The role of salvage induction chemotherapy after azacitidine (AZA) treatment failure.
Bibliographic record
Abstract
7078 Background: Hypomethylating agents (HMA) such as AZA, are considered standard of care for patients (pts) with IPSS Int-2 or High-risk MDS. These agents are not curative. Many centers have used HMAs as a bridge to alloSCT in pts with MDS in an attempt to reduce tumor burden and prolong time to progression to AML. However, pts are at risk of AZA treatment failure, which may delay or prevent subsequent alloSCT. Recent data have demonstrated poor responses to intensive chemotherapy after AZA failure [ORR of 0% (0 of 4 pts) to 14% (3 of 22 pts) (J Clin Oncol 2011; Br J Haematol 2012)]. Methods: This retrospective analysis evaluates the outcomes of 18 pts with MDS, CMML and AML, who failed AZA therapy, and subsequently received induction chemotherapy at the Princess Margaret between July 2009 and December 2012. Results: Median age was 57.7 y (range, 19 - 75 y); only 1 pt was > 70 y. 56% were male. Of the 18 pts, 83% were treated for MDS, 6% CMML-2, and 11% AML. IPSS was Int-2/High-risk in 16 pts and Int-1 risk in 2 pts. 83% of pts had been treated with AZA as first-line therapy. Two pts had received growth factors & 1 pt hydroxyurea prior to AZA. Median number of AZA cycles administered was 5.5 (range, 1 - 18) with 72% of pts receiving < 6 cycles. Eleven (61%) pts had primary AZA failure, 5 (28%) secondary AZA failure, and 2 (11%) were taken off AZA to receive induction chemotherapy as an HLA-identical donor was found. At the time of induction chemotherapy, 15 pts had s/tAML, 2 RAEB-2 and 1 CMML-2. Cytogenetic risk was intermediate in 4 and poor in 11 pts, respectively. Karyotype analysis was not done or inconclusive in 3 pts. ORR was 44% and 37.5% in all pts and in AZA failures only, respectively. CR rate was 22% and 25%, CRi 27% and 12.5%, and MLFS 6% and 0% in all pts and in AZA failures only, respectively. Four pts died during induction. Four of 8 responders received an alloSCT, with the remaining 4 pts relapsing (3 while awaiting an alloSCT). Median F/U of all pts was 12.6 mos, with a median OS of 8.3 mos. Conclusions: Contrary to prior reports, salvage induction chemotherapy can yield responses in a significant number of pts who have failed AZA therapy. However, response duration and OS remain poor for AZA treatment failures. There is an unmet need for novel therapeutic agents in this group of patients.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".