Abstract
Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed / refractory multiple myeloma
Blood, Vol.146(Supplement 1), pp.94-94
11/03/2025
DOI: 10.1182/blood-2025-94
Abstract
Introduction: The CARTITUDE-4 study (NCT04181827), which enrolled patients with lenalidomide-refractory multiple myeloma (MM) after 1–3 prior lines of therapy (pLOT), demonstrated a significant benefit of ciltacabtagene autoleucel (cilta-cel) over established triplet regimens. However, the benefit of cilta-cel for patients with standard-risk cytogenetics remains less defined. Here, we report outcomes in patients with standard-risk cytogenetics from the intent-to-treat and as-treated populations in CARTITUDE-4.
Methods: InCARTITUDE-4, patients randomized to the cilta-cel arm underwent apheresis and bridging treatment with either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd), followed by lymphodepletion therapy with cyclophosphamide and fludarabine, and then a single cilta-cel infusion. Progression-free survival (PFS) was assessed using a validated computerized algorithm. The intent-to-treat population included 208 patients; 32 patients progressed or died on bridging therapy, resulting in an as-treated population of 176 patients. Patients with high-risk cytogenetics, defined as del(17p), t(14;16), t(4;14), gain/amp(1q) (n=105), or with unknown cytogenetics (n=12), were excluded from the as-treated analysis. The 12-month minimal residual disease (MRD)-negative complete response (CR) was defined per the International Myeloma Working Group criteria as the proportion of participants with CR or better prior to and at 12 months (±3 months), achieving MRD-negative status at 12 months (+3 months) after cilta-cel infusion, as determined by next-generation sequencing (10-5), prior to progressive disease or subsequent anti-myeloma therapy. For the as-treated population, PFS rates were measured from the time of cilta-cel infusion.
Results: In CARTITUDE-4, in the intent-to-treat population, at a median follow-up of 33.6 months, patients with standard-risk cytogenetics had a 30-month PFS rate (95% CI) of 71.0% (58.8–80.2) in the cilta-cel arm (N=69) vs 43.2% (31.3–54.5) in the standard-of-care (SOC) arm (N=70). Patients with standard-risk cytogenetics in the as-treated population (n=59) had a 30-month PFS rate of 80.5% (95% CI, 67.2–88.8). In CARTITUDE-1 (NCT03548207), which evaluated cilta-cel in patients with heavily pretreated relapsed/refractory MM (RRMM; ≥3 pLOT), the 30-month PFS rate among patients with standard-risk cytogenetics (negative for del(17p), t(14;16), or t(4;14); n=68) was 59.9% (95% CI, 47.2–70.5). In the CARTITUDE-4 as-treated population with standard-risk cytogenetics, 8 PFS events occurred within 1 year and 4 PFS events beyond 1 year of cilta-cel infusion. Twenty-six patients achieved MRD-negative CR at 12 months after cilta-cel; 100.0% of these patients were progression free at 30 months. Fourteen patients were not evaluable for MRD due to: calibration failure (n=12), no sample availability for testing (n=1), or indeterminate results post baseline (n=1).
Conclusions: The PFS rate at 2.5 years for patients with standard-risk RRMM was higher in CARTITUDE-4 compared with CARTITUDE-1, supporting the use of cilta-cel as early as second line in the treatment course. In CARTITUDE-4 (as-treated population), 80.0% of patients with standard-risk cytogenetics were progression free and off treatment at 2.5 years. In patients with standard-risk disease who achieved MRD-negative CR at 1 year, this rate increased to 100.0%. The low rate of progression events in cilta-cel-treated patients with standard-risk cytogenetics shows the profound benefit of a single cilta-cel infusion in this population.
Details
- Title: Subtitle
- Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed / refractory multiple myeloma
- Creators
- Luciano Costa - University of Alabama at BirminghamAlbert Oriol - Institut Català d'OncologiaDominik Dytfeld - Poznan University of Medical SciencesSalomon Manier - Université de LillePeter Voorhees - Levine Cancer InstituteYi Lin - Mayo ClinicMyo Htut - City Of Hope National Medical CenterWilfried Roeloffzen - University Medical Center GroningenPhoebe Joy Ho - Royal Prince Alfred HospitalUrvi Shah - Cornell UniversityMan Zhao - IQVIAQuanlin Li - Johnson & JohnsonAgnes Balogh - Johnson & JohnsonKatherine Li - Johnson & JohnsonAna Slaughter - Johnson & JohnsonNina Benachour - Johnson & JohnsonCarolina Lonardi - Johnson & JohnsonArnab Ghosh - Johnson & JohnsonHuabin Sun - Johnson & JohnsonNikoletta Lendvai - Johnson & JohnsonTamar Lengil - Johnson & JohnsonNitin Patel - 490 BioTechMythili Koneru - 490 BioTechErika Florendo - 490 BioTechOctavio Costa - 490 BioTechVrinda Mahajan - 490 BioTechPaula Rodriguez-Otero - Clinica Universidad de NavarraChristopher Strouse - University of IowaKeith Stewart - Princess Margaret Cancer CentreSurbhi Sidana - Stanford University
- Resource Type
- Abstract
- Publication Details
- Blood, Vol.146(Supplement 1), pp.94-94
- DOI
- 10.1182/blood-2025-94
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/03/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985116167502771
Metrics
2 Record Views