Pola‐R‐CHP versus R‐CHOEP in young patients with high‐risk diffuse large B‐cell lymphoma
Bibliographic record
Abstract
Introduction: The best treatment for young patients with high-risk diffuse large B-cell lymphoma (DLBCL) is still a matter of debate. Results of the phase 3 R-MegaCHOEP study showed promising results using etoposide in combination with R-CHOP (R-CHOEP). Progression-free (PFS) and overall survival (OS) rates for young patients (18–60 years) with high-risk (age-adjusted IPI 2, 3) DLBCL treated with R-CHOEP were among the best reported for such patients. Recently, the combination of polatuzumab vedotin and R-CHP (pola-R-CHP) was approved for the treatment of DLBCL patients based on the data of the POLARIX study that showed an improvement of PFS following treatment with pola-R-CHP compared to R-CHOP in DLBCL patients with an IPI 2–5. To obtain further insights into the optimal treatment of young (age ≤60 years), high-risk (aaIPI 2, 3) DLBCL patients we retrospectively compared outcomes of such patients treated with pola-R-CHP or R-CHOEP. Methods: Treatment consisted of 6 cycles pola-R-CHP followed by 2 cycles of rituximab (R) given every 3 weeks or 8 cycles of CHOEP given every two weeks plus 6 cycles of R. Event-free survival (EFS), PFS, and OS of DLBCL patients ≤60 years with aaIPI 2, 3 were calculated and major toxicities compared. The Kaplan-Meier method was used to estimate EFS, PFS, and OS in each group. Hazard ratios with 95% CI and log-rank tests comparing pola-R-CHP with R-CHOEP were calculated. P-values <0.05 were considered significant. Results: 113 patients treated with pola-R-CHP and 127 patients treated with R-CHOEP were analyzed. Major patient characteristics differed in aaIPI with more patients in the R-CHOEP group showing an aaIPI of 3 (28% vs. 12%). Two-year EFS-, PFS-, and OS-rates for patients treated with pola-R-CHP were 65.9% (CI: 56.7%, 74.8%), 74.8% (66.5%, 83.0%), and 88.3% (82.3%, 94.3%) as compared to 70.5% (62.5%, 78.5%), 74.9% (67.3%, 82.6%), and 84.6% (78.3%, 91.0%) for patients treated with R-CHOEP with no significant differences for any of these endpoints between treatment regimens. Patients treated with R-CHOEP experienced more hematological toxicity and infections (29.9% ≥ grade 3 infections in R-CHOEP-treated vs. 15.0% in pola-R-CHP treated patients) with 4 treatment-related deaths occurring in patients treated with R-CHOEP and 2 treatment-related deaths following pola-R-CHP, respectively. The research was funded by: This study was sponsored by F. Hoffmann-La Roche Ltd. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract. G. Lenz Consultant or advisory role: F. Hoffmann-La Roche Ltd., Gilead, Janssen, Bristol-Myers Squibb, Novartis, AbbVie, Incyte, Genmab, Constellation, ADC Therapeutics, Karyopharm, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal/Sandoz, Lilly Research funding: Janssen, Bayer, AstraZeneca, MorphoSys Educational grants: AbbVie, Janssen, F. Hoffmann-La Roche Ltd. Other remuneration: F. Hoffmann-La Roche Ltd., Gilead, Novartis, Takeda, Bristol-Myers Squibb, AbbVie, Incyte, ADC Therapeutics, Sobi, Hexal/Sandoz (Speaker's Bureau). F. Hoffmann-La Roche Ltd. (Expert Testimony) H. Tilly Consultant or advisory role: F. Hoffmann-La Roche Ltd., Incyte, Celgene/Bristol-Myers Squibb Honoraria: Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd. Research funding: F. Hoffmann-La Roche Ltd./Genentech, Inc. Educational grants: F. Hoffmann-La Roche Ltd., Janssen M. Ziepert Research funding: F. Hoffmann-La Roche Ltd. B. Altmann Research funding: F. Hoffmann-La Roche Ltd. V. Craine Employment or leadership position: F. Hoffmann-La Roche Ltd. M. Yan Employment or leadership position: Hoffmann-La Roche Ltd. Stock ownership: Hoffmann-La Roche Ltd. C. Herbaux Honoraria: F. Hoffmann-La Roche Ltd., Janssen-Cilag, AbbVie, Gilead Sciences Research funding: Takeda Educational grants: Janssen-Cilag, AbbVie, F. Hoffmann-La Roche Ltd. M. Nickelsen Consultant or advisory role: F. Hoffmann-La Roche Ltd. Honoraria: F. Hoffmann-La Roche Ltd. J. Hirata Employment or leadership position: Genentech, Inc. Stock ownership: F. Hoffmann-La Roche Ltd. D. Sahin Employment or leadership position: F. Hoffmann-La Roche Ltd. Stock ownership: F. Hoffmann-La Roche Ltd. C. Lee Employment or leadership position: F. Hoffmann-La Roche Ltd. Stock ownership: F. Hoffmann-La Roche Ltd. F. Morschhauser Consultant or advisory role: F. Hoffmann-La Roche Ltd./Genentech, Inc., Gilead, Celgene, Bristol-Myers Squibb, AbbVie, Epizyme, Servier, AstraZeneca, Novartis, Genmab Honoraria: F. Hoffmann-La Roche Ltd./Genentech, Inc., Chugai, Eisai Other remuneration: F. Hoffmann-La Roche Ltd./Genentech, Inc. (Expert Testimony) N. Schmitz Consultant or advisory role: Allogene, Miltenyi Stock ownership: Bristol-Myers Squibb Research funding: F. Hoffmann-La Roche Ltd., Janssen Educational grants: Miltenyi, Allogene
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".