The CHMP recommends TALVEY plus daratumumab, with or without pomalidomide, for earlier-line multiple myeloma after Phase 3 MonumenTAL-3 results showed improved progression-free survival.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
Johnson & Johnson announced on October 16, 2026, that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended extending the indication for TALVEY® (talquetamab) in combination with daratumumab, with or without pomalidomide, for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one previous line of therapy.
If approved by the European Commission, the expanded indication could provide an additional treatment option as early as second line. The recommendation is based on Phase 3 MonumenTAL-3 findings showing improved disease control with both talquetamab-containing regimens compared with daratumumab, pomalidomide and dexamethasone (DPd).
MonumenTAL-3: Clinical Evidence
MonumenTAL-3 (NCT05455320) is an ongoing, randomised Phase 3 trial involving 864 patients with RRMM who had received at least one previous line of therapy and had been exposed to lenalidomide and a proteasome inhibitor. Participants were assigned to talquetamab plus daratumumab (Tal-D), talquetamab plus daratumumab and pomalidomide (Tal-DP), or DPd.
The primary endpoint was progression-free survival (PFS), which measures the time patients remain alive without disease progression. Key secondary endpoints included overall response rate (ORR), complete response or better, measurable residual disease (MRD)-negative complete response, overall survival (OS) and safety.
Improved Disease Control and Response Depth
At a median follow-up of 24.6 months, both talquetamab-containing regimens significantly improved PFS compared with DPd. The hazard ratio was 0.28 for Tal-DP and 0.33 for Tal-D, corresponding to relative reductions of 72% and 67%, respectively, in the risk of disease progression or death. Estimated 24-month PFS rates were 81.3% with Tal-DP and 77.6% with Tal-D, compared with 51.2% with DPd.
ORR was 88.2% with Tal-DP, 88.5% with Tal-D and 77.6% with DPd. Complete response or better was achieved in 71.1%, 68.9% and 34.5%, respectively. MRD-negative complete response or better, assessed at the 10⁻⁵ threshold, was reported in 52.3%, 46.3% and 15.9%, respectively.
These findings support deeper responses and better disease control with both talquetamab combinations than with DPd. However, the similar ORRs for Tal-DP and Tal-D do not establish an additional response benefit from including pomalidomide. The reported comparisons were against DPd, not direct tests of superiority between the two talquetamab regimens.
Overall Survival and Safety
At 24 months, estimated OS rates were 89.2% with Tal-DP, 87.9% with Tal-D and 79.1% with DPd. The hazard ratios for death versus DPd were 0.47 for Tal-DP and 0.51 for Tal-D, indicating lower observed risks of death in both experimental groups.
However, the OS findings require statistical qualification. Although the nominal p-values were 0.0006 for Tal-DP and 0.0015 for Tal-D, neither comparison crossed the prespecified interim-analysis boundary of p=0.0001 for declaring OS superiority. The results therefore favour both combinations but do not establish formal OS superiority at this analysis.
Safety remains an important consideration. Grade 3 or 4 treatment-emergent adverse events occurred in 94.9% of patients receiving Tal-DP, 74.8% receiving Tal-D and 91.5% receiving DPd. Infections occurred in 87.3%, 84.3% and 83.0%, respectively, while grade 3 or 4 infections occurred in 37.7%, 29.2% and 42.2%. Adverse events led to treatment discontinuation in 10.5% of Tal-DP patients, 8.0% of Tal-D patients and 6.7% of DPd patients.
Serious adverse events occurred in 63.0% of patients receiving Tal-DP, 52.6% receiving Tal-D and 53.7% receiving DPd. These findings highlight the need to assess the efficacy of each regimen alongside its adverse-event burden.
Mechanism of Action
Talquetamab is a bispecific T-cell-engaging antibody that binds GPRC5D on multiple myeloma cells and CD3 on T cells, bringing immune cells into contact with malignant cells. Daratumumab targets CD38, providing a complementary mechanism, while pomalidomide is an immunomodulatory agent included in the Tal-DP regimen.
Clinical Interpretation
MonumenTAL-3 provides Phase 3 evidence supporting talquetamab plus daratumumab, with or without pomalidomide, as a potential earlier-line treatment option for RRMM. Both combinations improved PFS and response measures compared with DPd, while the OS estimates are encouraging but require the qualification imposed by the prespecified interim-analysis boundary.
The safety findings also matter when considering treatment selection. Tal-D had numerically lower rates of grade 3 or 4 treatment-emergent adverse events and severe infections than Tal-DP, but the trial comparisons presented here do not establish that one talquetamab regimen has a superior overall benefit-risk profile. The CHMP recommendation marks a regulatory milestone; the expanded indication remains subject to the European Commission’s decision.
References
CHMP recommends approval of Johnson & Johnson’s TALVEY®▼ (talquetamab) plus daratumumab in earlier line treatment of relapsed/refractory multiple myeloma, Johnson and Johnson, 16 October 2026
A Study Comparing Talquetamab in Combination with Daratumumab or in Combination with Daratumumab and Pomalidomide Versus Daratumumab in Combination with Pomalidomide and Dexamethasone in Participants with Multiple Myeloma That Returns After Treatment or is Resistant to Treatment (MonumenTAL-3), ClinicalTrials.gov ID NCT05455320
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.