, with grade ≥3 CRS and ICANS noted in 3.5% and 4.6% of patients, respectively. Additionally, 78 unique infections were diagnosed among 44 patients, with the incidence of all-grade and grade ≥3 infections being 40% vs 26%, respectively.

Primary prophylaxis with intravenous immunoglobulin (IVIG) was associated with a significantly lower infection risk on multivariate analysis (hazard ratio [HR] 0.33; 95% CI, .17 to .64; P = 0.001).

Study authors concluded the trial with 3 key findings. First, despite including a more heavily pre-treated patient population compared to the MajesTEC-1 trial with greater than 2-fold higher incidence of patients with penta-drug-refractory disease, the proportion of patients who achieved a VGPR or better was comparable to MajesTEC-1 (51% vs 59%, respectively). Second, while the overall incidence of ≥ grade 3 CRS and ICANS remained low, these measurements were substantially higher compared to the MajesTEC-1 trial, with incidences of 3.6% and 4.5% respectively (compared to 0.6% for each in MajesTEC-1). Lastly, the incidence of all grades and ≥grade 3 infections were lower at 40% and 26%, respectively, in this real-world experience, with primary intravenous immunoglobulin (IVIG) prophylaxis associated with a significantly lower incidence of grade 3 or higher infections.

Mohan and colleagues concluded, “In summary, our study demonstrates that teclistamab leads to rapid achievement of deep hematologic response in heavily [pretreated] MM, with response rates comparable to MajesTEC-1 trial.”

“While the incidence of severe CRS/ICANS is substantially higher in the real-world compared to what was seen in clinical trials, stringent infection prophylaxis, especially primary IVIG prophylaxis, can significantly lower infection-related morbidity and mortality,” they added. “Future studies should prospectively assess the impact of primary IVIG prophylaxis along with limited-duration treatment to potentially avoid T-cell exhaustion and allow safer delivery of BCMA [bispecific antibodies].”

Source:

Mohan M, Monge J, Shah N, et al. Teclistamab in relapsed refractory multiple myeloma: Multi-institutional real-world study. Blood Cancer J. 14, 35 (2024). doi: 10.1038/s41408-024-01003-z