Efficacy and safety of frail adults treated with ciltacabtagene autoleucel in the real-world: A CIBMTR analysis
Bibliographic record
Abstract
Abstract Background: Ciltacabtagene Autoleucel (Cilta-cel), an anti-BCMA CAR-T cell therapy, is approved for relapsed/refractory multiple myeloma (RRMM) based upon the results of several pivotal clinical trials. Frail adults are known to be under-represented in clinical trials. To ensure cilta-cel is effectively utilized in this subgroup, there is a need to understand both the efficacy and safety of cilta-cel among frail adults treated in the real-world. Methods: We conducted a retrospective cohort study of patients (pts) with RRMM treated with standard of care cilta-cel reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). Eligible pts had received ≥4 prior lines of therapy (LOT) between Mar 2022-Aug 2024 and completed a 100-day follow up form. Frailty was defined using the simplified frailty index (Facon et al., Leukemia, 2020), incorporating age, performance status, and comorbidities (hematopoietic cell transplantation specific comorbidity index score ≥2, 1 point). Pts with a frailty score ≥2 were classified as frail. Efficacy outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Safety outcomes included CRS, ICANS, prolonged cytopenia (>3 months), clinically significant infections, and treatment-related mortality (TRM). We used multivariable regression to assess the independent impact of frailty on outcomes, adjusting for key patient- and disease-related variables. Results: Among 595 treated pts, frailty status was available for 541, of whom 183 (33.8%) were categorized as frail and 358 (66.2%) as non-frail. Median ages were 65.5 years (range, 38 – 84; ≥70 years, 35%) in the frail group and 63 years (range, 34 -80; ≥70 years, 15.6%) in the non-frail group. Overall, median prior LOT were 7 (range 4–24), 25.1% pts had high-risk cytogenetics, and 7.6% had prior BCMA exposure with no statistically significant differences between frail and non-frail pts. At a median follow up of 12 months, the best ORR in the frail group was 82.9% versus 88.5% in non-frail pts. The 12-month PFS in frail pts was 62.7% (95% CI, 53.6-71.3%) versus 75.9% (95% CI, 70.4-81.1%) in non-frail adults (log-rank p<0.01). Similarly, the 12-month OS was 72.8% (95% CI, 64.9-80.0%) in the frail group versus 90.4% (95% CI, 86.6-93.7%) in non-frail pts (log-rank p<0.01). The 12-month TRM was 6.8% (95% CI, 3.4-11.2%) in frail pts versus 3.6% (95% CI, 1.8-6.1%) in non-frail pts (p=0.11). A total of 82 pts (15.2%) died during the follow up period (frail, n=45; non-frail, n=37). Progression was the most common cause of death in both groups (57.8% and 62.2%), followed by infections (13.3% and 8.1%). Two pts died from ICANS, and one pt died from CRS in the frail group. There were no ICANS-related deaths in the non frail group; one pt died from CRS. In terms of toxicity, 434 (80.2%) pts developed CRS, with grade 2+ CRS in 22.4% frail versus 17.9% of non-frail pts. A total of 141 patients (26.1%) developed neurotoxicity with rates of grade 2+ neurotoxicity being higher in frail (n=21, 11.5%) versus non-frail (n=18, 5%). More specifically, any-grade ICANS was noted in 32.2% of frail versus 17.6% non-frail pts. Cranial nerve palsies and parkinsonism developed among 2.6% and 2.8% of frail and non-frail pts. Rates of prolonged cytopenia were 30.6% in frail versus 21.2% in non-frail pts. Other toxicities including macrophage activation syndrome/hemophagocytic lymphohistiocytosis (3.7%) and clinically significant infections (47.0%) did not differ between frail and non-frail adults. A total of 23 pts (4.5%) developed a secondary malignancy, with no differences between frail and non-frail pts. After adjusting for patient- and disease-related factors in a multivariable model, frailty was not significantly associated with response or risk for CRS grade 2+. However, frail pts experienced significantly worse PFS (HR 1.67, 95% CI 1.16-2.40, p=0.0059) and OS (HR 2.46, 95% CI 1.57-3.87, p <0.0001). Additionally, frailty doubled the odds of developing any-grade ICANS (OR 2.01, 95% CI 1.32-3.08, p=0.0012). Conclusion: This study represents the largest cohort to-date examining outcomes of frail adults treated with cilta-cel. Frail pts experienced inferior survival and increased risk for ICANS compared to their non-frail counterparts. These findings highlight the urgent need for tailored CAR-T strategies and prospective studies focused on this vulnerable population
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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 | 0.004 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| 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 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".