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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

2023· article· en· W4385856058 on OpenAlexaff
Martin Hutchings, Carmelo Carlo‐Stella, Franck Morschhauser, Michael Dickinson, Emmanuel Bachy, Guillaume Cartron, Cyrus Khan, Monica Tani, Joaquín Martínez‐López, Nancy L. Bartlett, Antonio Salar, Joshua Brody, Sirpa Leppä, Pauline Baumlin, Linda Lundberg, James Relf, Yuying Xie, Alessia Bottos, Kathryn Humphrey, Lorenzo Falchi

Bibliographic record

VenueHemaSphere · 2023
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsRoche (Canada)
Fundersnot available
KeywordsMedicineRefractory (planetary science)RegimenPost-hoc analysisInternal medicinePhases of clinical researchClinical endpointToxicityOncologyNuclear medicineClinical trialSurgery

Abstract

fetched live from OpenAlex

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

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.322
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.028
GPT teacher head0.333
Teacher spread0.305 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations2
Published2023
Admission routes1
Has abstractyes

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