Phase II Testing of Lenalidomide Plus Melphalan for Previously Untreated Older Patients with Multiple Myeloma: The NCIC CTG MY.11 Trial
Bibliographic record
Abstract
Abstract Introduction: The NCIC CTG previously reported the results of a dose-finding trial testing the combination of Melphalan (M) and Lenalidomide (L) in previously untreated patients with multiple myeloma who were ineligible for stem cell transplantation because of older age and/or comorbidity (White, Blood2007; 110: 63a). Using a 28-day schedule, M (dose indicated as mg/m2/day given on days 1–4) and L (dose indicated in mg/day given on days 1–21) was associated with excess toxicity with the regimens M9L10, M4L15 and M6L10. We concluded that phase II testing of M5L10 was warranted and now report the results of this testing. Methods: Previously untreated symptomatic and consenting patients with tissue-confirmed plasmacytosis and a measurable M-protein were eligible provided that they had acceptable hematologic and biochemical laboratory parameters and no precluding comorbidities. Planned treatment consisted of M 5 mg/m2 days 1–4 and L 10 mg days 1–21, given every 28 days for 12 cycles. As our intent was to determine dose levels that could be given independently of G-CSF, primary prophylaxis with G-CSF was not included but use of G-CSF for established neutropenia was permitted. A hematologic dose limiting toxicity (H-DLT) was defined as the need for 2 dose attenuations of L or 1 dose attenuation of M occurring within the first 3 treatment cycles. Responses to treatment were classified using 1998 EBMT criteria and assessed after 2 and 6 cycles of therapy. Results: The intended sample size was 41 patients; 35 patients (1 ineligible) were enrolled before the study was closed due to observing a frequency of DLTs that surpassed predefined boundaries. Of the 34 eligible patients, median age was 73.4 yrs and ISS was stage I = 13, stage II = 11 and stage III = 10. Prior to study closure, 27 patients were evaluable for DLT; 7 (26%) did not experience a DLT. Among the remaining 20 (74%) patients, non-hematologic (N=2) and hematologic (N=18) DLTs requiring dose attenuations were seen within the first 3 treatment cycles; the H-DLTs included severe or prolonged neutropenia (N=11), thrombocytopenia (N=2) or both (N=5). One fatal serious adverse event was observed, this was due to a stroke. The other non-hematologic DLT was a cranial nerve III palsy which subsequently resolved. Responses after 2 cycles were evaluable in 21 patients and included partial response (PR) = 11, minimal response = 6, no change = 2 and progressive disease (PD) = 2. For those patients without PD after 2 cycles, responses after 6 cycles were evaluable in 8 and included PR = 6, stable response = 1 and PD = 1. Conclusion: Although M + L is an active combination for previously untreated myeloma patients, the regimen is associated with considerable myelosuppression. Without the routine use of GCSF, the doses used in the MY.11 study were not tolerable. Inability to use planned doses may have compromised the efficacy of the combination.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 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".