407 Relationships between lymphocyte counts and clinical outcomes in patients with recurrent glioblastoma treated with pembrolizumab
Bibliographic record
Abstract
Background Recurrent glioblastoma (rGBM) remains uniformly lethal, with median survival measured in months despite multimodal therapy. Although pembrolizumab produces durable responses in other solid malignancies, activity in rGBM has been disappointing. Emerging data from melanoma, lung, and renal cancers suggest that treatment-induced or disease-related lymphopenia correlates with inferior outcomes on checkpoint inhibition. Because rGBM patients frequently receive lymphocyte-suppressive corticosteroids and chemoradiation, we asked whether a low pre-treatment absolute lymphocyte count (ALC) identifies a subgroup unlikely to benefit from pembrolizumab.Methods We performed a single-center retrospective study of adults with rGBM who received ≥1 dose of pembrolizumab between 1 May 2018 and 31 January 2025 and had lymphocyte counts available at our center. Demographics, MGMT status, prior bevacizumab exposure, dexamethasone use at initiation, and baseline ALC were abstracted from electronic records. Overall survival (OS) was defined as the time from the date of pembrolizumab initiation to the date of death from any cause or last follow up. Median OS (mOS) was calculated with Kaplan-Meier methods, and survival curves were compared with the log-rank test; an exploratory subgroup analysis stratified patients by bevacizumab exposure status. Low ALC was defined as <750 cells/mm 3 in this analysis.Results Forty-three patients met eligibility criteria (median age 59 years, 51% male) and 26% (n = 11) with MGMT methylation. Sixteen patients were bevacizumab-naïve and twenty-seven were bevacizumab-refractory. Across the entire cohort, baseline ALC<750 cells/mm 3 was associated with significantly shorter OS compared to baseline ALC≥750 cell/mm3 (3.4 vs 8.5 months, p=0.0048) with a slightly higher proportion of patients on dexamethasone in low ALC group (75% vs 52%). Among bevacizumab-naïve patients (n=16), mOS was 9.7 months; within this subgroup, patients with ALC<750 cells/mm3 demonstrated a trend toward shorter OS (4 vs. 11 months, p = 0.056) and had slightly higher dexamethasone exposure (80% vs. 55%). In the bevacizumab-refractory group, mOS was 4.3 months; again, low ALC trended toward a shorter OS (2.6 vs 7 months; p=0.075) with similar rates of dexamethasone use (73% vs 50%).Conclusions Baseline lymphopenia preceding pembrolizumab treatment is associated with shorter mOS in patients with rGBM. While the sample size was limited, the consistency of trends across subgroups highlights the need for further validation in larger patient cohorts.
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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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 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".