Tec-Dara Combo More Effective for Relapsed or Refractory Multiple Myeloma
Patients with relapsed or refractory (R/R) multiple myeloma who received a combination of teclistamab, a bispecific monoclonal antibody, and daratumumab, a CD38-directed monoclonal antibody, were 83% more likely to be alive without disease progression compared with those who received standard second-line therapies at a median of nearly 35 months of follow-up, according to the results of a new trial presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.
The trial is the first to test a bispecific monoclonal antibody as early as the first relapse after initial treatment for multiple myeloma. Based on the findings, researchers suggest the combination of teclistamab and daratumumab, known as Tec-Dara, could represent a new standard of care for R/R multiple myeloma.
“We were surprised by the efficacy data because we didn’t expect such a magnitude of benefit,” said lead study author María-Victoria Mateos, MD, PhD, physician in the haematology department and professor of medicine at the University of Salamanca in Spain. “These are the best data we’ve seen in patients with R/R multiple myeloma after one line of therapy. Patients will live longer overall and with no worsening of quality of life.”
Multiple myeloma is a cancer that causes excessive production of plasma cells, crowding out the production of other types of blood cells and harming the body’s ability to fight infections. It is most common in older adults. Patients who relapse or experience an incomplete response to initial treatment often have their cancer return after subsequent therapies, pointing to a need for improved second-line treatments.
Teclistamab is approved by the U.S. Food and Drug Administration for R/R multiple myeloma after at least four prior lines of therapy. Daratumumab is a therapy targeting the CD38 protein that has been approved for use in combination with other therapies for newly diagnosed and R/R multiple myeloma. Laboratory studies have suggested that teclistamab and daratumumab may work synergistically to eradicate cancer to a greater extent than either agent individually.
To test this hypothesis, researchers randomized 587 patients with R/R multiple myeloma to receive either Tec-Dara or standard second-line therapies. For patients in the control arm, treating physicians chose between two standard three-agent combination therapies which included daratumumab with dexamethasone plus either pomalidomide or bortezomib (known as DPd or DVd, respectively).
Study participants had a median age of 64 with a range of 25-88, and all patients were R/R after one to three prior lines of therapy. Participants remained on their assigned treatment regimen unless they experienced intolerable adverse events, and were followed for a median of nearly 35 months.
The 36-month rate of progression-free survival, the study’s primary endpoint, was achieved in 83.4% of participants who received Tec-Dara and 29.7% of those receiving DPd/DVd, a substantial improvement in favor of Tec-Dara. This benefit was consistent across subgroups of patients by age, prior treatment, tumor genetics, and other factors.
In addition to being a highly efficacious treatment for R/R multiple myeloma as early as the first relapse, researchers noted that the Tec-Dara combination could be more accessible than other second-line therapies for multiple myeloma as it could be delivered in community settings, not just academic centers.
Tec-Dara outperformed DPd/DVd in terms of the trial’s secondary efficacy endpoints as well as quality of life outcomes and had a safety profile comparable to the control arm. Patients receiving Tec-Dara were significantly more likely to achieve a complete response or better, which occurred in 81.8% of patients receiving Tec-Dara and 32.1% among the control arm. They were also more likely to test negative for minimal residual disease (MRD), a sensitive test for remaining cancer cells, with 58.4% of those in the Tec-Dara arm achieving MRD-negativity compared with 17.1% in the control arm. Overall survival was also higher in the Tec-Dara arm, with 83.3% of patients in this group being alive at 36 months compared with 65.0% in the control arm.
The results showed comparable rates of treatment-emergent adverse events, with 95.1% of patients in the Tec-Dara arm and 96.6% of those in the control arm experiencing grade 3-4 adverse events. Rates of serious adverse events and discontinuations due to adverse events were also comparable between groups, researchers reported.
The rate of infections was higher among those receiving Tec-Dara, with 96.5% of patients in this group experiencing infections compared with 84.1% in the control group. The onset of higher-grade infections decreased over time, and researchers noted that strategies for managing infections also improved over the course of the study. Low-grade cytokine release syndrome (CRS) was also common, with grade 1-2 CRS occurring in 60.1% of those receiving Tec-Dara.
One limitation of the study is that patients refractory to daratumumab were not included in the trial. However, some patients (5%) had received daratumumab as part of their first-line therapy and benefited equally from the Tec-Dara combination.
Dr. Mateos noted that future studies could help clarify how doctors might select which patients would benefit most from the Tec-Dara combination in comparison to other therapies. Trials involving other bispecific antibody combinations are also underway and could shed additional light on the optimal use of such combinations as early as the first relapse.
Source: American Society of Hematology
