Persistence of Remission Following Discontinuation of BCMA-CD3 Bispecific Antibodies in Multiple Myeloma Patients With Major M-Spike Response

The primary objective of this study is to evaluate the duration of remission and therapy-free interval following the discontinuation of BCMA-CD3 bispecific antibody therapy in patients with multiple myeloma demonstrating a major M-spike response. 5

Secondary objectives include:

• Identification of clinical and biological factors influencing the persistence of remission, such as disease characteristics, prior therapy count, refractoriness, risk score, treatment duration, and pretreatment type.
• Estimation of overall survival, progression-free survival, and the probability of early therapy re-initiation without prior relapse according to IMWG criteria.
• Assessment of patient-reported quality of life, symptom burden, and the incidence of infections.
• Evaluation of the medico-economic impact of treatment discontinuation.

The sponsor did not provide information regarding the total number of participants. The study population consists of adults, aged 18 years or older, of both genders diagnosed with multiple myeloma according to IMWG criteria. Eligible subjects are currently receiving BCMA-CD3 bispecific antibody therapy and have achieved a biochemical complete response characterized by an unmeasurable M-spike and normal or unmeasurable free light chains. Participants must have had measurable disease prior to the initiation of the current bispecific antibody treatment, specifically defined as an M-spike greater than 5g/L or involved free light chains exceeding 100mg/L. Inclusion requires the availability of baseline data from the initial diagnosis and records of prior therapeutic interventions.

This multicenter, prospective, phase II trial is designed to estimate the persistence of remission following the discontinuation of BCMA-CD3 bispecific antibody therapy in patients with multiple myeloma who have achieved a major M-spike response. The study focuses on assessing disease free survival as the primary endpoint, evaluated at 6 months and 3 years. Secondary endpoints include overall survival, progression-free survival, the incidence of clinical relapse, and the proportion of patients achieving a new response upon therapy re-initiation. Safety assessments will monitor the incidence and severity of adverse events, specifically infection rates, while economic analyses will evaluate healthcare utilization. Additionally, patient-reported outcomes via quality of life measures and exploratory biomarker analyses will be conducted. The study involves a sequence of assessments starting from a screening phase to confirm biochemical complete response and measurable disease history, followed by monitoring after the cessation of elranatamab or teclistamab. The total trial duration is estimated to extend from March 2026 to March 2031.

The experimental treatment involves the administration of elranatamab, provided as ELREXFIO in a solution for injection. This BCMA-CD3 bispecific antibody is administered via subcutaneous injection.

The experimental treatment also includes teclistamab, provided as TECVAYLI in a solution for injection. This agent is administered via subcutaneous injection at a dose of 90 mg/kg.

The assessment of efficacy in patients with multiple myeloma focuses on the duration of remission and therapy-free time following the discontinuation of BCMA-CD3 bispecific antibody therapy. The primary endpoint is disease-free survival, which is determined based on sustained major myeloma response at 6 months and 3 years.

Secondary efficacy parameters include:

• Overall survival and progression-free survival.
• The incidence of major myeloma response loss and clinical relapse, as defined by IMWG criteria, at 6 months and 3 years, including the median time to both events.
• The proportion of patients achieving a new major myeloma response upon the re-initiation of therapy.
• Changes from baseline in quality of life and symptom burden, measured using the EQ-5D instrument at serial time points.
• Exploratory analyses of baseline factors, such as cytogenetic risk and the depth of initial response, in relation to the risk of molecular relapse and the durability of treatment-free remission.