Treatment of relapsed/refractory multiple myeloma with weekly cyclophosphamide plus bortezomib plus prednisone or dexamethasone (CyBor-P/D): Updated experience at Princess Margaret Cancer Centre (PMCC).
Bibliographic record
Abstract
e19568 Background: We previously defined the efficacy of CyBor-P, a 28-day regimen consisting of cyclophosphamide 300 mg/m2 (days 1,8,15, 22), bortezomib 1.5 mg/m2 (days 1,8, 15) and prednisone 100 mg q 2 days in a phase I/II trial involving patients (pts) with relapsed/refractory multiple myeloma (rel/refr MM) [Reece et al, JCO 2008; 26; 4777]. Variations of this regimen have since been reported (bortezomib weekly and replacement of prednisone with dexamethasone), along with its use as first-line therapy. Methods: We now retrospectively review our PMCC experience with CyBor-P/D in rel/refr pts who received ≥ 1 cycle of this regimen to gauge its effectiveness in the real-world setting. Results: Between 2007 and 2013, 98 pts with rel/refr MM received CyBor-P (prednisone 50-100 mg q 2 days) or CyBor-D (dexamethasone 20-40 mg/wk). Median age was 64 yrs (36-86); median # prior regimens was 2 (1-6), including ASCT (75%), bortezomib (28%) and IMiDs (85%). Median creatinine was 94 umol/L (range 53-900). Pts received a median of 5 cycles (range 1-47). Overall response rate (ORR) was 68%, with 42% achieving ≥ VGPR; 24% had stable disease. Median PFS was 14.9 mos (95% CI 12-17.9) and OS 24.2 mos (95% CI 20.2-28.1). Reasons for discontinuation included: progression (44%), planned 2ndASCT (11%), neuropathy (5%), cytopenias (4%), other (5%). The Table shows outcomes according to prior bortezomib exposure. There were no significant outcome differences between bortezomib-naïve pts, or pts treated at first vs. > first relapse. Cytogenetic data was incomplete but 9/15 (60%) del13q and 3/6 (50%) t(4;14) pts responded. Conclusions: 1) The ORR of 68% and PFS of 14.5 mos seen with CyBor-P/D in the real-world setting compare favorably with other 3-drug regimens; 2) CyBor-P/D is well-tolerated; 3) This regimen is effective as re-treatment in bortezomib-exposed pts. Patient Group N ORR (VGPR) Median PFS, mos Median OS, mos No prior bortezomib 61 68% (43%) 14.5 24.3 CyBor-P/D as induction before 2nd salvage ASCT 9 89% (33%) 20.8 Not reached Re-treatment after prior CyBor-P/D 13 53% (38%) 13.0 12 Re-treatment after other bortezomib regimen 14 72% (50%) 15.9 11.1
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".