Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma.
Bibliographic record
Abstract
7540 Background: Teclistamab, the first approved B-cell maturation antigen × CD3 bispecific antibody (BsAb) with weight-based dosing for the treatment of patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM), demonstrated rapid, deep, and durable responses in the pivotal MajesTEC-1 study. Here, we report updated results from MajesTEC-1. Methods: Eligible pts received teclistamab at the recommended phase 2 dose (RP2D; 1.5 mg/kg subcutaneous QW preceded by step-up dosing) with the option to switch to Q2W dosing if a partial response or better after ≥4 cycles of therapy (phase 1) or complete response or better (≥CR) for ≥6 mo (phase 2) was achieved; pts not in ≥CR could switch due to adverse events (AEs). Pts could subsequently switch to less frequent dosing if they continued to demonstrate a response. The primary endpoint was overall response rate (ORR) assessed by independent review committee per International Myeloma Working Group 2016 criteria. AEs were graded per Common Terminology Criteria for Adverse Events v4.03. Cytokine release syndrome (CRS) was graded per American Society for Transplantation and Cellular Therapy guidelines. Results: At median follow-up of 30.4 mo, 165 pts had received teclistamab at the RP2D. ORR was 63.0%, and responses continued to deepen, with 46.1% achieving ≥CR. 85.7% (48/56) of MRD-evaluable pts were MRD negative (10 -5 threshold). Median duration of response (mDOR) increased to 24.0 mo; median progression-free survival (mPFS) and overall survival (mOS) improved to 11.4 and 22.2 mo, respectively. For pts with ≥CR, mDOR, mPFS, and mOS were not yet reached, and estimated 30-mo DOR, PFS, and OS rates were 60.8%, 61.0%, and 74.2%, respectively. Of the 38 pts who remain on treatment, 37 have switched to a less frequent dosing schedule (eg, Q2W), all of whom maintained responses. Hematologic AEs (any grade/grade 3/4) included neutropenia (72%/65%), anemia (55%/38%), thrombocytopenia (42%/23%), and lymphopenia (36%/35%). Infections occurred in 79% of pts (55% grade 3/4). Of grade 5 infections, 18/22 were due to COVID-19, reflecting study conduct during the COVID-19 pandemic. Onset of new grade ≥3 infections generally decreased over time, which aligned approximately with the median time of switch to Q2W dosing; other factors, such as increasing use of IVIG, may also contribute to this trend. AEs leading to dose reduction (n=1) or discontinuation (n=8; 5 due to infection) were infrequent. No new safety signals were reported. Conclusions: With the longest follow-up of any BsAb in MM, teclistamab continues to demonstrate deep and durable responses, including in pts who switch to less frequent dosing. The safety profile of teclistamab remains consistent with that of BCMA-targeted bispecific therapies, with a notable decrease in new onset of severe infections with time. Clinical trial information: NCT03145181 / NCT04557098 .
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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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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".