Outcomes of Previously Untreated Older Patients with Multiple Myeloma (MM) over Time: An Analysis of 3 Consecutive Trials Conducted by the NCIC CTG, 1983–2003.
Bibliographic record
Abstract
Abstract Background: Improved overall survival (OS) over time has been observed in large population databases assessing patients (pts) with MM. Recent interventions, such as routine use of bisphosphonates, and stem cell transplantation for younger pts may account for some of this improvement. It is unclear whether these improvements have been seen in older symptomatic pts. The purpose of this study is to assess outcomes over time of pts > 65 yrs with MM who were entered on 3 consecutive randomized trials conducted by NCIC CTG. Methods: Databases evaluated included MY4 (1983–84; N=173), which compared etidronate to placebo; MY6 (1987–92; N=402), which tested the role of maintenance interferon; and MY7 (1995–2003; N=584), which tested dexamethasone as induction and maintenance therapy. All pts had symptomatic Salmon-Durie stage I or stage II–III MM, were previously untreated, and received melphalan 9 mg/M2 and prednisone 100 mg daily x 4, Q4 weeks; 231 pts in MY7 received melphalan and dexamethasone according to random allocation. We performed uni- and multivariate analyses to compare outcomes of pts ≤ 65 and > 65 yrs of age, to assess outcomes of pts > 65 yrs over time, and to assess other prognostic determinants in pts > 65 yrs. Outcomes of interest included OS, progression-free survival (PFS), myeloma-related survival (MRS), defined as time from registration or randomization until death from myeloma or treatment toxicity, and time from first progression to death (FPTD). Results: All eligible pts were included. By multivariate analyses, patients > 65 yrs had inferior OS (p=0.0003), FPTD (p=0.0006), and a trend for inferior MRS (p=0.08) in comparison with pts ≤ 65 yrs; no difference in PFS was detected. In comparing pts >65 yrs on MY4, MY6 and MY7, important differences in the baseline characteristics of the patients of the 3 trials were noted; pts treated on MY6 received lower median cumulative doses of melphalan (356 mg/M2) than those entered on to MY4 (432 mg/M2) or MY-7 (464 mg/M2). Median unadjusted outcomes of these pts by trial are listed in the table below. By multivariate analysis, pts > 65 yrs entered on to MY4 had a superior MRS in comparison with MY7 (p=0.037) and a trend to superior OS (p=0.053) and FPTD (p=0.06). No differences in PFS between trials were detected. Baseline characteristics associated with inferior OS in pts > 65 yrs included ECOG PS > 1 (p=0.0002), male gender (p=0.001), baseline Hb ≤ 85 g/L (p=0.001), and elevated baseline serum calcium (p=0.01). Conclusions: Patients > 65 yrs have inferior outcomes in comparison with younger pts. We were unable to detect improvements in outcomes of these pts over time. Median unadjusted outcomes of pts age > 65 yrs by trial MY4 (95% CI) MY6 (95% CI) MY7 (95% CI) OS (yrs) 2.38 (1.73–3.32) 2.75 (2.36–3.24) 2.53 (2.32–2.75) PFS (yrs) 1.00 (0.90–1.41) 1.53 (1.38–1.75) 1.80 (1.61–1.92) MRS (yrs) 2.98 (1.78–3.59) 3.30 (2.66–3.79) 2.90 (2.61–3.22) FPTD (yrs) 1.21 (0.76–1.91) 1.27 (0.84–2.02) 0.85 (0.68–1.07)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".