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P1078: MOSUNETUZUMAB DEMONSTRATES DURABLE RESPONSES IN PATIENTS WITH RELAPSED AND/OR REFRACTORY FOLLICULAR LYMPHOMA WHO HAVE RECEIVED ≥2 PRIOR THERAPIES: UPDATED ANALYSIS OF A PIVOTAL PHASE II STUDY

2023· article· en· W4385667651 on OpenAlexaff
Laurie H. Sehn, Nancy L. Bartlett, Matthew J. Matasar, Stephen J. Schuster, Sarit Assouline, John Kuruvilla, Mazyar Shadman, Chan Y. Cheah, Keith Fay, Matthew Ku, Loretta J. Nastoupil, Michael C. Wei, Shen Yin, Iris To, Nan Hu, Juliana Min, Elicia Penuel, Anton Belousov, Alexandre Coimbra, Skander Jemaa, Brendan C. Bender, David C. Turner, Lihua E. Budde

Bibliographic record

VenueHemaSphere · 2023
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsPrincess Margaret Cancer CentreJewish General HospitalMcGill UniversitySpinal Cord Injury BCUniversity of British Columbia
Fundersnot available
KeywordsMedicineFollicular lymphomaInternal medicineRefractory (planetary science)Clinical endpointPhases of clinical researchSurrogate endpointLymphomaClinical trialOncologySurgeryGastroenterology

Abstract

fetched live from OpenAlex

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. In a pivotal Phase II study (NCT02500407; GO29781), fixed-duration Mosun demonstrated a high rate of complete responses (CRs) and durable responses in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy. Mosun has a manageable safety profile, supporting its use in an outpatient setting (Bartlett et al. 2022). Aims: We report the efficacy outcomes for pts with R/R FL and ≥2 prior lines of therapy who achieved CR by the end-of-treatment (EOT), with a median follow-up of 28.6 months. Methods: Eligible pts with R/R FL (Grade [Gr] 1–3a) and ≥2 prior therapies were enrolled. All pts provided informed consent prior to study entry. Mosun was administered intravenously in 21-day cycles with step-up dosing in Cycle (C) 1 (C1 Day [D] 1, 1mg; C1D8, 2mg; C1D15/C2D1, 60mg; C3D1 and onwards, 30mg). Hospitalization for treatment was not required. Pts achieving CR by C8 completed treatment with no further cycles; pts with a partial response (PR) or stable disease received up to 9 further cycles (17 in total). The primary endpoint was IRC-determined CR rate (as best response; Cheson 2007 criteria). Exploratory analyses assessed the association between total metabolic tumor volume (TMTV) at baseline (BL), as a surrogate for tumor burden, and clinical efficacy and safety. TMTV was derived from PET images at study entry using an AI-based model (Jemaa et al. 2022). Results: Ninety pts with R/R FL and ≥2 prior therapies were enrolled. Of these, 54 pts (60%) achieved CR as best response: 49 pts (54%) achieved CR at EOT; 1 pt with a CR experienced disease progression (PD) in C8; and 4 pts achieved CR after EOT due to delayed bone marrow confirmation. In the 49 pts with CR at EOT, median age was 63 years (range: 29–90), 82% had stage III/IV disease, and median number of prior lines of therapy was 3 (range: 2–10). As of July 8, 2022, median time on study was 28.6 months. Among the 49 pts who achieved CR at EOT, median duration of CR (DOCR; INV-assessed) was not reached (NR); 24-month DOCR rate after first CR was 65% (95% CI: 39–90). Median progression-free survival (PFS) was NR; 24-month PFS rate was 77% (95% CI: 63–91; Table). Two years after the end of fixed-duration treatment, 67% of these 49 pts remained free of PD or death. Of the 54 pts with CR as best response, 33 pts achieved their first CR by the first mandatory tumor assessment at 3 (±0.5) months (early CR) and 21 pts achieved their first CR after the month 3 assessment (late CR), including 5 pts with a PR that converted to a CR after >8 cycles of treatment. Median duration of response (DOR) was NR in patients with an early or late CR. In pts with PR as best response (n=16), median DOR was 4 months (95% CI: 3–7). Median TMTV at BL (n=82) was 139cm3 (range: 0–4858). No correlation was observed between BL TMTV and best overall response. A higher rate of Gr ≥2 cytokine release syndrome (CRS; ASTCT 2019 criteria) events was observed in pts with bone or bone marrow metabolic disease burden (n=24) versus those without (n=58; 33% vs 14%, respectively). Summary/Conclusion: Fixed-duration Mosun monotherapy demonstrated a high CR rate at EOT in pts with R/R FL, with a high proportion remaining event-free 2 years after EOT. Exploratory analyses did not suggest an association between the timing of the first CR and DOR. TMTV at BL was not associated with response to Mosun; however, Gr ≥2 CRS events were more common in pts with bone or bone marrow metabolic disease burden versus those without.Keywords: Relapsed lymphoma, Non-Hodgkin’s lymphoma, Bispecific, Follicular 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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient 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 score0.064
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.003
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 head0.022
GPT teacher head0.310
Teacher spread0.288 · 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".

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Citations6
Published2023
Admission routes1
Has abstractyes

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