Talquetamab/Teclistamab Combo Shows Promising Efficacy in R/R Multiple Myeloma with EMD

The combination of the bispecific antibodies talquetamab-tgvs (Talvey) and teclistamab-cqyv (Tecvayli) achieved deep and lasting responses in patients with triple-class-exposed relapsed/refractory multiple myeloma (R/R MM) who also had true extramedullary disease (EMD). These findings, from the phase 2 RedirecTT-1 trial (NCT04586426), were presented at the 2025 ASH Annual Meeting & Exposition and published concurrently in the New England Journal of Medicine.^1,2

With a median follow-up of 16.8 months, the overall response rate (ORR) was 79% (95% CI, 69%-87%), with a complete response (CR) or better rate of 53%. Stringent CRs (sCRs) were noted in 44 patients, CRs in 9, very good partial responses (VGPRs) in 17, and PRs in 9. The median time to first response was 2.6 months (range, 1.0-5.8), and the median time to best response was 5.1 months (range, 1.0-16.6). The median duration of response (DOR) was not reached (NR; 95% CI, 11.5-not estimable [NE]), with a 12-month DOR rate of 62.1% (95% CI, 49.0%-72.7%).

Notably, investigators stated that, with an additional approximate 4 months of follow-up, the ORR approached 80%, and that 62% of responders remained in their response at 1 year.

In the study, accurate extramedullary disease assessment by high-sensitivity fluorodeoxyglucose PET-CT utilizing the Deauville scale and International Myeloma Working Group criteria confirmed treatment efficacy and found that a patient remained in CR with talquetamab plus teclistamab. In a chart evaluating this patient’s overall extramedullary disease tumor response and 5-point Deauville scale score, it was reported that at baseline, their tumor response was not applicable, and their Deauville scale score was 5; at day 76, the tumor response was VGPR, and the Deauville scale was 5; at day 167, they were VGPR and 4, respectively; at day 250, they were CR and 1; and at day 419, they were CR and 1.

The ORR among patients with organ extramedullary disease (n = 32) was 78% (95% CI, 60%-91%), with a CR or better rate of 56%; sCRs were reported in 47 patients, CRs in 9, VGPRs in 16, and PRs in 6. Among patients with non-organ extramedullary disease (n = 58), the ORR was 79% (95%, 67%-89%), and the CR or better rate was 52%; sCRs were reported in 43 patients, CRs in 9, VGPRs in 17, and PRs in 10. Additionally, the median DOR was not reached in patients with organ extramedullary disease and 15.4 months in patients with non-organ extramedullary disease.

Organ extramedullary disease included the kidney, liver, lung, and others; non-organ extramedullary disease included lymph node and soft tissue.

Across subgroups, the ORR was 93% (95% CI, 81%-99%) with a CR or better rate of 58% in patients with less than 25 cm² baseline extramedullary disease tumor volume (n = 43); in patients with 25 to 50 cm² baseline extramedullary disease tumor volume (n = 21), the ORR and CR or better rates were 67% (95% CI, 43%-95%) and 57%, respectively; in patients with more than 50 cm² baseline extramedullary disease tumor volume, the rates were 65% (95% CI, 44%-83%) and 42%.

The investigators noted that the highest level of responses was observed in patients with lower baseline volumes, and at higher volumes, responses were generally comparable with the overall population.

Across all patients, the median progression-free survival (PFS) was 15.0 months (95% CI, 10.3-NE), with a 12-month PFS rate of 57.5% (95% CI, 46.4%-67.1%); the median overall survival (OS) was NR (95% CI, 19.7-NE), with a 12-month OS rate of 73.8% (95% CI, 63.3%-81.8%).

During the presentation, the presenting study author Saad Z. Usmani, MD, MBA, FACP, FASCO, myeloma specialist and cellular therapist, and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center, stated, “In summary, deep and durable responses in true [extramedullary disease] and teclistamab plus talquetamab combinations were observed in this experience.”

A total of 90 patients received subcutaneous talquetamab at 0.8 mg/kg every 2 weeks plus subcutaneous teclistamab at 3.0 mg/kg every 2 weeks, with the option to switch to monthly dosing after 4 cycles and a VGPR or better, or 6 cycles irrespective of response. Step-up dosing occurred 2 to 4 days apart and was administered at 3 levels: level 1, at 0.01 mg/kg of talquetamab plus 0.06 mg/kg of teclistamab; level 2, at 0.06 mg/kg plus 0.3 mg/kg, respectively; and level 3, at 0.4 mg/kg plus 1.5 mg/kg.

Eligible patients in the trial had triple-class-exposed relapsed/refractory multiple myeloma and true extramedullary disease, defined as at least 1 nonradiated bone-independent soft tissue plasmacytoma of 2 cm or more in greatest dimension confirmed by central review of PET-CT scans. Additionally, prior CAR-T and non-BCMA/GPRC5D bispecific antibodies, as well as nonsecretory and oligosecretory disease, were permitted.

The median age of patients was 64.5 years, 63.3% were male, and the median number of prior lines of treatment was 4 (range, 1-10).

The primary end point was ORR; secondary end points included DOR, PFS, OS, and safety.

Regarding safety, the most common adverse effects (AEs) of any grade and grade 3 or 4 were oral (86.7% and 4.4%, respectively), infections (80.0% and 33.3%), cytokine release syndrome (CRS; 77.8% and 0.0%), and neutropenia (72.2% and 63.3%). Grade 3 or 4 anemia and thrombocytopenia occurred in 33.3% and 25.6%, respectively.

The new onset of key any-grade AEs was less common when patients switched from dosing every 2 weeks to every 4 weeks, as any-grade infections went from 72.2% to 60.7%, weight decrease went from 51.1% to 26.8%, and oral AEs went from 85.6% to 21.4%.

The most common any-grade infections were upper respiratory tract infection (30.0%), COVID-19 (22.2%), pneumonia (21.1%), and urinary tract infection (13.3%). Observed grade 3 or 4 infections were consistent with reports of teclistamab monotherapy and were mainly limited to the first 6 months of treatment before declining.

Talquetamab or teclistamab were discontinued by 8.9% of patients due to AEs, of whom 6 patients discontinued both agents and 2 patients discontinued only talquetamab. Grade 5 AEs were also reported in 12.2% of patients, with 5.6% being noninfection AEs and 6.7% being infections.

REFERENCES

1.Usmani S, Kumar S, Mateos MV, et al. Efficacy and safety of talquetamab + teclistamab in patients with Relapsed/Refractory multiple myeloma and extramedullary disease: Updated Phase 2 results from the redirectt-1 study with extended follow-up. Blood. 2025;146(supp 1):698. doi:10.1182/blood-2025-698

2.Kumar S, Mateos MV, Ye JC, et al. Dual targeting of extramedullary myeloma with talquetamab and teclistamab. N Engl J Med. Published online December 7, 2025. doi:10.1056/NEJMoa2514752