Outcomes of Cilta-Cel Manufacturing for Lenalidomide-Refractory Multiple Myeloma Strongly Influenced by Prior Lines of Therapy
Key Clinical Summary
- Population and Design: Real-world analysis of ~3,000 commercial manufacturing cases evaluated how prior lines of therapy (pLOTs) affect ciltacabtagene autoleucel (cilta-cel) production outcomes in relapsed/refractory (R/R) multiple myeloma (MM).
- Findings: First-attempt manufacturing success was 93% in patients with ≥1 prior line vs 89% in those with ≥ 4; CD4:CD8 ratio improved by 54% (1.0 vs 0.65) with fewer prior therapies. Among 317 out-of-specification (OOS) cases, 63% were released under expanded access, 28.6% required remanufacturing, and only 40% achieved in-specification results; repeated OOS or cancellation occurred in 67% of heavily pretreated patients.
- Clinical Relevance: Earlier use of cilta-cel (fewer prior therapies) leads to higher manufacturing reliability and cell quality, while remanufacturing after multiple prior lines often results in delays or OOS outcomes, underscoring the importance of timely patient selection and collection for CAR T-cell therapy.
According to research presented by Robert Bowden, MD, Janssen Research and Development, Spring House, Pennsylvania, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida, the success of ciltacabtagene autoleucel manufacturing for patients with lenalidomide-refractory multiple myeloma (MM) as early as first relapse decreases with increased prior lines of therapies, according to research presented at the 2025 ASH Annual Meeting & Exposition.
In a large real-world analysis of commercial manufacturing data, investigators found that prior lines of therapy (pLOTs) significantly influence the success rates of ciltacabtagene autoleucel (cilta-cel) manufacturing, with better outcomes observed in patients with fewer prior treatments. These findings were presented in the context of cilta-cel's use for relapsed/refractory (R/R) multiple myeloma (MM), where variability in patient-derived T cells continues to pose a challenge to consistent CAR-T cell product manufacturing.
Researchers conducted a large real-world analysis of commercial manufacturing data of ciltacabtagene autoleucel to evaluate the impact of prior lines of therapy on patient outcomes. Among the 3,000 patients analyzed, first-time manufacturing success for cilta-cel was 93% for patients with ≥1 prior lines of therapy compared to 89% among patients with ≥4 prior lines of therapy. Initial CD4:CD8 ratio was improved by 54% among patients with fewer prior lines of therapy (1.0 with 1 prior line vs 0.65 ≥ 4 prior lines).
Researchers identified 317 out-of-specification (OOS) manufacturing cases. Approximately 63% of cases were released via expanded access without remanufacturing and 28.6% underwent remanufacturing, however, only 40% achieved in-specification products. Remanufacturing among patients with ≥4 prior lines of therapy resulted in repeated OOS or cancellation in 67% of cases. Attempts to recollect new apheresis material led to similar or worse outcomes in 31% of cases, with 20% ultimately canceled.
Overall, final product success improved to 99% in patients with ≥1 prior line compared to 97% in those with ≥4 prior lines.
The researchers concluded, “Rates of first and overall manufacturing success were higher when using cells collected from patients with ≥ 1 versus ≥ 4 pLOTs.”
They added, “Remanufacture of product often results in additional OOS outcomes, which may further delay patient treatment.”
Source:
Bowden R, Araque J, Choudhary G, et al. Ciltacabtagene autoleucel out-of-specification manufacturing outcomes improve with earlier lines of therapy. Dec 6-9, 2025; Orlando, FL. Abstract: 2411
