TALVEY plus DARZALEX FASPRO data highlights the strength of a bispecific combination in earlier-line relapsed or refractory multiple myeloma

Johnson and Johnson has shared results from the investigational Phase 3 MonumenTAL-3 study, which found that TALVEY, a GPRC5D bispecific antibody, combined with DARZALEX FASPRO with or without pomalidomide, cut the risk of disease progression or death by as much as 72% and reduced the risk of death by up to 53%, when measured against the standard regimen of DARZALEX FASPRO, pomalidomide, and dexamethasone, in patients living with relapsed or refractory multiple myeloma. At 24 months, progression-free survival reached as high as 81.3% compared to 51.2% with standard of care, while overall survival climbed to 89.2% against 79.1%.

This marks the first Phase 3 study to show superior progression-free survival with a GPRC5D bispecific antibody combination earlier in the multiple myeloma treatment course, pointing to the potential for bispecific combinations to move up the treatment paradigm. The findings were presented at the 2026 European Hematology Association Annual Meeting, with simultaneous publication in The New England Journal of Medicine.

“The impressive results from this study point to the promise of TALVEY plus DARZALEX FASPRO as a potential new bispecific combination for patients with relapsed or refractory multiple myeloma,” said Peter Voorhees, M.D., Professor of Hematology and Oncology at Atrium Health, Levine Cancer Institute at Wake Forest University School of Medicine. “TALVEY works with DARZALEX FASPRO in earlier lines, a critical time for treating patients with the most effective regimens.”

“The MonumenTAL-3 findings underscore our commitment to bringing bispecific combinations into earlier lines of therapy, building on the strength and breadth of Johnson and Johnson’s multiple myeloma portfolio,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Head, Oncology, Johnson and Johnson. “These results add to our growing body of evidence across bispecific antibodies and reinforce our strategy of advancing differentiated immunotherapies to better match the right therapy to the right patient at each stage of disease.”

TALVEY targets GPRC5D, a protein found on multiple myeloma cells as well as certain healthy cells throughout the body. Its expression operates independently of other targets such as BCMA, and it is either absent or present only at low levels on normal B cells, allowing TALVEY to act against myeloma cells while largely leaving healthy B cells untouched.

The MonumenTAL-3 study compared TALVEY paired with DARZALEX FASPRO, and TALVEY paired with DARZALEX FASPRO and pomalidomide, against the standard DPd regimen in patients with relapsed or refractory multiple myeloma who had received at least one prior line of therapy. After a median follow up of two years, both combination arms showed significant gains in progression-free survival relative to DPd, with the triplet combination reaching a 24-month progression-free survival rate of 81.3% and the doublet reaching 77.6%. The 864 enrolled participants had all previously received lenalidomide and a proteasome inhibitor following at least one prior treatment line, with the large majority refractory to lenalidomide and to their most recent therapy, and a smaller subset previously exposed to an anti-CD38 antibody.

Both TALVEY-containing combinations also produced statistically significant improvements over DPd across several key secondary measures, including overall response rate, complete response or better, and minimal residual disease negative complete response or better. After two years of median follow up, overall response rates, complete response rates, and minimal residual disease negative complete response rates all came in markedly higher for both combination arms than for DPd. Overall survival likewise improved meaningfully with both combinations relative to DPd, with the triplet reaching an 89.2% survival rate at 24 months and the doublet reaching 87.9%.

Safety findings across the TALVEY plus DARZALEX FASPRO arms aligned with what has already been established for each therapy individually, and the doublet arm showed a lower incidence of severe infections compared to standard of care. Rates of grade 3 or 4 treatment-emergent adverse events were broadly similar across all three arms. Infection rates were comparable as well, though when narrowed to severe infections specifically, the doublet arm recorded the lowest rate, followed by the triplet arm and then DPd. Grade 5 adverse events occurred infrequently across the study population, with the triplet arm seeing the fewest cases. Treatment discontinuations linked to adverse events occurred in a modest share of patients across all arms, and by the data cutoff, a considerably higher proportion of patients remained on treatment in the combination arms compared to DPd. Cytokine release syndrome was common in both combination arms but was overwhelmingly low grade, while immune effector cell associated neurotoxicity syndrome occurred rarely and without any severe cases reported.

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Related Topics and Keywords

DARZALEX FASPRO®, multiple myeloma, myeloma, refractory multiple myeloma, talvey