Promising New Teclistamab Combo Therapy for Myeloma Shows Early Success

Introduction to Teclistamab Combo Therapy

Teclistamab (Tecvayli) combined with daratumumab (Darzalex) and lenalidomide (Revlimid) has shown encouraging results in a study involving patients with newly diagnosed multiple myeloma, who are not eligible for a transplant. This innovative treatment approach aims to provide effective therapy options for older patients or those with specific health constraints that make them ineligible for traditional stem cell transplants.

Phases and Patient Demographics

The findings presented at the 2024 ASCO Annual Meeting encompassed data from cohort 1 of the phase 3 MajesTEC-7 trial. A total of 26 patients with newly diagnosed multiple myeloma participated, with a median age of 72.5 years, highlighting the prevalence of older patients in such trials.

Among these, 80.8% were aged 70 years or older, and 84.6% were determined to be transplant-ineligible. The initial round of treatments included a median of 15 cycles of the combined therapy.

Safety and Tolerability

All participants reported treatment-related side effects, with 92.3% experiencing serious adverse events (grade 3 or 4). Infections were notably common, affecting all patients, with a significant portion experiencing severe infections, including cases of COVID-19.

Interestingly, while early cycles showed a higher incidence of infections, the cumulative exposure to the drug combination did not significantly increase the risk of severe infections over time. Supplementing with intravenous immunoglobulin and early infection prophylaxis was recommended to mitigate these risks.

Cytokine Release Syndrome and Immune Effects

Nearly 62% of patients experienced cytokine release syndrome (CRS), predominantly during the first cycle. All cases, however, resolved, and the majority were mild (grade 1 or 2). There was only one reported case of grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS), which also occurred during the initial cycle.

Effectiveness and Response Rates

The study reported an impressive overall response rate of 92.3%, with 80.8% of patients achieving complete responses or better. Very good partial responses or better were noted in the vast majority of patients. There were no instances of disease progression in this cohort.

The median time to initial response was one month, with the best responses typically observed around 6.5 months into treatment.

Progression-Free Survival

During the follow-up period, which extended up to 15.4 months, only one instance of progression-free survival event was observed, pointing to the potential long-term benefits of this treatment approach. The 12-month duration of response and progression-free survival rates were reported at 100% and 96.2%, respectively.

Study Protocol and Dosing Schedules

Participants in this safety run-in phase received an initial “step-up” dose of teclistamab, with adjustments made over subsequent cycles. Standard dosages of daratumumab and lenalidomide were administered alongside.

The dosing regimen was carefully calibrated to enhance safety and effectiveness, continuing until patients experienced intolerable side effects, disease progression, or other adverse outcomes.

Comparative Cohorts and Adjustments

The MajesTEC-7 trial also included additional cohorts comparing teclistamab with other therapeutic agents like darolutamide and talquetamab. These variations aimed to establish the best protocol for future randomized studies.

However, certain approaches, such as the use of lenalidomide before the bispecific therapy, were found to increase the risk of serious side effects and infections, leading to adjustments in the treatment protocol for forthcoming phases of the trial.

Conclusion and Next Steps

The promising outcomes from this early-phase trial suggest that the teclistamab, daratumumab, and lenalidomide combination could become a viable treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma.

Ongoing monitoring and further research will be crucial to confirm these findings and refine the treatment protocols to maximize patient benefits while minimizing risks.