Significance of Prior HSCT on the Outcome of Salvage Therapy with CPX-351 or Conventional Chemotherapy Among First Relapse AML Patients
Bibliographic record
Abstract
Abstract Abstract 2619 Background: CPX-351 is a liposomal formulation containing a 5:1 molar ratio of cytarabine (Ara-C) and daunorubicin (DNR) designed to maximize anti-tumor synergy (Mayer L, et al. Mol Can Ther, 2006;5:1854). In the Phase 1 study 18/45 AML patients were in 1st relapse with 8 patients ≤65 years of age. All 8 achieved aplasia and 4/8 achieved CR after CPX-351 treatment. (Feldman E, et al. Blood 2008;112:Abst 2984). These observations provided the rationale for a randomized Phase 2b study in 1st relapse AML patients comparing CPX-351 against investigator's choice of salvage regimen. An initial safety and efficacy summary has been submitted to this meeting. This report summarizes the impact of prior HSCT on patient response and 60 day mortality. Methods: Patients ≤65yo with AML in 1st relapse after an initial CR lasting >1 month with ECOG PS= 0–2, SCr <2.0 mg/dL, total bilirubin <2.0 mg/dL, ALT/AST <3 × ULN, and LVEF ≥50% were eligible. Patients were randomized 2:1 to receive CPX-351 (100 u/m2; D 1, 3, 5) or investigators choice of intensive salvage treatment. Up to 2 induction and 2 consolidation courses were allowed. Post remission treatment with HSCT was permitted. Patients were stratified using the European Prognostic Index (EPI) (Breems DA, et al. J Clin Oncol, 2005 Mar 20;23:1969–1978). The primary efficacy endpoint is % survival at 1 year. Results: By November 12, 2010, 126 patients were accrued at 35/46 sites in the US, Canada, France, Poland. Data for response, acute safety, and 60 day deaths are available. Patients in both arms were well balanced by Relapse Free Interval (RFI), age at 1st relapse and cytogenetics. More patients with prior HSCT were assigned to the CPX-351 arm (27% v. 18%). Table 1 shows patient characteristics organized by presence or absence of prior HSCT. Among patients with prior HSCT, the CPX-351 arm had more patients with RFI ≤6 months (36% v. 0%) and younger patients (age <45, 36% v. 13%). The group with no prior HSCT was balanced for overall risk by EPI, RFI, age at 1st relapse, and adverse cytogenetics. For the overall study, the CPX-351 arm had higher aplasia (90% v. 60%) and CR + CRi rate (51% v. 42%) and similar 60 day mortality (15% v. 16%) compared to control. Table 2 shows patient response and early mortality organized by presence or absence of prior HSCT. In the 96 patients (76%) with no prior HSCT, CPX-351 produced an increased rate of aplasia compared to control (90% v. 57%), a response rate that was greater than control (56% v. 41%), and a lower 60 day mortality rate (10% v. 16%). HSCT had little observed impact on outcomes in the control arm but appears to be associated with reduced aplasia (90% to 55%) and response (56% to 36%) and a disproportionate contribution to early deaths (6/12) in the CPX-351 arm. The higher proportion of patients with RFI ≤6 months on the CPX-351 arm (36% v. 0%) may be a contributing factor. Conclusion: Eighty six/126 (68%) patients had unfavorable risk by EPI with equal proportions randomized to each arm of the study. Prior HSCT had little impact on outcomes in the control arm but seemed to have a much larger adverse impact on the CPX-351 arm. This observation of a change in outcome associated with prior HSCT may be due to the higher proportion of patients with RFI ≤6 months on the CPX-351 arm (36% v. 0) and is being evaluated further. Additional data (EFS, % survival at 1 year) are expected later this year. Disclosures: Cortes: Celator: Membership on an entity's Board of Directors or advisory committees. Louie:Celator: Employment.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".