Incidence and Characteristics of Secondary Myelodysplastic Syndrome Developing During Lenalidomide-Based Regimens In Relapsed and/or Refractory Multiple Myeloma Patients
Bibliographic record
Abstract
Abstract Abstract 1877 Secondary myelodysplastic syndrome and acute myelogenous leukemia (2° MDS/AML) are well-known complications that can occur after alkylating agent therapy for multiple myeloma (MM) or other cancers. However, until recently, the survival of MM pts was relatively short, a feature which may have contributed to a relatively low reported incidence of this complication in MM. The introduction of novel agents has improved survival rates of MM pts; lenalidomide (len) + dexamethasone–currently approved for MM after one prior therapy– is one of the main regimens that has contributed to this finding. Since alkylating agents—either given orally or as part of high-dose melphalan + ASCT—still remain an important component of myeloma therapy, more pts may survive to be at risk for 2° MDS/AML. Using the MM database at PMH, we retrospectively reviewed the charts of pts with relapsed/refractory (rel/ref) MM treated with len-based regimens to determine the incidence and characteristics of 2° MDS/AML that developed during this therapy. Between 06/2006—11/2009, 230 pts with rel/ref MM received ≥ 1 cycle of len + corticosteroids (195 pts), len alone (3 pts) or cyclophosphamide + len + prednisone (CPR) (32 pts). 2° MDS/AML developed in 6 (2.6%) at a median of 76 months (range 43–190) from the time of diagnosis of MM and 61 (21-168) months from the time of initiation of len regimens. The cytogenetic changes were variable, but 4 pts had deletions of all or part of chromosome 5. The characteristics of pts, at the time of starting len, in those who later developed (+) or did not develop (-) 2° MDS/AML during therapy, are shown in Table 1. The median number of len cycles given was 21 (9-35) versus 9 (1-50) and Grade 3–4 neutropenia occurred during len in 50% versus 54% in those with and without 2° MDS/AML, respectively. G-CSF was used in 50% of pts who developed MDS compared with 54% who did not. The cumulative incidence of 2° MDS/AML (95% CI) was 1% (0-5 %) at 1 yr, 3% (1-9 %) at 8 yrs and 7% (2-19 %) at 12 yrs from the time of diagnosis of MM, while the cumulative incidence was 1% (0-5 %) at 1 yr, 4% (1-9 %) at 2 yr and 9% (4-12%) at 3 yrs after commencing len-based regimens. We conclude: 1) pts developing MDS/AML while on len regimens were slightly older and had less often received prior ASCT, thalidomide and bortezomib; 2) the pattern of MDS development is consistent with the hypothesis that extensive exposure to cytotoxic agents, particularly oral alkylating agents (which had been given to 5/6 [83%] of affected pts), increases the risk of 2° MDS/AML; 3) although len is effective therapy in some pts with MDS, its use does not protect heavily pre-treated MM pts from this complication. Disclosures: Reece: Celgene: Honoraria, Research Funding. Off Label Use: Combination of lenalidomide and cylophosphamide plus prednisone in relapsed and refractory myeloma patients. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria. Trudel:Celgene: 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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| 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".