RITUXIMAB SUPER-RESPONDERS: CHARACTERISTICS OF PATIENTS WITH MORE THAN 3 YEARS RESPONSE TO A SINGLE CYCLE OF TREATMENT
Bibliographic record
Abstract
PV266 / #632 Poster Topic: AS24 - SLE-Treatment Background/Purpose Rituximab has been used to treat SLE for 20 years but efficacy is limited by inadequate B cell depletion. Emerging therapies such as CD19 CAR-T-cells have been reported to induce deeper B cell depletion and thereby drug-free remission up to 18 months. However, with rituximab, we showed that depth of depletion and rate of repopulation were highly variable, and related to patient factors eg, complement levels and FCGR genotype. Using highly sensitive flow cytometry protocol, plasmablast repopulation below 0.0008 x 10^9/L predicted longer response.[1] Anecdotally, we have observed “rituximab super-responders” with sustained remission after 1 cycle of rituximab. The objectives of the study were to assess a) incidence of rituximab-super-response, with or without concomitant immunosuppressant; and b) factors associated with super-response after the first rituximab cycle, with a view to personalize anti-CD20 antibodies in SLE. Methods We conducted an observational study of consecutive rituximab-treated SLE patients in a single center over 20 years who had followed an on-demand retreatment strategy. Usual practice was to continue concomitant immunosuppressants but taper glucocorticoids. Univariable and multivariable logistic regression analyses were performed to identify factors associated with rituximab super-response, with p<0.1 associated with the deviance used for inclusion into the model. Results Of 149 first-cycle-rituximab-treated patients, 114 were included in the study [excluded due to nonresponse in Cycle 1=17; received fixed retreatment at 6-9 months=15; deaths within the first 3 years=2; and discontinued rituximab due to psoriasis=1]. Based on survival curve, we defined super-responders as >3 years (Figure 1). This occurred in 23/114 patients (20%) with median (IQR) duration of response 263 (212,423) weeks. At baseline, rituximab-super-responders had: mean (SD) age 35 (14) years, 20/23 (87%) female, ancestry European=9/23 (39%); South Asian=6/23 (26%), Chinese/SE Asian=2/23 (9%); African=5/23 (22%); and Mixed=1/23 (4%)], concurrent APS 6/23 (26%), disease duration 2.8 (1,5) years, median (IQR) SLEDAI-2K 11 (7,15), and median (IQR) numeric BILAG score 21 (13,25). Sustained suppression of plasmablasts was observed at 3 years: median (IQR) 0.0008 (0.0002,0.0045). 8/23 Rituximab-super-responders (34.8%) were not prescribed immunosuppressants or withdrew them during follow-up (drug-free remission). In multivariable analysis of 114 patients, factors associated with duration of response >3 years were non-European ancestry (OR 4.6, 95% CI 1.6-12.7)) and concurrent APS, (3.2, 0.99-10.35), while longer disease duration (0.89,0.80-0.99 per year) was associated with lower odds of rituximab-super-response. No other factors (age, sex, anti-dsDNA+, low C3/C4, number of antibodies, concomitant immunosuppressant, disease activity score, and active BILAG A/B in 5 most frequent domains) were predictive. Figure 1: Kaplan-Meier plot of relapse-free survival after a first cycle of rituximab Conclusions Sustained drug-free remission is not confined to patients who have received CAR-T CD19 but may be observed following rituximab. 1 in 5 rituximab-treated patients had >3 years response to their first cycle, and 1 in 12 had sustained, immunosuppressant-free remission. Rituximab-super-response is associated with patient characteristics typically denoting disease severity (early disease, non-European ancestry and APS), as well as marked suppression of plasmablast repopulation. This suggests that sustained drug-free remission is a feature of the overall immune environment rather than the modality of B cell killing. Given their safety and low cost, anti-CD20 monoclonal antibodies in early poor prognosis SLE may be preferable to intensive therapy in refractory disease. Future work will include more detailed biomarker evaluation of this cohort. References: [1.] Md Yusof MY. Ann Rheum Dis 2017;76(11):1829-36.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".