Molecular features and outcomes for patients receiving elranatamab for relapsed or refractory multiple myeloma in MagnetisMM-1.
Bibliographic record
Abstract
e20021 Background: Multiple myeloma (MM) is a plasma cell dyscrasia that expresses B-cell maturation antigen (BCMA). Elranatamab (PF-06863135), a BCMA x CD3 bispecific antibody, redirects the T-cell mediated immune response against MM. MagnetisMM-1 (NCT03269136) is the Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of elranatamab for patients (pts) with relapsed or refractory MM. Methods: Elranatamab was given subcutaneously at doses 80–1000 µg/kg weekly or every 2 weeks. Treatment-emergent adverse events (TEAEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events (v4.03), whereas cytokine release syndrome (CRS) was assessed by criteria of American Society for Transplantation and Cellular Therapy. PK and cytokines were analyzed over time. Bone marrow aspirates were used for cytogenetic analysis, whole exome sequencing, and minimal residual disease (MRD). Clinical response and MRD (with sensitivity of 1×10-5 by next generation sequencing) were assessed by International Myeloma Working Group criteria. Results: 55 pts received elranatamab at efficacious doses ≥215 μg/kg as of September 30, 2022. Pts had median age of 64 years (range 42-80), median of 5 prior regimens (range 2-14), 91% were triple-class refractory, 29% had high cytogenetic risk, and 24% received prior BCMA-targeted therapy. The most common TEAEs included CRS, injection site reaction, neutropenia, anemia, lymphopenia, and thrombocytopenia. Premedication and 1-step priming mitigated CRS. Elranatamab showed linear PK. Genetic alterations potentially relevant to molecular pathogenesis of MM were identified and included functional mutations in KRAS, NRAS, and TP53. With median follow-up of 12.0 months (range 0.3-32.3), objective response rate (ORR) was 64% (95% CI 50-75%) with 56% of pts (31/55) achieving very good partial response (VGPR) or better and 38% of pts (21/55) achieving complete response (CR) or better. Among 13 pts with prior BCMA-targeted therapy, 54% (7/13) achieved response including 46% (6/13) with VGPR or better. All 13 MRD-evaluable pts with confirmed CR or better and dominant clone sequence at baseline achieved MRD negativity, including 2 patients with ongoing stringent CR beyond 2 years. Median duration of response (DOR) was 17.1 months (n = 35; 95% CI 11.1-NE). Median progression-free survival (PFS) was 11.8 months (n = 55; 95% CI 6.0-19.1), and median overall survival (OS) was 21.2 months (n = 55; 95% CI 10.9-NE). Conclusions: Elranatamab induced durable clinical and molecular responses with an acceptable safety profile for pts with relapsed or refractory MM. The ORR was 64% with more than half of these pts (38%) achieving CR or better, and 100% of evaluable pts achieved MRD negativity. These results, along with emerging evidence for both PFS and OS, support the clinical activity of elranatamab for pts with MM. Clinical trial information: NCT03269136 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".