P1129: GLOFITAMAB MONOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) LARGE B-CELL LYMPHOMA (LBCL): EXTENDED FOLLOW-UP AND LANDMARK ANALYSES FROM A PIVOTAL PHASE II STUDY
Bibliographic record
Abstract
Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Glofitamab is a CD20xCD3 bispecific antibody delivered in a fixed course of 12 three-weekly cycles. In a Phase II study (NCT03075696), glofitamab induced high complete response (CR) rates and had manageable toxicity in patients (pts) with R/R LBCL (Dickinson et al. NEJM 2022). Aims: To present an extended follow-up and a landmark analysis to assess the outcomes of pts in CR. Methods: Pts with LBCL and ≥2 prior therapies received 1000mg obinutuzumab pretreatment 7 days prior to the first glofitamab dose. Intravenous glofitamab was given as step-up doses: 2.5mg on Day (D) 1 of Cycle (C) 1, 10mg on C1D8 and 30mg (target dose) on D1 of C2–12 (21-day cycles). The primary endpoint was independent review committee (IRC)-assessed CR rate. Progression-free survival (PFS) and overall survival (OS) post-hoc analyses were performed in responders (landmark for CR at C3 or end of treatment [EOT]). Results: As of Oct 10, 2022, 154 pts had received ≥1 dose of study treatment; baseline characteristics were as previously presented. Median number of prior therapies was 3 (range: 2–7); 33% had received prior CAR T-cells and 85% were refractory to their most recent regimen. Median time on study was 20.1 months (range: 0–32). The investigator (INV)-assessed CR rate (best overall response [BOR]) was 38% (40% by IRC) and overall response rate was 59% (52% by IRC). CR rates were consistent in pts with and without prior CAR-Ts (37% vs 39%). After a median follow-up of 18.3 months (range: 0–30) in pts with a CR (BOR), most CRs (39/59; 66%) were ongoing. Median duration of CR (DoCR) was 24.1 months (95% CI: 19.8–NE); an estimated 70% of pts with a CR at any time remained in remission at 18 months (Figure). The 18-month OS rate was 41% (95% CI: 32.1–49.3). Landmark analyses at 1 year in pts with a CR pre-C3 (PFS rate: 71%, OS rate: 92%) and in pts with a CR at EOT (PFS rate: 80%, OS rate: 94%) showed that most pts were progression free and alive. In a cohort of 101 pts treated with glofitamab doses below the recommended Phase II dose but ≥10mg with longer median CR follow-up (31 months, range: 1–49), the median DoCR was 30.1 months (95% CI: 5.5–NE) and 55% of pts were still in remission at data cut-off. This further confirms the highly durable responses achieved with glofitamab. Cytokine release syndrome (by ASTCT) remained the most common adverse event (AE), occurring in 64% of pts, and was mostly Grade (Gr) 1 (48%) or Gr 2 (12%); Gr 3 (3%) and Gr 4 (1%) events were uncommon. The incidence of AEs and serious AEs was stable compared with earlier analyses, with one new Gr 3 AE (acute kidney injury), one new Gr 2 neurologic AE (agitation) and no new glofitamab-related Gr 5 AEs reported. Summary/Conclusion: Glofitamab continued to demonstrate durable responses, with most pts in CR at EOT still in remission without new AEs. These data support the potential for favorable long-term outcomes with fixed-duration glofitamab for R/R LBCL. Updated analyses, including a larger population with a median CR follow up of approximately 20 months post-EOT, will be presented. Figure: Duration of complete response in patients with R/R LBCL who received glofitamab monotherapyLBCL, large B-cell lymphoma; R/R, relapsed/refractory Keywords: Refractory, Bispecific, Relapsed lymphoma, Non-Hodgkin’s lymphoma
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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 | 0.001 |
| 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 | 0.000 | 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".