Lenalidomide (Revlimid), Bortezomib (Velcade) and Dexamethasone (RVD) For The Treatment Of Secondary Plasma Cell Leukaemia
Bibliographic record
Abstract
Abstract Introduction Secondary plasma cell leukemia (SPCL) is an aggressive variant of multiple myeloma (MM) characterized by the presence of >20% and/or an absolute number of >2 × 109/L circulating PCs cells in the peripheral blood. Recently, combinations of bortezomib (bor) or lenalidomide (len) with conventional cytotoxic drugs have demonstrated very high rates and quality of response in MM, and, based on this data, we aimed to assess the efficacy of len, bor and dexamethasone (RVD) in SPCL. Methods In this retrospective study, we reviewed the records of all patients (pts) with SPCL treated with RVD at Princess Margaret Cancer Center between 03/09 and 06/12. A total of 9 pts were identified. Pts received oral len 10-15 mg/d on days 1-14 (dose adjusted for creatinine clearance), bor 1.0 or 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles (in 3 pts) and once weekly (in 6 pts) along with dexamethasone (20 mg or 40 mg weekly). Primary endpoints were response rate, progression-free survival (PFS), overall survival (OS), and toxicity. Results Clinical characteristics are showed in Table 1. Pts had received a median of 3 lines of therapy (1-5). Thalidomide, len and bor containing regimens were previously used in 3, 5 and 7 pts respectively. After a median of 3 cycles (1-14), CR was seen in 1, VGPR in 2, PR in 1 and 5 pts progressed while on therapy. Pts who achieved ≥ PR experienced a significantly better PFS (11.67 versus 1.57 months) (p=0.0049). At the time of analysis all of the cases had progressed and died. The median PFS was 5.23 months (range 1.68-31.53) with 2 pts progressing after 27 months. Median OS for the entire group was 5.13 months (range 1.17-32). Furthermore, median OS was significantly longer for pts achieving ≥ PR compared to those who did not (7.93 versus 2.93 months, p=0.0472). The median time to first and best response was 4 and 8 weeks, respectively. Two pts (22.2%) experienced non-hematological grade 3/4 adverse events, including sepsis and pneumonia. Grade 3 and 4 neutropenia and thrombocytopenia occurred in 6 pts, and 3 pts required G-CSF to avoid treatment delays. In conclusion we demonstrated that the combination of RVD is able to obtain responses in 44% of in SPCL cases within one month of therapy. Although the median PFS was only 5.23 months, 2 pts experienced responses exceeding 2 years. Thus, we recommend trying RVD for 1 cycle; if no response is seen, an alternative approach should be utilized. Newer agents such as pomalidomide and carfilzomib should be investigated in this aggressive disease in which the majority of responses are short-lived. Disclosures: Reece: Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Millennium Pharmaceuticals: Research Funding; Novartis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; BMS: Research Funding; Otsuka: Honoraria, Research Funding; Onyx: Consultancy. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Tiedemann:Celgene: Honoraria; Janssen: Honoraria. Kukreti:Millennium Pharmaceuticals: Research Funding; Onyx: Research Funding.
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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 | 0.000 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".