PHASE 1B KEYNOTE‐013 STUDY OF PEMBROLIZUMAB IN PATIENTS WITH CLASSIC HODGKIN LYMPHOMA AFTER BRENTUXIMAB VEDOTIN FAILURE: RESULTS OF >4 YEARS OF FOLLOW‐UP
Bibliographic record
Abstract
Introduction: Programmed death-1 (PD-1) inhibitors are an effective treatment option for patients (pts) with relapsed/refractory classic Hodgkin lymphoma (cHL). The multicohort phase 1b KEYNOTE-013 study (NCT01953692) of the PD-1 inhibitor pembrolizumab (pembro) in pts with hematologic malignancies included cHL as an independent expansion cohort. To better understand the durability of responses in this patient population, we present long-term follow-up results for the cHL cohort. Methods: Pts with cHL who experienced relapse after, were ineligible for or refused autologous stem cell transplantation (ASCT) and whose disease progressed after brentuximab vedotin (BV) therapy were enrolled. Pts received pembro IV 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points were safety and complete remission rate (CRR) per central review. Secondary end points were overall response rate (ORR) duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Data cutoff was September 28, 2018. Results: Among enrolled patients (N = 31), median follow-up was 52.8 mo (range, 7.0-57.6).The median number of lines of prior therapy was 5 (range, 2-15), and in 74% of pts, prior ASCT was ineffective. At analysis, 81% of pts had discontinued, primarily because of progression (48%), and 19% of pts had completed treatment. CRR was 19% and partial remission was 39%; ORR was 58% (18/31) (Table). Median DOR was not reached (Figure). Seven patients had a response duration ≥12 mo; 2 patients had a response duration ≥36 mo. Median PFS was 11.4 mo (95% CI, 4.9-27.8); 24-mo PFS rate was 30% (Figure). Median OS was not reached; 24-mo and 36-mo OS rates were 87% and 81%, respectively. Among pts refractory to (n = 11) and not refractory to (n = 20) first treatment, CRR was 27% and 15% respectively; ORR was 55% and 60%. By transplant status and BV status at baseline, ORR was 69% among pts who received BV after ASCT failure, 57% among pts with failed ASCT and BV before ASCT and 38% among pts who received BV and were ineligible for ASCT (Table). Overall, 22 pts (71%) experienced treatment-related adverse events (TRAEs), with diarrhea (23%) the most common; 6 pts (19%) experienced grade 3-5 TRAEs. Conclusions: After a median follow-up of >4 years, some heavily pretreated pts for whom BV therapy was ineffective maintained long-term response with single-agent pembro. The safety profile of pembro was tolerable and as expected. Keywords: Hodgkin lymphoma (HL); PD-1; Pembrolizumab. Disclosures: Zinzani, P: Consultant Advisory Role: Verastem, MSD, Eusapharma, Sanofi, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, Kyowa Kirin; Other Remuneration: Speaker's Bureau: Verastem, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, MSD, Immune Design, Celgene, Portola, Roche, Eusapharma, Kyowa Kirin. Armand, P: Employment Leadership Position: Merck & Co., Inc., Bristol Myers Squibb Pharmaceuticals, Infinity Pharmaceuticals; Consultant Advisory Role: Merck & Co., Bristol Myers Squibb Pharmaceuticals, Infinity Pharmaceuticals; Research Funding: Merck & Co., Bristol Myers Squibb Pharmaceuticals, Pfizer, Inc, Affimed, Roche, Serventa, Otsuka, Sigma-Tau; Other Remuneration: Travel fees, gifts, and others: Bristol Myers Squibb Pharmaceuticals, Merck & Co.. Ribrag, V: Employment Leadership Position: Gilead, Infinity, Bristol Myers Squibb Pharmaceuticals, Laboratoires Servier, NanoString Technologies, Incyte Corporation; Consultant Advisory Role: Gilead, Infinity, Bristol Myers Squibb Pharmaceuticals, Laboratoires Servier, NanoString Technologies, Incyte Corporation; Research Funding: Amgen; Other Remuneration: Travel fees, gifts, and others: Roche, Bristol Myers Squibb Pharmaceuticals. Kuruvilla, J: Consultant Advisory Role: Merck; Other Remuneration: Payment for lectures including service on speaker's bureau: Merck. Zhu, Y: Employment Leadership Position: Merck. Farooqui, M: Employment Leadership Position: Merck & Co., Inc.; Stock Ownership: Merck & Co., Inc. Nahar, A: Employment Leadership Position: Merck & Co., Inc. Moskowitz, C: Employment Leadership Position: Celgene, Genentech, Merck & Co., Seattle Genetics Inc.; Consultant Advisory Role: Celgene, Genentech, Merck & Co., Seattle Genetics Inc.; Research Funding: Pharmacyclics, Genentech, Merck & Co., Seattle Genetics Inc.
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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 | 0.003 | 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) | 0.002 | 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".