PB2090: SYSTEMATIC LITERATURE REVIEW OF PROGNOSTIC FACTORS FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA
Bibliographic record
Abstract
Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Multiple myeloma (MM) is a highly heterogenous and incurable malignancy, with nearly all patients eventually relapsing and/or becoming refractory to treatment. Patients with relapsed and/or refractory MM (RRMM) have a poor prognosis; those who are exposed and/or refractory to multiple therapies experience even poorer outcomes. Several studies have identified factors prognostic of outcomes in patients with RRMM; however, an up-to-date synthesis of available evidence is lacking. It is important to have a systematic and evidence-based process to identify relevant prognostic factors to support MM research in a rapidly changing treatment landscape. Aims: The objective of this study was to conduct a systematic literature review (SLR) of prognostic factors associated with objective response rate (ORR), overall survival (OS), progression free survival (PFS), complete response (CR), partial response (PR), or duration of response (DOR) in patients with RRMM. Methods: Database searches were conducted in Ovid MEDLINE and Embase for clinical trials and observational studies published between January 1, 2016 and April 14, 2022. Studies were eligible if they included RRMM patients and an assessment of prognostic significance of any factor on an outcome of interest via multivariate analysis. Eligibility was assessed by two independent reviewers, with discrepancies resolved by consensus or a third independent reviewer. Data from included records were collected using standardized data extraction templates. Factors that were statistically significantly associated with an outcome of interest (p < 0.05, or confidence interval excluding the null value) were extracted. Study quality was assessed using the Quality in Prognosis Studies (QUIPS) tool. Data were summarized descriptively. Results: Of 5,349 records identified through the database and hand searches, a total of 130 records reporting on 125 unique studies were included. Twenty-three (18%) studies were clinical trials, and 102 (82%) were observational cohort studies. The most common limitations in study quality were related to sample representativeness and control of confounders. Ninety-seven factors were statistically significantly associated with at least one outcome in at least one study. The most commonly investigated factors across the 125 included studies were disease stage (n = 27 studies), age (n = 20 studies), prior lines of therapy (n = 20 studies), best response to index therapy (n = 20 studies), cytogenetic risk (n = 19 studies), lactate dehydrogenase (LDH; n = 12 studies), extramedullary disease/plasmacytoma (EMP) (n = 12 studies), and performance status (PS) (n = 10 studies). Worse survival was associated with higher disease stage, older age, more prior lines of therapy, poorer response, high-risk cytogenetics, elevated LDH levels, EMP presence, and worse PS, while worse response was associated with higher disease stage, younger age, more prior lines of therapy, high-risk cytogenetics, and worse PS. Associations between factors and outcomes were largely consistent across studies, although conflicting associations were noted in <10% of studies, and in some studies, poor reporting limited the ability to ascertain the direction of associations. Summary/Conclusion: To our best knowledge, this is the first SLR to investigate prognostic factors for an RRMM population. Using a broad approach to identify relevant studies and adhering to best practices for conducting and reporting of SLRs, this work provides a comprehensive evidence base for factors prognostic of response and survival outcomes in patients with RRMM. Keywords: Prognosis, Systematic review, relapsed/refractory, Multiple myeloma
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".