S195: IDECABTAGENE VICLEUCEL (IDE-CEL) VS STANDARD REGIMENS IN PATIENTS WITH TRIPLE-CLASS–EXPOSED (TCE) RELAPSED AND REFRACTORY MULTIPLE MYELOMA (RRMM): A KARMMA-3 ANALYSIS IN HIGH-RISK SUBGROUPS
Bibliographic record
Abstract
Background: Despite improvements in the treatment landscape of RRMM with the use of combination therapy, with immunomodulatory (IMiD®) agents, proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies in front-line and early relapse, patients are becoming TCE earlier in their treatment course. Outcomes in patients with high-risk disease characteristics such as cytogenetic abnormalities, advanced-disease stage, high tumor burden, presence of extramedullary plasmacytoma (EMP), and triple-class–refractory (TCR) disease also remain poor. Ide-cel, a BCMA-directed CAR T cell therapy, significantly improved median progression-free survival (mPFS; 13.3 vs 4.4 months [mo]; HR, 0.49; P<0.0001) and overall response rates (ORR; 71 vs 42%, P<0.001) vs standard (std) regimens in the overall population of patients with TCE RRMM in KarMMa-3 (NCT03651128; Rodríguez-Otero NEJM 2023; DOI: 10.1056/NEJMoa2213614). Aims: To assess the efficacy and safety of ide-cel vs std regimens in patients with high-risk disease characteristics in KarMMa-3. Methods: In KarMMa-3, patients with RRMM who received 2–4 prior regimens, who were TCE (IMiD agent, PI, and daratumumab), and had disease refractory to the last regimen, were randomized 2:1 to receive ide-cel (target dose range: 150–450 x 106 CAR+ T cells) or a std regimen (DPd, DVd, IRd, Kd, or EPd, based on prior regimen, per investigator). Efficacy (PFS, ORR, and complete response rate [CRR]) was assessed in high-risk groups including patients with cytogenetic abnormalities (del[17p], t[4;14], or t[14;16]), R-ISS stage III disease, high tumor burden (≥50% CD138-positive plasma cells in bone marrow), EMP (soft-tissue–only and soft-tissue bone-related plasmacytomas), and TCR (refractory to ≥1 each of an IMiD agent, a PI, and an anti-CD38 antibody). Results: Baseline demographics and high-risk disease characteristics were balanced between treatment arms. Median time to progression on the last prior regimen was short in patients treated with both ide-cel vs std regimens in all high-risk subgroups: cytogenetic abnormalities (5.6 vs 6.7 mo), R-ISS stage III disease (3.9 vs 3.5 mo), high tumor burden (5.1 vs 6.2 mo), EMP (5.1 vs 5.1 mo), and TCR disease (5.6 vs 5.8 mo). At a median follow-up of 18.6 mo (range, 0.4–35.4), mPFS was longer in patients treated with ide-cel vs std regimens in all high-risk subgroups: cytogenetic abnormalities (11.9 vs 4.2 mo; HR, 0.608), R-ISS stage III disease (5.2 vs 3.0 mo; HR, 0.861), high tumor burden (11.0 vs 4.9 mo; HR, 0.595), EMP (7.2 vs 2.0 mo; HR, 0.401), and TCR disease (11.2 vs 3.5 mo; HR, 0.458; Table). ORRs were improved with ide-cel vs std regimens, regardless of the presence of high-risk disease characteristics. Similarly, CRRs were improved in patients treated with ide-cel vs std regimens in all high-risk subgroups: cytogenetic abnormalities (31.8 vs 4.9%), R-ISS stage III (16.1 vs 7.1%), high tumor burden (31.0 vs 8.8%), EMP (23.0 vs 3.1%), and TCR disease (33.5 vs 1.1%). Safety data will be presented. Summary/Conclusion: Patients treated with ide-cel had a lower risk of disease progression or death and higher odds of achieving an overall response (with higher CRRs) compared with patients who received std regimens, regardless of baseline high-risk disease. Overall, these results support use of ide-cel in patients with TCE RRMM, including patients with difficult-to-treat, high-risk disease.Keywords: Clinical trial, Multiple myeloma, High risk, CAR-T
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.005 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 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".