Randomized Phase II Study of Teclistamab + Daratumumab‑Lenalidomide‑Dexamethasone (Tec‑DRd) vs Daratumumab‑Lenalidomide‑Dexamethasone (DVRd) in Transplant‑Eligible NDMM

The primary objective is to evaluate the efficacy of the Tec‑DRd regimen versus the standard DVRd regimen by assessing MRD negativity at a sensitivity of 10⁻⁶ after six cycles of induction/consolidation, high‑dose melphalan, and autologous stem cell transplantation, prior to maintenance therapy in transplant‑eligible patients with newly diagnosed multiple myeloma; this endpoint reflects depth of response, a recognized predictor of long‑term disease control. Secondary objectives include:

• Determination of the cumulative sustained (≥12 months) MRD negativity rate (10⁻⁶) by 24 months of maintenance therapy with Tec‑D compared with standard of care maintenance.
• Assessment of the relationship between the duration of Tec‑D maintenance and the cumulative incidence of events of special relevance relative to standard maintenance.

The trial enrolled adult patients aged 18 to 70 years, inclusive, of both sexes, who were diagnosed with transplant‑eligible newly diagnosed Multiple Myeloma according to International Myeloma Working Group criteria and exhibited measurable disease (serum M‑protein ≥1.0 g/dL, urine M‑protein ≥200 mg/24 h, or serum free light chain ≥10 mg/dL with an abnormal kappa/lambda ratio). Participants were required to have an ECOG performance status of 0–2, adequate hematologic, hepatic, renal, and calcium laboratory values, and to be eligible for high‑dose melphalan followed by autologous stem cell transplantation as assessed by the investigator. Selection was based on meeting these clinical and laboratory eligibility parameters, providing informed consent, and adhering to protocol‑specified lifestyle restrictions, which included abstaining from blood donation while receiving lenalidomide and for 28 days thereafter, male participants agreeing not to donate sperm during the study and for three months after the last dose (with consideration of sperm preservation), and all participants complying with contraception requirements and, for females of childbearing potential, negative pregnancy tests. The sponsor did not provide information regarding the total number of participants enrolled.

The study is a phase 5, randomized, double‑blind, active‑controlled trial evaluating Tec‑DRd versus DVRd in transplant‑eligible patients with Multiple Myeloma. Participants undergo a screening visit to confirm eligibility, followed by a baseline visit where the first dose is administered. Induction and consolidation therapy consist of six 28‑day cycles with study drugs given subcutaneously or orally as specified, after which high‑dose melphalan and autologous stem‑cell transplantation are performed. Post‑transplant, participants enter a maintenance phase with scheduled visits every 12 weeks for up to 24 months. The end‑of‑study visit occurs after the maintenance period or earlier if discontinuation criteria are met. Overall participant involvement is approximately 30 months, including screening, treatment, and follow‑up. Early termination may occur due to disease progression, grade 3‑4 adverse events, withdrawal of consent, or investigator decision based on safety concerns.

The investigational product teclistamab is supplied as a solution for injection intended for subcutaneous administration at a dose of 3 mg/kg. The medication is administered according to the study schedule during each treatment cycle, and dosing is recorded in the investigational product log to ensure adherence.

Lenalidomide is provided as hard capsules in strengths of 5 mg, 10 mg, 15 mg, and 25 mg for oral use. Each capsule contains 25 mg of the active substance and is taken according to the protocol‑defined schedule. Capsule counts are performed at each visit to monitor compliance.

Bortezomib is supplied as VELCADE 3.5 mg powder for solution for injection and is administered subcutaneously at a dose of 1.3 mg/m². Injections are given on the days specified in the protocol, and administration details are captured in the injection record.

Daratumumab is supplied as a 1800 mg solution for subcutaneous injection. The fixed dose of 1800 mg is administered per the study schedule, with injection sites and timing documented to verify proper delivery.

Dexamethasone acetate is provided for oral use at a dose of 40 mg. The tablet is taken according to the dosing calendar outlined in the protocol, and patient diaries are used to track intake.

Efficacy will be evaluated primarily by determining the cumulative MRD negativity rate using next‑generation sequencing (NGS) at a sensitivity of 10⁻⁶. Assessment is performed after completion of six cycles of induction/consolidation therapy, high‑dose melphalan, and autologous stem cell transplantation, and prior to the initiation of maintenance treatment.

Secondary efficacy assessments include the sustained MRD‑negative complete response (CR) rate, defined as MRD negativity at 10⁻⁶ by NGS maintained for at least 12 months, evaluated up to 24 months of maintenance therapy. Additionally, a composite endpoint measuring the cumulative rate of clinically relevant events—grade 3 or grade 4 infections, treatment pauses exceeding 62 days, death, disease progression, or discontinuation of all study treatments—is calculated per patient per month of therapy over the 24‑month maintenance period.