COMPARATIVE EFFECTIVENESS OF SALVAGE CHEMOTHERAPY AND CHIMERIC ANTIGEN T‐CELL RECEPTOR THERAPIES IN R/R DLBCL: A SYSTEMATIC REVIEW AND NETWORK META‐ANALYSIS
Bibliographic record
Abstract
David Hodgson and John Kuruvilla are co-senior investigators Introduction: The optimal salvage chemotherapy (SC) regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) prior to autologous stem cell transplant (ASCT) remains unclear. Head-to-head comparison of chimeric antigen receptor T cell (CAR-T) therapies for second line use in primary refractory DLBCL is lacking. Given these limitations, we conducted a systematic review and network meta-analysis (NMA) of randomized clinical trials (RCTs) to assess the efficacy and safety of SC and CAR-T therapies for R/R DLBCL. Methods: We searched MEDLINE, EMBASE and CENTRAL from Jan 1 2006 to July 7 2022 for RCTs enrolling patients diagnosed with R/R DLBCL following treatment (trt) with at least 1 prior regimen. The primary outcome was overall survival (OS), and secondary outcomes were progression free survival (PFS) and grade ≥ 3 adverse events (AEs). NMA was conducted using a fixed-effect model to synthesize evidence. Surface under the cumulative ranking curve was used to rank the relative effect of compared trt. Results: A total of 22 RCTs (n=4505) met eligibility criteria, 13 included for qualitative synthesis only. NMA of SC (6 RCTs, n=1831) compared 7 trt: GDP (gemcitabine, dexamethasone, cisplatin), rituximab (R)-GDP, ICE (ifosfamide, mesna, carboplatin, etoposide), R-ICE, DHAP (dexamethasone, cytarabine, cisplatin), R-DHAP, ofatumumab (O)-DHAP, ESHAP (etoposide, cytarabine, cisplatin, methylprednisolone). Results indicated that R-GDP had improved OS and PFS over other regimens (Table), and ranked highest for OS and PFS. NMA of AEs showed no differences for infection. NMA of 3 CAR-T RCTs (axi-cel, liso-cel, tisa-cel; n=733) showed that axi-cel and liso-cel had improved PFS over SC and ASCT, while no OS difference was observed. Comparing between CAR-T products, both axi-cel and liso-cel had improved OS and PFS over tisa-cel. Liso-cel ranked highest for PFS. NMA of AEs showed that tisa-cel and axi-cel had higher risk of cytokine release syndrome over SC, while axi-cel had higher risk of neurologic toxicity over SC. Conclusions: Our results suggest that R-GDP may be the optimal regimen for R/R DLBCL prior to ASCT. Both axi-cel and liso-cel had improved PFS over SC and ASCT, while tisa-cel did not. Although liso-cel ranked highest for PFS, longer follow-up is required for comparative survival analysis as data matures. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Therapeutics and Clinical Trials in Lymphoma - Other No conflicts of interests pertinent to the abstract.
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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 | 0.004 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.026 | 0.002 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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 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".