Lenalidomide, bortezomib, pegylated liposomal doxorubicin hydrochloride, and dexamethasone in newly diagnosed multiple myeloma: Initial results of phase I/II MMRC trial
Bibliographic record
Abstract
8517 Background: Three-drug combinations with lenalidomide (Revlimid, Rev) and bortezomib (Velcade, Vel) are highly active in previously untreated multiple myeloma (MM). Among the most active are RVD (Revlimid, Velcade, Dexamethasone) and VDD (Velcade, Doxil, Dexamethasone) with ≥ PR rate of 100% and 93%, and a CR/nCR rate of 44% and 40%, respectively. Pre-clinical evaluations suggest that adding pegylated liposomal doxorubicin hydrochloride (Doxil, Dox) to RVD (RVDD) may have higher activity. This phase I/II study was designed to determine the maximum tolerated dose (MTD) of RVDD, assess safety and evaluate efficacy of this 4-drug regimen in newly diagnosed MM. Methods: Four dose levels are being evaluated: Rev 15–25 mg (days 1–14), Vel 1.3 mg/m2 (days 1, 4, 8, 11), dexamethasone (Dex) 20/10 mg (cycles 1–4/5–8; days of and after Vel), Dox 20 and 30 mg/m2 (day 4), with dose assignment for patients (pts) according to the TITE-CRM algorithm. Eight 21-day cycles are planned with 38 pts to be treated at the MTD in phase II. Pts who achieve ≥ PR can proceed to autologus stem cell transplant (ASCT) after ≥ 4 cycles, while all others receive 21-day maintenance cycles with Rev (days 1–14), Vel (day 1 and 8), and Dex (days of and after Vel) at the doses tolerated by the end of initial treatment. Results: The study has enrolled 23 pts to date. Four pts received level 1 (Rev/Dox 15/20), 11 pts level 2 (Rev/Dox 20/20, and 8 pts level 3 (Rev/Dox 25/20). Nineteen pts are evaluable for toxicity after completion of a median of 4 cycles (range 1–8). Two pts developed DLT at dose level 2, consisting of grade (G) 3 asymptomatic neutropenia and G3 elevation of transaminase. The MTD has not been reached. Overall, toxicities have been manageable with no additional G3 hematologic events. There have been 4 additional G3 non-hematologic events including one case each of pneumonia, DVT, fatigue, and hypotension. After a median of 12 (range 3–24) weeks of treatment, preliminary response rates by modified EBMT/UC in 19 evaluable pts are: 95% ≥ PR, 47% ≥ VGPR, 26% CR/nCR. Conclusions: RVDD is well tolerated in newly diagnosed MM and appears highly active with an overall response (≥ PR) of 95%. Accrual is ongoing, with updated toxicity and efficacy data to be presented at the meeting. [Table: see text]
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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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 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".