Luciano Costa MD PhD ASH 2025
Luciano Costa, MD, PhD; ASH 2025: CAR T Cell Brings Profound Benefit with Long-Term Progression-Free Survival in Patients with Standard-Risk Relapsed/Refractory Multiple Myeloma
An interview with:
Luciano Costa, MD PhD, University of Alabama at Birmingham, Birmingham, Alabama, United States
ORLANDO, USA—The CARTITUDE-4 study has f0und that patients with standard-risk relapsed or refractory multiple myeloma can benefit greatly from ciltacabtagene autoleucel CAR-T cell therapy after one to three prior lines of therapy, as do those with high-risk disease. Study findings were reported at the American Society of Hematology 2025 Annual Meeting in Orlando Florida by Luciano Costa, MD, PhD, University of Alabama, in Birmingham, Alabama, USA. After his talk at the conference he discussed the findings with the Audio Journal of Oncology reporter, Peter Goodwin:
AUDIO JOURNAL OF ONCOLOGY: Luciano Costa MD PhD
IN: [Goodwin] “I’m right here at the ……
OUT: …. In Orlando, Florida. 13:04 secs
JOURNAL ARTICLE:
Reference: Blood:
Volume 146, Supplement 1, 3 November 2025, Page 94
LINK:
https://www.sciencedirect.com/science/article/pii/S0006497125026692
TITLE:
Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed / refractory multiple myeloma
First author: Luciano Costa
Authors:
- University of Alabama at Birmingham, Birmingham, United StatesLuciano Costa 1, Albert Oriol 2, Dominik Dytfeld 3, Salomon Manier 4, Peter Voorhees 5,
Yi Lin 6, Myo Htut 7, Wilfried Roeloffzen 8, Phoebe Joy Ho 9, Urvi Shah 10, Man Zhao 11, Quanlin Li 12, Agnes Balogh 13, Katherine Li 14, Ana Slaughter 15, Nina Benachour 13, Carolina Lonardi 16, Arnab Ghosh 17, Huabin Sun 17, Nikoletta Lendvai 17, Tamar Lengil 17, Nitin Patel 18, Mythili Koneru 18, Erika Florendo 18, Octavio Costa 18, Vrinda Mahajan 18, Paula Rodriguez Otero 19, Christopher Strouse 20, Keith Stewart 21, Surbhi Sidana 22
Institutions:
1.University of Alabama at Birmingham, Birmingham, United States
2Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
3Poznan University of Medical Sciences, Poznań, Poland
4University of Lille, CHU Lille, Lille, France
5Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, United States
6Mayo Clinic, Rochester, United States
7Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, United States
8Department of Hematology, University Medical Center Groningen, Groningen, Netherlands
9Royal Prince Alfred Hospital, Sydney, Australia
10Myeloma Service, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, United States
11IQVIA, Shanghai, China
12Johnson & Johnson, Apex, United States
13Johnson & Johnson, Beerse, Belgium
14Johnson & Johnson, Spring House, United States
15Johnson & Johnson, Zug, Switzerland
16Johnson & Johnson, Buenos Aires, Argentina
17Johnson & Johnson, Raritan, United States
18Legend Biotech USA Inc, Somerset, United States
19Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain
20Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, United States
21University Health Network and the Princess Margaret Cancer Centre, Toronto, ON, Canada
22Stanford University School of Medicine, Stanford, United States
ASH Abstract Presentation ID 94
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.
Luciano Costa MD PhD AJO Text
January 14, 2026 Audio Journal of Oncology