Bispecific Intensification Yields 73% MRD-Negative CR Rate in High-Risk Newly Diagnosed Myeloma

Adding the bispecific antibody teclistamab (Tecvayli) to daratumumab (Darzalex), both from Janssen Biotech, after standard quadruplet induction sharply deepened responses in patients with newly diagnosed high-risk multiple myeloma, with nearly three-quarters reaching minimal residual disease (MRD)–negative complete response (CR), according to primary end point results from the phase 2 GEM-TECTAL trial (NCT5849610).¹

The data, presented as a late-breaking abstract at the 23rd International Myeloma Society (IMS) Annual Meeting, held September 23-26, 2026, in Glasgow, Scotland, come from a PETHEMA/GEM study in Spain testing whether an MRD-guided, transplant-free strategy built on T-cell redirection can help patients who tend to relapse early despite modern frontline therapy.¹

Study design

GEM-TECTAL enrolled patients with newly diagnosed disease regardless of transplant eligibility who had at least 1 high-risk feature: del(17p), del(1p), t(4;14), t(14;16), or amp(1q) by fluorescence in situ hybridization; Revised International Staging System stage III; or extramedullary or paramedullary disease.^1,2

Patients received 4 cycles of daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRd), followed by 6 cycles of teclistamab-daratumumab (Tec-Dara) intensification. Those who were MRD negative moved to 2 years of Tec-Dara maintenance; those with persistent MRD received early rescue with talquetamab (Talvey; Janssen Biotech) plus daratumumab (Tal-Dara). The Tec-Dara schedule aligns with the regimen FDA approved in March 2026 for relapsed/refractory disease based on the phase 3 MajesTEC-3 trial (NCT05083169); it becomes steroid-free after 2 cycles, with monthly dosing after cycle 6.^1,3,4

The primary end point was MRD-negative CR at 10⁻⁶, with next-generation flow cytometry after intensification.

A very high-risk population

Of 42 patients screened, 30 began induction and formed the intention-to-treat (ITT) population. Median age was 70 years (range, 48-77), with 70% showing high-risk cytogenetic abnormalities—most often amp(1q)—and 70% meeting ultra-high-risk criteria. In addition, one-third had 2 or more high-risk abnormalities. Nearly two-thirds (63.3%) had extramedullary or paramedullary disease, mostly bone plasmacytomas.¹

Responses deepened with intensification

After D-VRd, the overall response rate was 76.7%, 20% of patients had CR or better, and 13.3% had MRD-negative CR. After Tec-Dara intensification, all 28 patients who received it reached at least a very good partial response, and the ITT rate of CR or better climbed to 83.3%.¹

The trial met its primary end point: 73.3% (22 of 30) achieved MRD-negative CR, and 22 of 25 patients in CR (88%) were MRD negative. Patients with missing or nonevaluable samples were counted as MRD positive. At a median follow-up of 9.8 months, 1 patient had switched to Tal-Dara rescue, 22 remained on Tec-Dara maintenance, and 23 remained on study.¹

Safety

Among the 28 patients who received intensification, infections occurred in 78.6%, mostly upper respiratory, and were grade 3 or 4 in 14.3%. There were no fatal infections or teclistamab discontinuations due to infection; 75% of patients received immunoglobulin replacement. Grade 3/4 neutropenia occurred in 39.3%. Cytokine release syndrome occurred in 25%, all grade 1, with a median duration of 1 day; 1 patient received tocilizumab. One patient had grade 2 immune effector cell–associated neurotoxicity syndrome. Two patients (7.1%) stopped teclistamab because of grade 3 rash or grade 3 neuropathy. Two deaths, from pulmonary edema and COVID-19 pneumonia, were reported; investigators reported no treatment-related deaths.¹

What comes next

The investigators concluded that early Tec-Dara intensification within an MRD-guided strategy produced deep responses and high MRD-negative CR rates, supporting further study of a fully immune-based, transplant-free approach for difficult-to-treat high-risk myeloma. Follow-up remains short, and progression-free survival, overall survival, and durability of MRD negativity are secondary objectives yet to be reported.¹

PETHEMA/GEM is conducting the study with financial support from Janssen Pharmaceutica NV, a Johnson & Johnson company.¹

References

1. Rodríguez-Otero P, Ocio EM, Oriol A, et al. MRD-guided frontline T-cell redirection therapy for newly diagnosed high-risk multiple myeloma using teclistamab-daratumumab intensification and talquetamab-daratumumab early rescue intervention: primary endpoint of the phase 2 GEM-TECTAL trial. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.
2. Teclistamab and daratumumab or talquetamab and daratumumab in high-risk newly diagnosed multiple myeloma (GEM-TECTAL). ClinicalTrials.gov identifier: NCT05849610. Accessed October 29, 2026. https://clinicaltrials.gov/study/NCT05849610
3. Mateos MV, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator's choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients (pts) with relapsed refractory multiple myeloma (RRMM): results of MajesTEC-3. Blood. 2025;146(suppl 2):LBA-6. doi:10.1182/blood-2025-LBA-6
4. Johnson & Johnson announces U.S. FDA approval of TECVAYLI plus DARZALEX FASPRO for relapsed/refractory multiple myeloma, offering a potential new standard of care as early as second line. News release. Johnson & Johnson. March 5, 2026. Accessed October 29, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-u-s-fda-approval-of-tecvayli-plus-darzalex-faspro-for-relapsed-refractory-multiple-myeloma-offering-a-potential-new-standard-of-care-as-early-as-second-line