Pembrolizumab in combination with lenalidomide and low-dose dexamethasone for relapsed/refractory multiple myeloma (RRMM): Final efficacy and safety analysis.
Bibliographic record
Abstract
8010 Background: Pembrolizumab (pembro) is a monoclonal antibody against PD-1 that helps to restore antitumor immune surveillance. KEYNOTE-023 (NCT02036502) is a phase 1 dose-escalation study evaluating safety and efficacy of pembro in combination with lenalidomide (len) and low-dose dexamethasone (dex) in patients with RRMM. Methods: Patients with RRMM who failed ≥ 2 prior therapies enrolled. Modified 3 + 3 design was used for dose determination with cohorts of 3-6 patients treated with pembro 2 mg/kg Q2W + len 10 mg or 25 mg on days 1-21 and dex 40 mg weekly, repeated every 28 days. After preliminary MTD/MAD identification, additional patients received pembro 200 mg Q2W + len and dex for dose confirmation. Upon final MTD, patients enrolled in the dose expansion phase. Treatment continued for 24 mo or until confirmed disease progression or unacceptable toxicity. Response evaluated monthly using IMWG 2006. Results: 3 DLTs from the pembro 2 mg/kg, 25-mg len cohort were observed in 17 patients in the dose determination/confirmation phase: grade 3/grade 4 neutropenia, grade 3 pneumonia, and grade 3 tumor lysis syndrome with grade 4 hyperuricemia. Based on dose confirmation phase, pembro 200 mg + len 25 mg and dex 40 mg was the MTD/MAD. As of Sep 22, 2015, an additional 33 patients were enrolled in the expansion phase. Median age for the total population was 62 y, 72% had ≥ 3 prior therapies, 76% were refractory to len, and 30% had double refractory disease. 36 patients (72%) experienced treatment-related AEs, most commonly thrombocytopenia (28%) and neutropenia (24%). With a median follow-up of 9.7 mo (range, 4.3-18.4), 13/17 (76%) patients evaluated for efficacy in dose determination/confirmation responded to treatment, including 4 VGPRs (2 in len-refractory) and 9 PRs (3 in len-refractory), with median duration of response 9.7 mo (range, 0+-16.7+). 3 patients (18%) had stable disease. 94% had a reduction in M protein or free light chains. Updated efficacy data for all 50 patients will be presented. Conclusions: Pembro in combination with len and dex was associated with a tolerable safety profile and promising antimyeloma activity in heavily pretreated patients with RRMM. Clinical trial information: NCT02036502.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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) | 0.000 | 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 teacher head, 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".