Minimal Residual Disease, Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, MRD-tailored therapy, MRD status, MRD-negative rates, Survival
Brief summary
The aim of this study was to observe the rate of MRD conversion and the impact on survival in newly diagnosed multiple myeloma (NDMM) patients with persistent MRD positivity after induction and consolidation therapy (autologous hematopoietic stem cell transplantation or consolidation of the original regimen) who were switched to high-intensity therapy, and to compare the rate of persistent MRD-negativity, progression-free survival (PFS), and overall survival (OS) between the two groups in comparison with NDMM patients who achieved MRD-negativity after the same induction and consolidation therapy.
Detailed description
There is still an unmet clinical need as to whether NDMM patients with persistent MRD positive would benefit from switching to high-intensity therapy. The induction regimen (Dara+/- (Vd, Rd, Pd, VRd, VPd)) was selected based on the frail or high-risk status of NDMM patients. Transplantation or consolidation and maintenance regimens were adjusted by MRD status detected by NGF.
Interventions
None listed
Sponsors
FengYan Jin
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must be at least 18 years of age. 2. Subject must have documented newly diagnosed symptomatic multiple myeloma as defined by 2014 International Myeloma Working Group criteria. 3. Subject must have achieved a response (partial response \[PR\] or better based on investigator's determination of response by the IMWG criteria) to at one prior regimen. 4. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. Contraception must begin 4 weeks prior to dosing and continue until at least 3 months after receiving the last dose of the study drug. A woman of childbearing potential must have a negative serum or urine pregnancy tests at screening within 14 days prior to randomization. 5. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
Exclusion criteria
1. Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein \<3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment or end-organ damage. 2. Relapsed and refractory myeloma：Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course. 3. Primary refractory myeloma：Primary refractory myeloma is defined as disease that is nonresponsive in patients who have never achieved a minimal response or better with any therapy. 4. Subject is known or suspected of not being able to comply with the study protocol。 Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted treatment-adjusted MRD-negative rates | through study completion, up to 2 years | To explore the rate of conversion to MRD-negative after adjusting treatment in NDMM patients with persistent MRD-positive status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | through study completion, up to 2 years | PFS were calculated from the enrollment to the first instance of disease progression, relapse, or death |
| Overall Survival (OS) | through study completion, up to 2 years | OS were calculated from the time of enrollment to death or the last follow-up |
| Persistent MRD-negative rates and survival | through study completion, up to 2 years | Persistent MRD-negative rates and survival (including PFS and OS) in both groups compared to NDMM patients who achieved MRD-negativity after the same induction and consolidation therapy |
| Treatment related adverse event(TRAE) | through study completion, up to 2 years | Toxicity and safety will be reported based on the adverse events, as graded by CTCAE V5 and determined by routine clinical assessments. |
Other
| Measure | Time frame | Description |
|---|---|---|
| explore the molecular basis for the dynamic changes and differences in MRD | through study completion, up to 2 years | Bone puncture samples from routine clinical consultations were collected, and single-cell transcriptome sequencing technology was applied to analyze and compare the differences in MM cells (clones) and bone marrow microenvironment (including immunity, inflammation, and stroma) of MRD-transformed and non-transformed patients after adjusting the treatment regimen, using the samples before adjusting the treatment regimen as the baseline control, in order to explore the molecular basis for the dynamic changes and differences in MRD |
| explore the elderly (especially debilitated) patients' MRD-adjusted treatment | through study completion, up to 2 years | For patients ≥65 years old, through the adjusted treatment-adjusted MRD-negative rates to explore the impact of strategy adjustment on elderly patients |
Countries
China
Outcome results
None listed