J&J Multiple Myeloma Bispecific Antibody Combination Shows Advantage in Phase 3 Earlier-Line Trial

Treatment for multiple myeloma has advanced rapidly in recent years, with immunotherapies once largely reserved for later-line patients now being tested to see whether they can intervene earlier at critical moments of disease relapse. Johnson & Johnson announced on June 13 that the Phase 3 MonumenTAL-3 study showed its GPRC5D bispecific antibody Talvey, used in combination with the subcutaneous CD38 antibody Darzalex Faspro, delayed disease progression compared with standard therapy in patients with relapsed or refractory multiple myeloma who had received at least one prior line of treatment.

The study compared two Talvey combinations: Talvey plus Darzalex Faspro, or the same combination with pomalidomide added, against a control regimen of Darzalex Faspro, pomalidomide, and dexamethasone. J&J said that after a median follow-up of 24.6 months, both Talvey combinations met the primary endpoint; compared with the control therapy, the reduction in the risk of disease progression or death was as high as 72%.

According to the data released by the company, the Tal-DP group with pomalidomide added had a progression-free survival rate of 81.3% at 24 months, the Tal-D group without pomalidomide had a rate of 77.6%, and the control group had a rate of 51.2%. For overall survival, Tal-DP and Tal-D were 89.2% and 87.9%, respectively, at 24 months, compared with 79.1% in the control group; J&J also said the reduction in the risk of death was as high as 53%.

These results have drawn attention because Talvey targets GPRC5D, which differs from the commonly used BCMA target. In theory, this provides another pathway for attacking myeloma cells and may also allow physicians to adjust immunotherapy strategies after patients have undergone treatments such as lenalidomide and proteasome inhibitors. However, the information currently available publicly comes mainly from the company’s press release and conference presentation abstracts, and the full clinical significance still needs to be interpreted in the context of peer-reviewed papers, subsequent regulatory assessments, and real-world clinical use.

Beyond efficacy, safety remains another side of bispecific antibodies that cannot be overlooked. J&J said the overall safety of the Talvey combinations was broadly consistent with the known profiles of the individual drugs; cytokine release syndrome occurred in 67.8% and 58.4% of patients in the Tal-DP and Tal-D groups, respectively, with most events being low grade. Taste changes, weight loss, and balance-related adverse events were also more common. Although most were low grade, they still have practical implications for long-term treatment tolerability and quality of life.

The study enrolled 864 patients, all of whom had previously received lenalidomide and a proteasome inhibitor, and most of whom were already refractory to lenalidomide and their most recent line of therapy. This makes the trial population fairly close to the relapse scenarios commonly seen in current clinical practice, but it also serves as a reminder that the data cannot be directly extrapolated to newly diagnosed patients or those who have not undergone multiple prior treatments.

J&J said it has submitted a supplemental biologics license application to the U.S. FDA and a Type II variation application to the European Medicines Agency, seeking use of Talvey with Darzalex Faspro, with or without pomalidomide, in multiple myeloma that is relapsed or refractory after at least one prior line of treatment. If regulators accept these data, the position of bispecific antibodies in myeloma treatment will no longer be only as a last-line option, but may move earlier into the core of relapse treatment decision-making.