Teclistamab Shows Promising Efficacy for High-Risk Myeloma Patients

In a significant advancement for the treatment of multiple myeloma, a retrospective study has demonstrated that Teclistamab-cqyv (Tecvayli), a bispecific T-cell engager, can lead to clinically meaningful responses in patients who were previously ineligible for the MajesTEC-1 clinical trial. This study, published in the journal Blood Cancer Discovery on July 9, 2025, reveals the efficacy of Teclistamab in a patient demographic characterized by high-risk factors and extensive prior therapy, including those previously treated with B-cell maturation antigen (BCMA) therapies.

The research, led by Dr. Beatrice M. Razzo, an assistant professor at Thomas Jefferson University, analyzed data from 509 multiple myeloma patients across 15 U.S. academic medical centers. Remarkably, 89% of the participants would have been excluded from the MajesTEC-1 trial, primarily due to prior BCMA-targeting therapy, cytopenias, or a performance status classified as two or higher. The findings highlight the pressing need to understand how to optimize the use of Teclistamab in real-world clinical settings, particularly for patients with complex treatment histories.

The results indicate that Teclistamab effectively reduced disease burden by at least 50% in 53% of evaluable patients, while 45% of subjects experienced a reduction of 90% or more, qualifying for a “very good partial response” according to standard criteria. Notably, at a median follow-up of 10.1 months, half of the patients remained progression-free for at least 5.8 months, and an estimated 61% survived after one year.

Despite the higher prevalence of adverse factors in this cohort, the safety profile of Teclistamab appeared consistent with findings from the MajesTEC-1 trial. Among the 56 patients who would have qualified for MajesTEC-1, overall response rates were comparable, with 61% responding to treatment versus 63% in the trial population.

The study also revealed that Teclistamab provided substantial benefits to patients with prior exposure to BCMA-targeting therapies, with 40% of those previously treated with CAR T cells or the antibody-drug conjugate belantamab mafodotin achieving very good partial responses. However, prior treatment with BCMA-targeting therapies within nine months of starting Teclistamab was associated with lower response rates, suggesting that timing and treatment sequencing may play critical roles in patient outcomes.

Dr. Razzo emphasized the importance of these findings, stating, "Teclistamab remains an important treatment option for patients with late-line, relapsed or refractory multiple myeloma, and should be considered even in those with prior BCMA exposure or markers of high disease burden and inflammation."

While this study offers promising insights, it also highlights the need for further research to refine treatment protocols and address the limitations inherent in real-world data, including the non-standardized nature of the data collected and the absence of centralized review processes. Dr. Razzo and her team are currently conducting a phase II trial focused on evaluating limited-duration drug dosing in advanced multiple myeloma patients, aiming to optimize therapeutic strategies in this vulnerable population.

The findings underscore the evolving landscape of multiple myeloma treatment, particularly for high-risk patients who have been historically underserved in clinical trials. As Teclistamab continues to represent a beacon of hope, the medical community remains vigilant in its pursuit of effective strategies to manage this complex malignancy.