Real-World Outcomes with Bortezomib-Containing Regimens and Lenalidomide Plus Dexamethasone for the Treatment of Transplant Ineligible MM Patients: A Multi-Institutional Report from the National Myeloma Canada Research Network (MCRN) Database
Bibliographic record
Abstract
Abstract Introduction: Bortezomib-containing regimens (BCRs) have been the standard frontline approach for the treatment of transplant ineligible multiple myeloma (TIMM) patients in Canada for many years. Based on recent randomized clinical trial results lenalidomide and dexamethasone (Ld) has become another provincially funded option in Canada in the same therapeutic space. We aimed to compare the effect of BCRs and Ld for the treatment of TIMM using the newly-formed Myeloma Canada Research Network Multiple Myeloma Database (MCRN-MM-DB) project. This web-based centralized platform can track and characterize real-world outcomes of patients treated at major Canadian institutions and includes both legacy data dating back to 2007 (from 4 centres) as well as ongoing prospective data collection (from 11 centres) analyzed up to 01/07/18. Patients and Methods: The primary objective was to assess the ORR, PFS and OS for TIMM patients treated with CyBorD/CyBorP, Ld, VMP or VD/VP, each given as reported previously but with dose-adjustments at the discretion of the treating physician to maintain patients on therapy. The two-sided Fisher exact test was used to test for differences between categorical variables. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test; a p value of <0.05 was considered significant. Results: 842 TIMM patients were evaluated. Clinical characteristics are shown in Table 1. Median OS and PFS for the entire cohort were 54.1 and 20.4 months, respectively. ORR and ≥VGPR better rates were 83% and 52% for the entire cohort. A ≥VGPR rate of 53%, 46%, 56% and 51% were observed for patients treated with CyBorD/P, VMP, Ld and VD/VP, respectively (p=0.3). The median PFS was longer for Ld patients (25 months) compared to CyBorD/CyBorP, VMP and Vd/VP (19.3, 20.5 and 13.7 months, respectively), (p=0.03, Fig 1a); there was no significant difference in PFS between the 2 different alkylating-agent containing regimens when combined with bortezomib + steroids (CyBorD/P vs VMP, p =0.9). Median OS was 51, 59.5, 29.4 and 66.5 months for those patients treated with CyBorD/CyBorP, VMP, VD/VP and Ld, respectively (p=0.07, Fig 1b). When the OS and PFS for CyBorD/P (typically given for a fixed duration of 9 cycles) were compared with Ld in a subset analysis, the p-values were 0.08 and 0.008, respectively. Conclusions: 1) OS was not significantly different in patients treated with either a bortezomib-containing triplet that includes an alkylator + steroid or continuous Ld. 2) The BCR triplets and Ld were more efficacious than the bortezomib + steroid doublet (VD/VP) for both OS and PFS although, the small sample size and adverse factors, such as frailty and comorbidities, may have influenced the findings. 3) The results in the real-world setting, i.e., a median PFS in the range of 1.5-2 years and median OS of 4.5-5.5 years, confirm triplet-based BCRs and Ld as current valid standards of care for frontline therapy in TIMM. 5) This study confirms the utility of a large comprehensive national database to benchmark current results for comparison with newer regimens as they are introduced into the Canadian therapeutic landscape. Disclosures Arleigh: Celgene: Honoraria; Janssen: Honoraria. Sebag:Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees. Leblanc:Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Louzada:Janssen: Honoraria; Celgene: Honoraria; amgen: Honoraria; pfizer: Honoraria. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria.
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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 | 0.003 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.006 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 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".