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 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 | 0.002 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".