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P870: EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN (BCMA)-DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES

2023· article· en· W4385666962 on OpenAlexaff
Salomon Manier, Alexander M. Lesokhin, Mohamad Mohty, Rubén Niesvizky, Christopher Maisel, Bertrand Arnulf, Sarah Larson, Asya Varshavsky‐Yanovsky, Xavier Leleu, Lionel Karlin, David H. Vesole, Nizar J. Bahlis, Carlos Fernández de Larrea, Noopur Raje, Eric Leip, Sharon T. Sullivan, Mohamed Elmeliegy, Andrea Viqueira, Ajay K. Nooka

Bibliographic record

VenueHemaSphere · 2023
Typearticle
Languageen
FieldMedicine
TopicMultiple Myeloma Research and Treatments
Canadian institutionsInstitute of Cancer ResearchUniversity of Calgary
Fundersnot available
KeywordsMedicineInternal medicineMultiple myelomaCytokine release syndromeAdverse effectGastroenterologyBortezomibOncologyRefractory (planetary science)SurgeryCancerImmunotherapyChimeric antigen receptor

Abstract

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Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Studies in the elranatamab MagnetisMM program (MM-1, NCT03269136; MM-3, NCT04649359; MM-9, NCT05014412) enrolled patients with relapsed/refractory multiple myeloma (RRMM) treated with prior BCMA-directed therapies. Aims: The efficacy and safety of elranatamab monotherapy in patients with RRMM and prior exposure to BCMA-directed therapy was evaluated in a pooled analysis. Methods: Eligible patients received at least 1 proteasome inhibitor, 1 immunomodulatory drug, 1 anti-CD38 antibody, and 1 BCMA-directed therapy (antibody drug conjugate [ADC] and/or CAR-T cells). Pooled analysis included patients in MM-1 (n=13) who received SC elranatamab 215−1000 µg/kg; MM-3 (n=64) and MM-9 (n=9) who received the RP2D, SC 76 mg QW. Efficacy endpoints were assessed by investigator per IMWG criteria. Treatment emergent adverse events (TEAEs) were graded by CTCAE (MM-1, v4.03; MM-3 & MM-9, v5.0); cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by ASTCT criteria. Results include data up through ~10 mo after last patient initial dose in all pooled studies. Results: In total, 86 patients were included. Median age was 66.0 y (range, 40−84); 47.7% male. At baseline, 69.8% had an ECOG PS ≥1; 24.4% had high risk cytogenetics; 54.7% had extramedullary disease. Patients received a median of 7.0 (3−19) prior lines of therapy, including BCMA-directed ADC (67.4%) and/or CAR T-cells (41.9%), 9.3% received both. 96.5% and 54.7% of patients were triple-class and penta-drug refractory, respectively; among patients who received ADC and CAR-T cells respectively, 79.3% and 27.8% were refractory to ADC and CAR-T cells. After a median follow-up of 10.3 mo (0.3−32.3), median duration of treatment was 3.3 mo (0.03−30.4). At data cut-off, 24.4% of patients remained on treatment; most common reason for permanent treatment discontinuation was progressive disease (44.2%). Objective response rate (ORR) was 45.3% (95% CI 34.6−56.5), with complete response or better achieved in 17.4% of patients. ORR for patients with prior BCMA-directed ADC and CAR-T cells was 41.4% (95% CI 28.6−55.1) and 52.8% (95% CI 35.5−69.6), respectively. Among responders, median time to objective response was 1.9 mo (0.3−9.3). Median duration of response (DOR) was not reached by 10 mo; the DOR rate at 9 mo was 72.4% (95% CI 54.7−84.2). DOR rate (95% CI) for patients with prior BCMA-directed ADC and CAR-T cells were 67.3% (43.1−83.0) and 78.9% (53.2−91.5) at 9 mo, respectively. Median progression-free survival was 4.8 mo (95% CI 1.9−7.7), and median overall survival was not reached by 10 mo, with a rate of 60.1% (95% CI 48.9−69.6) at 9 mo. Most common (≥25% of patients) TEAEs were CRS (65.1% [G3 1.2%]), anemia (59.3% [G3/4, 46.5%]), neutropenia (44.2% [G3/4, 40.7%]), thrombocytopenia (40.7% [G3/4, 29.1%]), diarrhea (33.7% [G3/4, 0%], and lymphopenia (32.6% [G3/4, 30.2%]). ICANS was reported in 5.8% (G3, 2.3%) of patients. Summary/Conclusion In patients with RRMM and prior exposure to BCMA-directed therapies, elranatamab was efficacious and well tolerated; no new safety signals were observed vs the BCMA-naïve population. Results support treatment with elranatamab in patients with RRMM post BCMA-directed therapy. Keywords: Clinical trial, B-cell maturation antigen, Bispecific, Multiple myeloma

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.036
Threshold uncertainty score0.688

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)0.0000.000

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 head0.014
GPT teacher head0.268
Teacher spread0.254 · 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.

The models applied no category: nothing in the taxonomy fit this work.
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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Citations3
Published2023
Admission routes1
Has abstractyes

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