Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Updated TRIMM-2 results.
Bibliographic record
Abstract
8003 Background: Tal is a T-cell redirecting bispecific antibody (BsAb) targeting G protein–coupled receptor family C group 5 member D. Dara is an anti-CD38 mAb with direct on-tumor and immunomodulatory actions. Combining immunomodulatory effects of tal + dara may lead to synergistic efficacy. Initial TRIMM-2 (NCT04108195) results showed that SC tal RP2Ds, 0.4 mg/kg QW or 0.8 mg/kg Q2W, + SC dara had promising efficacy and increased CD38+/CD8+ T cells and proinflammatory cytokines. We report updated results with additional pts and longer follow-up. Methods: Pts had MM, ≥3 prior lines of therapy (LOT; including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double refractory to a PI and IMiD, and had not received anti-CD38 therapy in ≤90 d. Pts received tal RP2Ds with step-up dosing + dara 1800 mg per approved schedule. AEs were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Responses were assessed per IMWG criteria. Results: As of Dec 12, 2022 (N = 65), median follow-up was 11.5 mo (range 1.0–27.3). Median age was 63 y (range 37–81); 18% of pts had high-risk cytogenetics; 25% had extramedullary plasmacytomas. Median prior LOT was 5 (range 2–16): 63% penta-drug exposed; 58% triple-class refractory. Prior treatments included anti-CD38 (88% [77% refractory]), anti-BCMA (54% [38%]), BsAb (25% [25%]), and anti-BCMA CAR-T (17% [2%]) therapy. All pts had ≥1 AE (grade [Gr] 3/4 78%), most commonly CRS (78%; all Gr 1/2), dysgeusia (75%), dry mouth (55%), anemia (52%), fatigue (45%), and skin exfoliation (45%). CRS had a median time to onset of 1 d after the most recent dose with median duration of 2 d. 63% of pts had infections (Gr 3/4 22%; Gr 5 3% [n = 2 pneumonia, possibly related to tal + dara]). 38% of pts had neutropenia (Gr 3/4 26%). 85% had postbaseline IgG < 500 mg/dL; of these, 32% received IVIg. ICANS occurred in 3 pts (5%; all Gr 1/2 and resolved in 1–2 d). ORR was 78% (66% ≥VGPR; 45% ≥CR) across RP2Ds (100% in anti-CD38 naïve pts), and responses deepened over time. In pts exposed/refractory to prior therapy, ORRs were 75%/76% for anti-CD38, 74%/64% for anti-BCMA, and 75%/75% for BsAb. Median time to first response was 1 mo (range 0.9–8.3); at 12 mo, 86% of responders (89% of pts with ≥CR) still had responses. At data cutoff, 84% of responders remain on therapy (83%/82% anti-CD38 exposed/refractory). mPFS was 19.4 mo; 12-mo PFS and OS rates were 76% and 93%, respectively. Conclusions: Steroid-sparing tal + dara showed deep and durable responses with promising mPFS in heavily pretreated pts with RRMM, including pts refractory to anti-CD38/BCMA and T-cell redirecting therapy, suggesting combined immunomodulatory actions can yield robust responses in pts with refractory disease. The safety profile was clinically manageable; no new signals were identified with longer follow-up.
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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 | 0.007 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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".