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S196: ELRANATAMAB, A B-CELL MATURATION ANTIGEN (BCMA)-CD3 BISPECIFIC ANTIBODY, FOR PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: EXTENDED FOLLOW UP AND BIWEEKLY ADMINISTRATION FROM MAGNETISMM-3

2023· article· en· W4385644723 on OpenAlexaff
Mohamad Mohty, Michael H. Tomasson, Bertrand Arnulf, Nizar J. Bahlis, Paula Rodríguez‐Otero, Joaquín Martínez‐López, Cyrille Touzeau, Hang Quach, Julien Depaus, Hisayuki Yokoyama, Salomon Manier, Noopur Raje, Marc S. Raab, Emma Searle, Eric Leip, Sharon T. Sullivan, Akos Czibere, Andrea Viqueira, Alexander M. Lesokhin

Bibliographic record

VenueHemaSphere · 2023
Typearticle
Languageen
FieldMedicine
TopicMultiple Myeloma Research and Treatments
Canadian institutionsInstitute of Cancer ResearchUniversity of Calgary
Fundersnot available
KeywordsMedicineDiscontinuationInternal medicineRefractory (planetary science)Adverse effectGastroenterologyMultiple myelomaSurgery

Abstract

fetched live from OpenAlex

Background: MagnetisMM-3 (NCT04649359) is an open-label, multicenter, registrational phase 2 study evaluating the efficacy and safety of elranatamab monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Aims: Results from the MagnetisMM-3 trial in patients naïve to BCMA-directed therapies (Cohort A) after >1 y of follow-up, including patients who switched from QW to Q2W elranatamab administration, are presented. Methods: Eligible patients were refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody. Patients received SC elranatamab in 28-d cycles with step-up doses of 12 mg on C1D1 and 32 mg on C1D4 followed by 76 mg QW beginning C1D8. Patients treated for 6 cycles and achieving partial response (PR) or better with response persisting ≥2 mo were switched to 76 mg Q2W, 46 and 58 patients are included in the Q2W efficacy and safety analyses, respectively. Results: Overall, 123 patients received elranatamab. Median patient age was 68.0 y (range, 36−89), 63.4% of patients had an ECOG PS ≥1 and median prior lines of therapy was 5.0 (2−22); 96.7% and 42.3% of patients were triple-class- and penta-drug refractory, respectively. At data cutoff (~12 mo after last patient initial dose), the median follow up was 12.8 mo (0.2−22.7); 34.1% of patients remained on treatment. Most common reasons for permanent treatment discontinuation were progressive disease (39.0%) and adverse events (13.8%). Objective response rate per blinded independent central review (BICR) was 61% (95% CI 51.8−69.6), with 39 (31.7%) patients with complete response (CR) or stringent CR (sCR); very good partial response (VGPR) and PR were achieved in 29 (23.6%) and 7 (5.7%) patients, respectively. MRD-negativity (threshold 10–5) was achieved by 92.0% (n=23/25) of evaluable patients. Median duration of response (mDOR) has not been reached (95% CI 12.9−NE) and DOR at 12 mo was 74.1% (95% CI 60.5−83.6). In patients with CR/sCR or VGPR, mDOR was not reached by 12 mo; in patients with PR, mDOR was 5.2 mo (95% CI 1.6−NE). There were 46 responders by BICR who switched to Q2W dosing ≥24 wk prior to the data cut-off; among these patients, 80.4% maintained/improved their response ≥24 wk after the switch. Median progression-free and overall survival have not been reached by 12 mo, and the respective rates (95% CI) at 12 mo were 57.1% (47.2−65.9) and 62.0% (52.8−70.0). Most common Grade 3/4 treatment emergent adverse events were hematologic; Grade 3/4 non-hematologic events reported in ≥5% of patients were COVID-pneumonia (10.6%), hypokalemia (9.8%), pneumonia (7.3%), sepsis (6.5%), hypertension (6.5%), ALT increased (5.7%), and SARS-COV-2 test positive (5.7%). Among patients who switched to Q2W dosing, the incidence of Grade 3/4 AEs decreased by >10% after the switch. Summary/Conclusion Elranatamab remains efficacious and well tolerated in patients with RRMM after >1 y of follow-up. Updated analysis with a median follow up of ~15 mo, the longest of all phase 2 BCMA-CD3 bispecific antibody studies, including the outcome of patients who switched to the Q2W dosing, will be presented. These results support the continued development of elranatamab both as a monotherapy and in combination with standard or novel therapies for patients with MM. Keywords: Bispecific, Clinical trial, Multiple myeloma, B-cell maturation antigen

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)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.156
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

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

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 head0.019
GPT teacher head0.279
Teacher spread0.260 · 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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Citations7
Published2023
Admission routes1
Has abstractyes

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