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This is a prospective, single-center, clinical study to evaluate the efficacy and safety of a fully immunotherapy-based strategy guided by MRD-driven dynamic risk stratification in transplant-ineligible patients with newly diagnosed multiple myeloma.
All subjects will receive standard induction therapy for up to four cycles prior to screening. Following response evaluation, those who meet the inclusion criteria will be enrolled and subsequently stratified into standard-risk and ultra-high-risk groups based on predefined clinical and molecular features.
Patients in the standard-risk group will receive BCMA CAR-T therapy, followed by standard consolidation and maintenance. Patients achieving sustained MRD negativity and stringent complete response (sCR) on two consecutive assessments may enter a treatment-free observation phase. Patients in the ultra-high-risk group will also receive BCMA CAR-T therapy, followed by GPRC5D/CD3 bispecific antibody consolidation and maintenance. Patients achieving sCR and sustained MRD negativity (≥12 months) may enter treatment-free observation. Patients who experience MRD resurgence or loss of response will resume maintenance therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard-risk | Experimental | Enrolled patients will be stratified into standard-risk group based on the absence of ultra-high-risk features, defined as: (1) double-hit cytogenetics, (2) presence of extramedullary disease, or (3) circulating tumor cells (CTCs) ≥2%. Patients in the standard-risk group will receive BCMA CAR-T therapy after standard induction, followed by standard consolidation and maintenance. Patients achieving sustained MRD negativity and stringent complete response (sCR) on two consecutive assessments may enter a treatment-free observation phase. Patients who experience MRD resurgence or loss of response will resume maintenance therapy. |
|
| Ultra high risk | Experimental | Enrolled patients will be stratified into an ultra-high-risk group based on the presence of ultra-high-risk features, defined as: (1) double-hit cytogenetics, (2) presence of extramedullary disease, or (3) circulating tumor cells (CTCs) ≥2%. Patients in the ultra-high-risk group will also receive BCMA CAR-T therapy after induction, followed by GPRC5D/CD3 bispecific antibody consolidation and maintenance. Patients achieving sCR and sustained MRD negativity (≥12 months) may enter treatment-free observation, while those with MRD resurgence or loss of response will resume maintenance therapy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BCMA CAR-T | Biological | Patients will receive single-dose infusion of autologous BCMA-directed CAR-T cellsBCMA CAR-T single dose (3.0 x 10^6 cells /kg). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sustained MRD-negative rate | Rate of patients achieving sustained MRD negativity for more than 12 months | Up to 2 year |
| Progression free survival (PFS) | Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first | Up to 3 year |
| Measure | Description | Time Frame |
|---|---|---|
| Complete response rate (CRR) | CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response accoording to the IMWG criteria. | Up to 2 years |
| MRD negativity rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gang An, PhD&MD | Contact | 86-022-23909171 | angang@ihcams.ac.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences | Recruiting | Tianjin | Tianjin Municipality | China |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D001733 | Bites and Stings |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| GPRC5D/CD3 BiTEs | Drug | Patients will receive GPRC5D/CD3 BiTEs maintenance therapy at a dose of 54 μg/kg every 4 weeks, starting 3 months after BCMA CAR-T infusion. |
|
Rate of patients achieving MRD negativity
| Up to 2 years |
| Overall survival (OS) | Overall survival is defined as the time from the date of diagnosis to the date of death due to any cause | Up to 5 year |
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D011041 | Poisoning |
| D064419 | Chemically-Induced Disorders |
| D014947 | Wounds and Injuries |