TY - JOUR
T1 - Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma
T2 - Results From the US Lymphoma CAR T Consortium
AU - Jain, Michael D.
AU - Spiegel, Jay Y.
AU - Nastoupil, Loretta J.
AU - Tamaresis, John
AU - Ghobadi, Armin
AU - Lin, Yi
AU - Lekakis, Lazaros
AU - Reagan, Patrick
AU - Oluwole, Olalekan
AU - Mcguirk, Joseph
AU - Deol, Abhinav
AU - Dorritie, Kathleen A.
AU - Sehgal, Alison R.
AU - Goy, Andre
AU - Hill, Brian T.
AU - Andreadis, Charalambos
AU - Munoz, Javier
AU - Ulrickson, Matthew
AU - Westin, Jason
AU - Chavez, Julio C.
AU - Patel, Dilan
AU - Jacobs, Miriam T.
AU - Bansal, Radhika
AU - Bennani, N. Nora
AU - Patel, Vivek G.
AU - Rapoport, Aaron P.
AU - Vose, Julie M.
AU - Miklos, David B.
AU - Neelapu, Sattva S.
AU - Locke, Frederick L.
AU - Lunning, Matthew
AU - Dahiya, Saurabh
N1 - Publisher Copyright:
© 2024 American Society of Clinical Oncology.
PY - 2024/10/20
Y1 - 2024/10/20
N2 - PURPOSE Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. METHODSWe previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. RESULTS Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P =.02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P <.001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). CONCLUSION In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.
AB - PURPOSE Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. METHODSWe previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. RESULTS Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P =.02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P <.001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). CONCLUSION In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.
UR - http://www.scopus.com/inward/record.url?scp=85205886902&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.02786
DO - 10.1200/JCO.23.02786
M3 - Article
C2 - 39094076
AN - SCOPUS:85205886902
SN - 0732-183X
VL - 42
SP - 3581
EP - 3592
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -