PHASE 1B STUDY OF PEMBROLIZUMAB IN PATIENTS WITH RELAPSED/REFRACTORY PRIMARY MEDIASTINAL LARGE <scp>B</scp>‐CELL LYMPHOMA (<scp>RRPMBCL</scp>): UPDATED RESULTS FROM THE <scp>KEYNOTE</scp>‐013 TRIAL
Bibliographic record
Abstract
Introduction: Current treatments for rrPMBCL often yield poor outcomes, but PMBCL's genetics may make it susceptible to PD-1 blockade. The multicenter, multicohort KEYNOTE-013 (NCT01953692) phase 1b trial evaluates safety, tolerability, and antitumor activity of the anti-PD-1 monoclonal antibody pembrolizumab in patients (pts) with hematologic malignancies. Methods: An independent cohort of KEYNOTE-013 is enrolling PMBCL pts who relapsed after or are ineligible for autologous stem-cell transplant (SCT). Pts initially received pembrolizumab IV 10 mg/kg every 2 weeks (Q2W), later changed to an equivalent regimen of 200 mg every 3 weeks (Q3W). Treatment continues for 2 years or until unacceptable toxicity or confirmed disease progression. Treatment response is radiographically evaluated using 2007 response criteria at week 6, 12, and every 9 weeks thereafter. Primary end points were safety and objective response rate (ORR). Safety population: all pts with ≥1 dose of study drug. Efficacy population: all pts who progress prior to or reach the first efficacy evaluation. Results: By the analysis cutoff date (January 3, 2017), 22 pts had been enrolled in the PMBCL cohort, 21 were treated, and 19 were radiographically evaluable. Overall, 67% of pts had ≥3 prior lines of therapy, and 67% were ineligible for autologous SCT due to chemorefractory disease. Median follow-up duration was 14.3 months (range, 0.6 to 34.7 months). In the safety population, 14 pts (67%) experienced treatment-related adverse events (TRAEs): 4 pts with grade 3 TRAEs (neutropenia n = 2, fatigue n = 1, increased alanine aminotransferase n = 1) and 1 with a grade 4 TRAE (neutropenia). An additional patient had grade 4 venoocclusive liver disease after allogeneic SCT during the follow-up period after pembrolizumab discontinuation. Seven pts had serious AEs. There were no treatment-related deaths. In the efficacy population (19 evaluable pts and 1 with clinical progression before the first efficacy evaluation), ORR was 50%: 5 pts (25%) each achieved partial or complete response (CR). Five others (25%) had stable disease as best response. Of evaluable pts, 15 (79%) had target lesion reductions (Figure). Median duration of response (DOR) was not reached (range, 1.4 to 28.9 months); DOR in pts with CR ranged from 1.4 to 27.1 months. There were 8 ongoing responses, including 5 in pts who discontinued treatment. Seventeen pts discontinued treatment due to progressive disease on imaging (n = 7), clinical progression (n = 5), physician decision (n = 2), patient decision, CR, or AE (n = 1 each); 2 pts were discontinued after completing the maximum 2 years of treatment and remain in remission. Keywords: diffuse large B-cell lymphoma (DLBCL); non-Hodgkin lymphoma (NHL); salvage treatment
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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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".