Pembrolizumab (Pembro) plus lenalidomide (Len) and low-dose dexamethasone (Dex) for relapsed/refractory multiple myeloma (RRMM): Efficacy and biomarker analyses.
Bibliographic record
Abstract
8015 Background: The PD-1 inhibitor pembro blocks interaction of PD-1 with its ligands PD-L1/PD-L2, activating antitumor immunity. Combination of pembro, len, and dex may provide synergistic antitumor activity in RRMM. Methods: Theopen-label, phase 1 KEYNOTE-023 (NCT02036502) study of pembro + len + low-dose dex enrolled patients (pts) with RRMM treated with ≥2 prior therapies (tx). Pts received pembro 200 mg IV Q2W, len 25 mg PO on d1-21, and dex 40 mg PO weekly on each 28-d cycle. Primary end point was safety. ORR was assessed by IMWG 2006. Exploratory biomarker analyses included flow cytometry (FC) (PD-L1, PD-L2 on CD38+CD138+ cells) at screening or predose cycle 1, d 1 bone marrow (BM) aspirate. Absolute and/or relative numbers of circulating immune cells (by FC) and gene expression profile (GEP) (by Nanostring) were evaluated in predose cycle 1, d1 and cycle 2, d1 blood. Results: Median age was 61 y; median (range) prior lines of tx was 4 (1-10); 38 (75%) pts were len-refractory and 27 (53%) pts were double refractory. Most common grade ≥3 tx-related AEs (TRAEs) were neutropenia (33%), thrombocytopenia (18%), and anemia (12%). 2 (4%) pts died (hepatic failure, ischemic stroke) because of TRAEs. Immune-related AEs occurred in 5 (10%) pts. No pneumonitis was reported. For response-evaluable pts, ORR was 50% (20/40; 1 sCR, 14 PR, 5 VGPR); 1 had PD. ORR was 38% (11/29) for len-refractory pts. In 16/32 pts with FC-evaluable BM aspirate with >100 CD38+CD138+ cells, all were PD-L1+, while PD-L2 expression was variable. At cycle 2, d1, frequency of circulating HLA-DR+, central (CD45RO+CCR7-), and effector memory (CD45O+CCR7+) CD8+ T cells significantly increased and naive (CD45RA+) CD8+ T cells significantly decreased; all with multiplicity adjusted P values ≤ 0.01. Conclusions: Pembro + len + low-dose dex has an acceptable safety profile and antitumor activity in pts with RRMM, including len-refractory pts. PD-L1 was expressed in all pts evaluated by FC, whereas PD-L2 expression was variable. Among the pool of circulating T cells in peripheral blood, HLA-DR+ and memory T-cell subset fractions increased after treatment. Clinical trial information: NCT02036502.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".