New Myeloma Combo Cuts Risk of Relapse by Up to 72% — Here's What It Could Mean for You

A new two- or three-drug combination is helping patients with relapsed multiple myeloma go significantly longer without their cancer coming back — and it could be used as early as the first relapse.

A large randomized trial has found that combining Talvey (talquetamab) with Darzalex (daratumumab), with or without Pomalyst (pomalidomide), significantly lowered the risk of disease progression or death compared with a standard three-drug regimen in patients with relapsed or refractory multiple myeloma.

The progression-free survival and response-rate results were first presented at the European Hematology Association (EHA) 2026 Congress on June 13, 2026. More recently, Johnson & Johnson previewed additional overall survival findings ahead of the International Myeloma Society (IMS) 2026 Annual Meeting, where the full survival data are expected to be presented in detail September 23–26, 2026, in Glasgow, Scotland. Researchers say the findings so far support using Talvey (talquetamab)-based combinations earlier in treatment — potentially as soon as a patient's disease returns after just one prior line of therapy.

What the trial tested

MonumenTAL-3 enrolled 864 patients with relapsed or refractory multiple myeloma who had already been treated with a proteasome inhibitor and Revlimid (lenalidomide) and had gone through at least one prior line of therapy. Patients were assigned to one of three groups:

• Tal-DP: Talvey (talquetamab) plus Darzalex (daratumumab) and Pomalyst (pomalidomide)
• Tal-D: Talvey (talquetamab) plus Darzalex (daratumumab), no Pomalyst (pomalidomide)
• DPd (control): Darzalex (daratumumab), Pomalyst (pomalidomide), and dexamethasone — a standard-of-care regimen

Talvey (talquetamab) and Darzalex (daratumumab) work in different ways. Talvey (talquetamab) is a bispecific antibody that latches onto a protein called GPRC5D on myeloma cells and onto CD3 on T cells, effectively steering the immune system's T cells toward the cancer. Darzalex (daratumumab) is a monoclonal antibody that targets CD38, another protein commonly found on myeloma cells.

Fewer patients saw their cancer progress

After a median follow-up of roughly two years, both Talvey (talquetamab)-containing combinations outperformed the standard regimen on progression-free survival — the length of time patients lived without their myeloma getting worse.

• The three-drug Tal-DP combination cut the risk of progression or death by 72% compared with the control regimen.
• The two-drug Tal-D combination cut that risk by 67%.
• At 24 months, 81.3% of patients on Tal-DP and 77.6% of patients on Tal-D had not progressed, compared with roughly half of patients on the standard regimen.

Investigators have also reported, in a preview ahead of the IMS 2026 meeting, that both Talvey (talquetamab) combinations improved overall survival compared with the standard regimen — reducing the risk of death by about half, with two-year survival rates favoring the Talvey (talquetamab)-based groups. Those figures come from a pre-conference company announcement rather than a full presentation, so some details may be refined when the complete data are presented at IMS 2026 later this month. The progression-free survival benefit — which was presented in full at EHA — held up across different patient subgroups, including those with higher-risk disease features.

Responses were also deeper with the Talvey (talquetamab) combinations: more than two-thirds of patients receiving either regimen reached a complete response or better, compared with roughly a third of patients on the standard regimen, and a substantially larger share had no detectable trace of disease using a sensitive minimal residual disease (MRD) test.

"Synergistic Talvey (talquetamab)-Darzalex (daratumumab)-based immunotherapy combinations significantly improved progression-free survival, with clear benefit across clinically relevant subgroups," said Dr. Peter M. Voorhees of Atrium Health Levine Cancer Institute and Wake Forest University School of Medicine, who presented the data. He added that the results support using Talvey (talquetamab) plus Darzalex (daratumumab), with or without Pomalyst (pomalidomide), "as a new standard of care" for relapsed or refractory myeloma as early as the first relapse.

Side effects patients should know about

Talvey (talquetamab) and Darzalex (daratumumab) don't work like traditional chemotherapy, so they don't cause the same side effects. Here's what to expect in plain terms:

• Flu-like symptoms soon after a dose. This is called cytokine release syndrome, or CRS for short. It happens when the immune system revs up quickly and can cause fever, chills, or a drop in blood pressure. It's common with Talvey (talquetamab), but in this trial most cases were mild and manageable, usually showing up shortly after a dose rather than persisting.
• Confusion or nerve-related symptoms (uncommon). Doctors call this ICANS. It's a known risk with drugs like Talvey (talquetamab) that engage T cells, but in this trial it was rare.
• Changes in taste, skin, and nails. This is specific to Talvey (talquetamab) because of the particular protein it targets, which also happens to sit on taste buds, skin, and nail cells. Patients may notice food tasting different or bland, along with skin or nail changes.
• Weight loss. Some patients lost weight while on Talvey (talquetamab), most often those who started treatment overweight. Patients who began at a healthy or lower weight generally stayed stable — so this side effect wasn't universal.
• Higher infection risk with Pomalyst (pomalidomide). The regimens that included Pomalyst (pomalidomide) — Tal-DP and the standard-of-care arm — had more low white blood cell counts (neutropenia) and more serious infections than the Talvey (talquetamab)-Darzalex (daratumumab) combination without Pomalyst (pomalidomide). This is a tradeoff worth discussing with your doctor: adding the third drug may boost effectiveness but also raises infection risk.

Bottom line for patients: the taste, skin, and weight changes are the most distinctive side effects of this combination — different from what many patients expect from cancer treatment — so it's worth asking your care team what to watch for and how to manage them early, rather than waiting until they become bothersome.

What this could mean for patients

Multiple myeloma almost always returns after initial treatment, and patients often need several different regimens over time as their disease develops resistance. MonumenTAL-3 was designed to test whether moving a Talvey (talquetamab)-based combination earlier in the treatment sequence — right after a patient's first relapse — could keep the disease under control longer than currently used regimens.

Both Talvey (talquetamab) and Darzalex (daratumumab) are already individually approved for use in multiple myeloma, including in other combinations, so this trial is testing a new way of combining existing approved drugs rather than an entirely new medicine. As of this writing, this specific triplet/doublet combination for early relapse has not received FDA approval; the data have been presented at medical conferences and are still working through the regulatory and publication process. Patients should ask their oncologist whether this approach is available to them, including through a clinical trial, and how it might compare with other options for their specific situation.

Editor's note: Progression-free survival and response data were presented at EHA 2026. Overall survival data reflect a company preview ahead of the IMS 2026 Annual Meeting, where complete results are expected. These figures may be refined after the full analysis. This combination is investigational for this use and is not FDA approved. Patients should speak with their oncologist about treatment options, including clinical trials.

References

1. International Myeloma Foundation. "Results from Phase 3 MonumenTAL-3 Study at EHA 2026: Talquetamab Plus Daratumumab Showed Significant Reduction in Risk of Disease Progression in Relapsed/Refractory Myeloma." June 18, 2026. https://www.myeloma.org/news-events/multiple-myeloma-news/monumental-3-study-results-eha-2026
2. BioPharma International. "Talquetamab-Daratumumab Combination Reduces Progression Risk 72% in Phase 3 Relapsed Multiple Myeloma Trial." https://www.biopharminternational.com/view/talquetamab-daratumumab-combination-reduces-progression-risk-72-phase-3-relapsed-multiple-myeloma-trial
3. ClinicalTrials.gov. MonumenTAL-3 (NCT05455320): A Study Comparing Talquetamab Subcutaneous (SC) Combinations Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) in Participants With Relapsed/Refractory Multiple Myeloma.

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