P907: EFFICACY AND SAFETY OF ELRANATAMAB IN HIGH-RISK PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: A SUBGROUP ANALYSIS FROM MAGNETISMM-3
Bibliographic record
Abstract
Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Data from the ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM) and no prior BCMA-directed therapy (Cohort A). Aims: To report the efficacy and safety of elranatamab in high-risk subgroups in BCMA-naïve patients from MagnetisMM-3. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups analyzed were Revised International Staging System (R-ISS) stage (I/II/III), cytogenetic abnormalities (standard/high risk [high-risk defined by the presence of t(4;14), t(14;16) or del(17p)]), extramedullary disease (EMD) at baseline (Y/N), bone marrow plasma cell involvement (BMPC) at baseline (<50%/≥50%), and penta-refractory disease (Y/N). Results include data up through ~12 months after last patient initial dose. Results: Median treatment durations and the proportions of patients receiving treatment at the data cut-off were lower for all high-risk subgroups than the corresponding lower-risk subgroups (Table). The most frequent cause of discontinuation was progressive disease which was higher for all high-risk subgroups than the corresponding lower risk subgroups. A clinical benefit, assessed by the objective response rate (ORR), was observed across subgroups (Table). A multivariable logistic regression analysis for ORR including baseline age, Eastern Cooperative Oncology Group, sex, region, cytogenetic risk, presence of EMD, BMPC involvement, prior stem cell transplant, R-ISS stage, number of prior lines, type of myeloma, and penta-refractory disease showed presence of EMD at baseline and non-IgG myeloma (vs IgG) as predictive of lower ORR. Light chain-only myeloma (vs IgG) was predictive of higher ORR. Median duration of response (DOR) was not reached in subgroups by 12 months, DOR rate at 12 months is reported in the Table. Any-grade treatment-emergent adverse events (TEAEs) were reported in 100% of patients in the study. The incidence of grade 3/4 TEAEs was overall similar across subgroups (Table). Summary/Conclusion: Elranatamab is efficacious and has a manageable safety profile in patients with high-risk RRMM and no prior BCMA-directed therapy. Table - R-ISS stage I R-ISS stage II R-ISS stage III Standard cytogenetic risk High cytogenetic risk (n=28) (n=68) (n=19) (n=83) (n=31) Median treatment duration (mo) 10.7 5.7 1.4 7.9 2.6 Receiving treatment at data cut-off (%) 42.9 38.2 5.3 41.0 19.4 ORR (%, 95% CI) 75.0 63.2 26.3 63.9 54.8 (55.1, 89.3) (50.7, 74.6) (9.1, 51.2) (52.6, 74.1) (36.0, 72.7) DOR rate at 12 mo (%, 95% CI) 76.2 78.8 53.3 79.4 57.0 (45.4, 91.0) (61.8, 88.8) (6.8, 86.3) (63.4, 89.0) (27.4, 78.3) Grade 3/4 TEAEs (%) 75.0 73.5 63.2 73.5 64.5 - EMD – N EMD – Y <50% BMPC ≥50% BMPC Penta-refractory disease – N Penta-refractory disease - Y (n=84) (n=39) (n=89) (n=26) (n=71) (n=52) Median treatment duration (mo) 8.4 2.2 8.2 3.0 10.0 2.3 Receiving treatment at data cut-off (%) 38.1 25.6 38.2 26.9 42.3 23.1 ORR (%, 95% CI) 71.4 38.5 67.4 46.2 71.8 46.2 (60.5, 80.8) (23.4, 55.4) (56.7, 77.0) (26.6, 66.6) (59.9, 81.9) (32.2, 60.5) DOR rate at 12 mo (%, 95% CI) 73.8 73.4 72.0 81.5 74.7 71.9 (58.3, 84.3) (37.4, 90.8) (56.6, 82.7) (43.5, 95.1) (58.6, 85.3) (41.2, 88.4) Grade 3/4 TEAEs (%) 77.4 56.4 73.0 69.2 73.2 67.3 Keywords: Myeloma, Bispecific, Multiple myeloma, Clinical trial
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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 teacher head, 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".