Systemic light-chain (AL) amyloidosis is a plasma cell disorder characterized by the production of misfolded immunoglobulin light chains that deposit in organs and lead to progressive organ dysfunction. Although daratumumab-based therapy has improved outcomes, a substantial proportion of patients fail to achieve deep hematologic responses. This is a prospective, single-arm, single-center clinical study evaluating the safety and efficacy of the BCMA/GPRC5D/CD3 trispecific antibody QLS4131 in patients with newly diagnosed systemic AL amyloidosis.
Systemic light-chain (AL) amyloidosis is a rare plasma cell disorder caused by the production of monoclonal immunoglobulin light chains that misfold and deposit in vital organs, resulting in progressive organ dysfunction and poor survival. Rapid suppression of pathogenic plasma cells and achievement of deep hematologic responses are strongly associated with improved organ recovery and survival. Current first-line treatment based on daratumumab plus cyclophosphamide, bortezomib, and dexamethasone has significantly improved clinical outcomes; however, approximately 40% of patients do not achieve complete hematologic remission, and early mortality remains substantial. Therefore, more effective frontline therapies are needed. QLS4131 is a novel GPRC5D/BCMA/CD3 trispecific antibody that simultaneously targets two plasma-cell antigens (BCMA and GPRC5D) while redirecting CD3-positive T cells to eliminate malignant plasma cells. Dual-antigen targeting may improve tumor recognition, reduce antigen escape, and enhance antitumor activity without substantially increasing toxicity. This prospective, single-arm, single-center study will enroll approximately 20 adult patients with newly diagnosed systemic AL amyloidosis. Participants will receive subcutaneous QLS4131 using a step-up dosing schedule followed by maintenance dosing for 6 to 8 treatment cycles.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
QLS4131 is an investigational GPRC5D/BCMA/CD3 trispecific antibody administered by subcutaneous injection. The study uses a step-up dosing schedule followed by full-dose maintenance treatment over 6 to 8 treatment cycles. Supportive care and prophylactic medications for cytokine release syndrome (CRS) are permitted according to the study protocol.
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, China
Hematologic Complete Response (CR) Rate
Proportion of participants achieving hematologic complete response (CR) according to the International Society of Amyloidosis (ISA) response criteria following treatment with QLS4131.
Time frame: At the end of each 28-day treatment cycle and before the start of the next cycle, through Cycle 8 (each cycle is 28 days)
time to hematologic response
Time from the first dose of QLS4131 to the first documented hematologic response.
Time frame: From the first dose until the first documented response, assessed every 2 weeks in Cycle 1 and every 28 days from Cycle 2 through end of treatment (each cycle is 28 days)
Duration of Hematologic Response (DOR)
Time from first observed hematologic response to disease progression or death due to disease progression, whichever occurs first.
Time frame: From first documented response until disease progression or death, assessed up to 2 years
Overall Hematologic Response Rate (ORR)
Proportion of patients achieving a hematologic response of partial response (PR) or better.
Time frame: From first dose through end of treatment, assessed every 28 days
Minimal residual disease (MRD) negativity rate
Proportion of patients achieving bone marrow MRD negativity at a sensitivity of 10-⁵.
Time frame: Bone marrow MRD assessed at the time of suspected hematologic complete response (CR) or dFLC <10 mg/L, up to the end of treatment from first dose
Progression-Free Survival (PFS)
Time from start of treatment to hematologic progression or death, whichever occurs first.
Time frame: From first dose until disease progression or death, assessed up to 2 years
overall survival (OS)
Time from start of treatment to death from any cause.
Time frame: From first dose until death from any cause, assessed up to 2 years
organ response
Organ response rate and time to organ response in patients with baseline organ involvement
Time frame: From first dose through end of follow-up, up to 2 years.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.