Association of Minimal Residual Disease Negativity Rates With Progression Free Survival in Frontline Therapy Trials for Newly Diagnosed Multiple Myeloma: A Meta-analysis. 2023

Joseph Ficek, and Eleftheria Kalaitzaki, and Shuai Sammy Yuan, and Alessandra Tosolini, and Ling Du, and Brandon E Kremer, and Katherine Davy, and Helen Zhou, and Tai-Tsang Chen
Oncology Statistics, GSK, Collegeville, PA. Electronic address: joseph.a.ficek@gsk.com.

Current frontline therapies for newly diagnosed multiple myeloma patients have significantly prolonged progression-free survival (PFS). This has led to interest in minimal residual disease negativity (MRDng) as an efficacy-response biomarker and possible surrogate endpoint. A meta-analysis was conducted to explore the surrogacy of MRD for PFS and quantify the relationship between MRDng rates and PFS at the trial level. A systematic search was conducted on phase II and III trials reporting MRDng rates along with median PFS (mPFS) or PFS hazard ratios (HR). Weighted linear regressions were conducted relating mPFS to MRDng rates, and relating PFS HRs to either odds ratios (OR) or rate differences (RD) for MRDng in comparative trials. A total of 14 trials were available for the mPFS analysis. log(MRDng rate) was moderately associated with log (mPFS), with a slope of β = 0.37 (95% CI, 0.26 to 0.48) and R2 = 0.62. A total of 13 trials were available for the PFS HR analysis. Treatment effects on MRDng rates were correlated with the corresponding effects on PFS: log (PFS HR) and log (MRDng OR) had a moderate association with β = -0.36 (95% CI, -0.56 to -0.17) and R2 = 0.53 (95% CI, 0.21 to 0.77); log (PFS HR) and the MRDng RD had a stronger association with slope β = -0.03 (95% CI, -0.04 to -0.02) and R2 = 0.67 (95% CI, 0.31 to 0.86). MRDng rates moderately associate with PFS outcomes. MRDng RDs are more strongly associated with HRs than MRDng ORs, with evidence suggestive of potential surrogacy.

UI MeSH Term Description Entries
D009101 Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077982 Progression-Free Survival Length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but the disease does not get worse. Event-Free Survival,Event Free Survival,Progression Free Survival,Survival, Event-Free,Survival, Progression-Free
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D018365 Neoplasm, Residual Remnant of a tumor or cancer after primary, potentially curative therapy. Minimal Residual Disease,Residual Cancer,Residual Tumor,Minimal Disease, Residual,Residual Disease, Minimal,Residual Neoplasm,Residual Tumour,Cancer, Residual,Minimal Residual Diseases,Residual Cancers,Residual Minimal Disease,Residual Minimal Diseases,Residual Neoplasms,Residual Tumors,Residual Tumours,Tumour, Residual
D018572 Disease-Free Survival Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. Survival, Disease-Free,Disease Free Survival,Survival, Disease Free

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