Talquetamab (Talvey) Improves Survival for Relapsed/Refractory Multiple Myeloma Earlier in Treatment

People with relapsed/refractory multiple myeloma treated with a combination of talquetamab (Talvey, Johnson & Johnson) and daratumumab (Darzalex Faspro, Johnson & Johnson), with or without pomalidomide (Pomalyst), had lower risk of cancer progression and death compared to those treated with the standard of care. The results of the phase 3 MonumenTAL-3 clinical trial were presented at the 2026 European Hematology Association Congress on June 13. 

“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. Talvey works with Darzalex Faspro in earlier lines—a critical time for patients with the most effective regimens,” said Dr. Peter Vorhees, MD, Professor of Hematology and Oncology at Wake Forest University School of Medicine. 

About talquetamab and daratumumab for multiple myeloma

Talquetamab is a bispecific antibody. Bispecific antibodies are a type of immunotherapy. They attach to both a target on the myeloma cells and a target on cancer-fighting T cells. This brings the T cells closer so it can destroy the myeloma cell. Talquetamab attaches to a protein called GPRC5D.

Talquetamab has been approved since 2023 to treat adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Daratumumab is a monoclonal antibody that targets CD38. It is approved in several different combinations with different indications in newly diagnosed and relapsed/refractory multiple myeloma. 

In the MonumenTAL-3 clinical trial, researchers wanted to know if talquetamab could be given in earlier lines of therapy in combination with daratumumab. 

The MonumenTAL-3 clinical trial

The phase 3 MonumenTAL-3 clinical trial (NCT05455320 enrolled 864 people with relapsed or refractory multiple myeloma. All participants had been treated with at least one prior line of therapy.

They were randomized 1:1:1 to receive one of three therapy combinations:

• Talquetamab plus daratumumab and pomalidomide (Tal-DP)
• Talquetamab plus daratumumab (Tal-D)
• Or standard-of-care daratumumab plus pomalidomide and dexamethasone (DPd)

At the median follow-up of 24.6 months, progression-free survival was significantly higher in both talquetamab groups compared to DPd. Patients treated with Tal-DP had 72% lower risk of death or disease progression compared to DPd. And those treated with Tal-D had a 67% lower risk of death or disease progression compared to DPd.

The overall response rate, complete response rate, and measurable residual disease (MRD)-negative complete response rates were higher in both talquetamab groups compared to the group treated without talquetamab. 

• Overall response rate: 88.2% in Tal-DP and 88.5% in Tal-D vs 77.6% in DPd
• Complete response or better: 71.1% in Tal-DP and 68.9% in Tal-D vs. 34.5% in DPd
• MRD-negative complete response: 52.3% in Tal-DP and 46.3% in Tal-D vs. 15.9% in DPd
  

Rates of severe treatment-related side effects were similar between all three groups. The rate was 94.9% in the Tal-DP group, 74.8% in the Tal-D group, and 91.5% in the DPd group. People treated with Tal-D had the lowest rates of severe infections at 29.2%. The infection rate in the Tal-DP group was 37.7% and 42.2% in the DPd group. Patients in all three groups stopped treatment due to adverse events: 

• 10.5% in the Tal-DP group
• 8% in the Tal-D group
• 6.7% in the DPd group

At data cutoff, 7 out of 10 patients remained on the study treatment in both talquetamab groups, while almost 5 out of 10 remained on the treatment without talquetamab.

What’s next for talquetamab

Based on the results of this clinical trial, Johnson & Johnson is working with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to pursue an approval for this combination.

Sources:

PHASE 3, RANDOMIZED STUDY OF TALQUETAMAB (TAL) PLUS DARATUMUMAB (DARA) ± POMALIDOMIDE (POM) VS DARA PLUS POM AND DEXAMETHASONE (DPD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): MONUMENTAL-3

New TALVEY® (talquetamab-tgvs) plus DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) data demonstrate the strength of a bispecific combination in earlier-line relapsed or refractory multiple myeloma

Talquetamab–Daratumumab in Relapsed or Refractory Myeloma