Clinical Research · global
Dual-Targeted Antibodies Join Forces to Reduce the Risk of Multiple Myeloma Progression, but Full Data Have Yet to Emerge
Preliminary results from a Phase 3 trial show that off-the-shelf immunotherapies simultaneously targeting BCMA and GPRC5D may move bispecific antibodies into earlier lines of treatment; however, median survival and detailed safety data have yet to be disclosed.
Patients with relapsed or refractory multiple myeloma often face progressively fewer options after several rounds of treatment. Preliminary results from Johnson & Johnson’s Phase 3 MonumenTAL-6 trial point to a more aggressive approach: using two bispecific antibodies to mobilize T cells simultaneously against different markers on the surface of myeloma cells.
Among adults who had received one to four prior lines of therapy and had been treated with an anti-CD38 antibody and lenalidomide, the combination of teclistamab and talquetamab reduced the relative risk of disease progression or death by 89% compared with the investigator’s choice of the standard EPd or PVd regimen, with a hazard ratio of 0.11 (95% confidence interval, 0.08 to 0.16; p<0.0001). The relative risk of death was reduced by 62%, with a hazard ratio of 0.38. These figures come from the first interim analysis, and the independent data monitoring committee has recommended unblinding the trial.
The two drugs target different antigens. Teclistamab links CD3 on T cells with BCMA, which is commonly found on myeloma cells; talquetamab brings CD3 together with GPRC5D. The purpose of this dual-targeting strategy is to reduce the opportunity for cancer cells to evade immune attack simply by escaping a single marker when tumors are heterogeneous or antigen expression changes. Both are readily available antibody therapies and, unlike personalized cell therapies, do not require the collection and preparation of a patient’s cells.
MonumenTAL-6 is a global, randomized, three-arm study planned to enroll approximately 795 participants across 211 centers. In addition to the dual-antibody arm, another experimental arm combines talquetamab with pomalidomide; this arm also met the primary endpoint of progression-free survival, reducing the risk of disease progression or death by 73%. In the control arm, physicians chose either elotuzumab, pomalidomide, and dexamethasone, or pomalidomide, bortezomib, and dexamethasone.
The most important gap at present is that the announcement provided only summary results. Median progression-free survival and overall survival, follow-up duration, the actual number of events in each arm, treatment discontinuations, and subgroup results were not disclosed; ClinicalTrials.gov has also not yet posted the full trial results. Therefore, the 89% and 62% figures represent relative differences in risk during the follow-up period and cannot be directly interpreted as equivalent increases in patient cure rates or absolute survival gains.
Safety likewise cannot be assessed without a full report. The company stated only that the overall safety profiles of the two experimental arms were consistent with the existing data for each drug and has not yet disclosed the rates of serious infections, cytokine release syndrome, neurotoxicity, cytopenias, or treatment discontinuation. Only if subsequent scientific meetings and regulatory reviews confirm that the efficacy is durable and that the toxicity of dual immune stimulation can be appropriately managed in clinical practice could this combination truly change treatment sequencing for multiple myeloma at an earlier stage of relapse.