Teclistamab-cqyv is the first bispecific T-cell engager antibody that targets both B-cell maturation antigen (BCMA) proteins on myeloma cells and CD3 proteins on T cells. It was approved by the U.S. Food and Drug Administration in 2022 for treatment of patients with relapsed or refractory multiple myeloma based on findings from the MajesTEC-1 trial.
A recent retrospective study evaluated the real-world safety and efficacy of teclistamab, including its activity in patients who were not represented in the phase I/II MajesTEC-1 trial. Researchers reported that the agent produced clinically meaningful responses in heavily pretreated patients with relapsed or refractory multiple myeloma, including those with prior BCMA therapy. The findings also showed a complex interplay among disease burden, T-cell fitness, inflammation, recent exposure to prior BCMA-directed therapies, and cytogenetic risk factors that influence patient outcomes. The study by Razzo et al was published in Blood Cancer Discovery.
Study Methodology
The researchers conducted a multicenter retrospective study from 15 academic medical centers in the United States Multiple Myeloma Immunotherapy Consortium. A total of 509 patients with relapsed or refractory multiple myeloma who received teclistamab between August 2022 and January 2024 were included in this retrospective analysis, half of whom had received at least six prior treatments. A total of 89% of these patients (n = 453) were ineligible for participation in the MajesTEC-1 trial. Overall, the patients in this study represented a higher-risk population, with more frail individuals enrolled and a greater prevalence of multidrug-refractory disease and cytogenetic abnormalities. Median age of the participants was 68 years, and 23% were aged 75 or older. A total of 19% of the patients were Black. High-risk features included extramedullary plasmacytomas in 202 patients (45%), ≥ 60% bone marrow plasma cell burden in 40 patients, high-risk cytogenetic features in 275 patients (54%), and at least two high-risk cytogenetic features in 108 patients (21%).
Responses to the therapy were assessed based on the International Myeloma Working Group criteria by each individual institution.
Key Results
Teclistamab reduced the disease burden by at least half in 53% (n = 270) of the 506 evaluable patients, with 45% (n = 228) experiencing at least a 90% reduction in disease burden. At a median potential follow-up of 10.1 months, half of the patients remained progression-free for at least 5.8 months, and an estimated 61% were alive at 1 year. Despite the high prevalence of patients with high-risk features, there appeared to be no increase in adverse event frequency compared with their prevalence in MajesTEC-1 and other real-world analyses of the bispecific antibody’s use. In addition, the 56 patients who would have been eligible for MajesTEC-1 had similar overall response rates as the trial participants, 61% and 63%, respectively.
Furthermore, regarding MajesTEC-1–ineligible patients, teclistamab also was of benefit to many patients previously treated with BCMA-targeting chimeric antigen receptor (CAR) T cells or the antibody-drug conjugate belantamab mafodotin-blmf. Of these patients, 40% experienced a very good partial response, including 43% of the 58 patients previously treated with belantamab mafodotin and 38% of the 104 patients previously treated with CAR T-cell therapy.
Further analyses found that patients who underwent prior BCMA-targeting therapy within 9 months of starting teclistamab experienced lower rates of very good partial response and shorter periods of progression-free survival. However, the researchers found that this therapeutic resistance occurred more often in the patients recently treated with CAR T-cell therapies than in those recently treated with belantamab mafodotin, who responded at a rate comparable to that in BCMA therapy–naive patients.
“Our findings significantly enhance the understanding of the safety and efficacy of teclistamab in real-world settings. We confirm that teclistamab is a safe and highly effective treatment option for patients with relapsed/refractory multiple myeloma. Furthermore, our results highlight the complex interplay between disease burden, T-cell fitness, inflammation, recent exposure to prior BCMA-directed therapies, and cytogenetic risk factors in influencing patient outcomes, providing valuable insights for optimizing the use of teclistamab in clinical practice,” concluded the study authors.
Disclosure: For full disclosures of the study authors, visit aacrjournals.org/bloodcancerdiscov.
