Background: Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM.
Methods: All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life.
Results: Among 45 SMM trials identified, 38 (84.4%) assessed active myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively).
Conclusion: In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/oncolo/oyae219 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Drug Development.
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
University of Kentucky Sanders-Brown Center on Aging, Lexington, KY, USA.
Background: The presence of multiple comorbid pathologic features in late-onset dementia has been well documented across cohort studies that incorporate autopsy evaluation. It is likely that such mixed pathology potentially confounds the results of interventional trials that are designed to target a solitary pathophysiologic mechanism in Alzheimer's disease and related dementias (ADRD).
Method: The UK ADRC autopsy database was screened for participants who had previously engaged in therapeutic interventional trials for Alzheimer's disease, vascular cognitive impairment, dementia, and/or ADRD prevention trials from 2005 to the present.
Drug Development.
Alzheimers Dement
December 2024
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, North Holland, Netherlands.
The lack of an in-vivo pathology marker for synuclein pathology has been a long standing challenge for dementia for Lewy bodies (DLB) research. This issue is critically important for phase II trials, which are often small, requiring the precise measurement of the biological effects, whether disease modifying or symptomatic. Recent advances have enabled the determination of alpha-synuclein pathology status with CSF measurements, using aggregation assays [RT-QUIC].
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of tau aggregates. Research in animal models has generated hypotheses on the underlying mechanisms of the interaction between Aβ and tau pathology. In support of this interaction, results from clinical trials have shown that treatment with anti-Aβ monoclonal antibodies (mAbs) affects tau pathology.
View Article and Find Full Text PDFBackground: Clinical outcome assessments (COAs) are an important part of clinical trials to measure what is meaningful to patients and caregivers. This study aimed to examine trends in Alzheimer's Disease (AD) COAs used in clinical trials, given the FDA's recent emphasis on patient-focused drug development and early AD.
Method: ClinicalTrials.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!