A Study of Anti-BCMA CAR-T Therapy in Newly Diagnosed Myeloma Patients Who Are Transplant-ineligible

A Multicenter, Open-label, Single-arm Clinical Study of Anti-BCMA CAR-T Cell Therapy in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma

This is a prospective study of anti-BCMA CAR-T in transplant-ineligible patients with newly diagnosed multiple myeloma.

After the diagnosis of multiple myeloma (MM), patients were stratified by frailty status. Frail patients received 4 cycles of VRd regimen (bortezomib, lenalidomide, and dexamethasone), while non-frail patients received 4 cycles of DVRd regimen (daratumumab, bortezomib, lenalidomide, and dexamethasone). Following induction therapy, peripheral blood lymphocytes were collected to manufacture anti-BCMA CAR-T cells. After lymphodepletion with the FC regimen (fludarabine and cyclophosphamide), patients received a single infusion of anti-BCMA CAR-T cells at a target dose of 2.0 × 10^6 CAR-positive cells per kilogram of body weight. Peripheral blood samples were collected at regular intervals to assess treatment efficacy, safety, and CAR-T cell expansion and persistence. Patients were closely monitored for 6 months post-infusion. Thereafter, disease assessments, physical examinations, and hematologic tests were conducted every 3 months for a total follow-up duration of 2 years.

Inclusion Criteria:

1. Age between 18 and 70 years (inclusive);
2. Estimated life expectancy of more than 12 weeks;
3. Diagnosis of multiple myeloma confirmed by physical examination, pathological evaluation, laboratory tests, and imaging studies;
4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels less than 3 times the upper limit of normal (ULN);
5. Karnofsky Performance Status (KPS) score > 50%.
6. Ineligible for ASCT.

Exclusion Criteria:

1. Pregnant or lactating women, or women planning to become pregnant within the next six months;
2. Transduction efficiency of targeted lymphocytes <10%, or expansion fold <5× under CD3/CD28 co-stimulation, as determined by feasibility screening;
3. History of severe allergies or hypersensitivity, especially to interleukin-2 (IL-2);
4. Significant dysfunction of vital organs including the heart, lungs, or brain;
5. Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study