Phase 3 Randomized Trial of Teclistamab + Talquetamab Combination vs Daratumumab + Lenalidomide Maintenance in MRD‑Positive Newly Diagnosed Multiple Myeloma Post‑ASCT

Primary objective: to compare Tec‑Tal maintenance with daratumumab‑lenalidomide maintenance for achieving MRD‑negative (10⁻⁵) complete response at 12 months in patients with newly diagnosed multiple myeloma who remain MRD‑positive after autologous stem‑cell transplantation. Secondary objectives:

• evaluation of progression‑free survival, CR or better, and PFS2;
• assessment of overall survival;
• comparison of overall safety profile between the two maintenance regimens;
• determination of MRD negativity (10⁻⁵) at any timepoint;
• evaluation of sustained MRD negativity (10⁻⁵);
• analysis of patient‑reported outcomes.

The trial enrolled adult patients (≥18 years) of both sexes diagnosed with Multiple myeloma according to International Myeloma Working Group criteria, who had completed a single or tandem autologous stem cell transplantation following standard induction therapy that included an anti‑CD38 antibody, an immunomodulatory drug, and a proteasome inhibitor. Eligible participants demonstrated measurable residual disease in the bone marrow at a sensitivity of 10⁻⁵ after transplantation and were within the protocol‑defined post‑transplant time window, with or without consolidation therapy. Inclusion required an adequate performance status (Karnofsky ≥50 % or ECOG ≤2) and sufficient hematologic, renal, hepatic, and calcium parameters, as well as compliance with contraceptive requirements when applicable. Both female and male patients, including vulnerable individuals, were considered. No specific lifestyle restrictions such as diet or physical activity were stipulated in the available data. The sponsor did not provide information on the total number of participants enrolled in the study.

The study is a phase 3 randomized controlled trial comparing a maintenance regimen of teclistamab and talquetamab (Tec‑Tal) with daratumumab plus lenalidomide (DR) in patients with multiple myeloma who remain minimal residual disease positive after autologous hematopoietic stem cell transplantation. Eligible adults (≥18 years) with documented disease, MRD positivity at a sensitivity of 10⁻⁵, and adequate organ function are screened, consented, and undergo a baseline (screening) visit to confirm eligibility. After randomization, participants receive subcutaneous administrations of either the investigational bispecific antibodies (teclistamab and talquetamab) or the comparator daratumumab, together with oral lenalidomide as background therapy. Study visits are scheduled at regular intervals (e.g., monthly) to assess safety, pharmacologic exposure, and efficacy, including MRD status and response criteria; a definitive end‑of‑study visit occurs at month 12 to evaluate the primary endpoint of MRD‑negative complete response. Participant involvement therefore extends for at least 12 months, with additional follow‑up as required by protocol. Early termination may occur for disease progression, unacceptable adverse events, withdrawal of consent, or significant protocol deviations.

The investigational arm includes talquetamab, supplied as a solution for injection for subcutaneous use. The dose is weight‑based, expressed in micrograms per kilogram, and is administered subcutaneously according to the protocol‑defined dosing schedule. The formulation is a sterile aqueous solution intended for injection, and dosing intervals are recorded in the study treatment log to ensure compliance.

The second experimental agent, teclistamab, is also provided as a solution for injection for subcutaneous administration. Dosing is weight‑based in milligrams per kilogram and follows the schedule specified in the study protocol. Each administration is documented, and participants are monitored for adherence through site‑based dosing records and patient diaries.

The comparator regimen consists of daratumumab 1800 mg administered as a subcutaneous injection of a solution for injection. The fixed dose is given per the approved prescribing information and the study’s dosing schedule, with each administration recorded in the trial database to verify compliance.

All participants receive background therapy with oral lenalidomide 15 mg hard capsules. The medication is taken daily in accordance with the study protocol, and pill counts together with patient self‑reporting are employed to monitor adherence.

The primary efficacy assessment is MRD‑CR negativity (10⁻⁵) with complete response at Month 12. Patients will undergo MRD testing at a sensitivity of 10⁻⁵ and evaluation for complete response at the 12‑month visit, using a validated assay on bone‑marrow specimens collected according to the study schedule.

Secondary efficacy parameters include Progression‑free survival, Complete response or better, PFS2 (progression‑free survival to second disease progression or death), Overall survival, MRD negativity (10⁻⁵), sustained MRD negativity (10⁻⁵) for at least 12 months, time to worsening of symptoms, and the mean change from baseline in the EORTC QLQ‑C30 global health status and functional scale scores (including MY‑20). These endpoints will be measured at predefined timepoints throughout the follow‑up period, with survival outcomes calculated from the date of randomization to the occurrence of the respective event.