PMID- 37405396
OWN - NLM
STAT- MEDLINE
DCOM- 20231107
LR  - 20240502
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 29
IP  - 21
DP  - 2023 Nov 1
TI  - FDA Approval Summary: Axicabtagene Ciloleucel for Second-Line Treatment of Large 
      B-Cell Lymphoma.
PG  - 4331-4337
LID - 10.1158/1078-0432.CCR-23-0568 [doi]
AB  - In April 2022, the FDA approved axicabtagene ciloleucel (axi-cel) for adults with 
      large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy 
      or that relapses within 12 months of first-line chemoimmunotherapy. Approval was 
      based on ZUMA-7, a randomized (1:1), open-label trial in 359 patients with 
      primary refractory LBCL (74%) or early relapse who were transplant candidates. 
      The study compared a single course of axi-cel to standard therapy, consisting of 
      chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic 
      stem cell transplantation (HSCT) in responding patients. Overall, 94% of the 
      experimental arm received chimeric antigen receptor (CAR) T-cell product, and 35% 
      of the control arm received on-protocol HSCT. The primary endpoint was event-free 
      survival, which was significantly longer in the axi-cel arm with an HR of 0.40 
      (95% confidence interval, 0.31-0.51; P value < 0.0001) and estimated median of 
      8.3 months, versus 2.0 months with standard therapy. Among 168 recipients of 
      axi-cel, cytokine release syndrome occurred in 92% (Grade >/= 3, 7%), neurologic 
      toxicity in 74% (Grade >/= 3, 25%), prolonged cytopenias in 33%, and fatal adverse 
      reactions in 1.8%. This is the first FDA approval of a CAR T-cell therapy for 
      LBCL in the second-line setting and reflects a potential paradigm shift.
CI  - (c)2023 American Association for Cancer Research.
FAU - Sharma, Poornima
AU  - Sharma P
AUID- ORCID: 0009-0009-0075-7939
AD  - Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 
      Silver Spring, Maryland.
FAU - Kasamon, Yvette L
AU  - Kasamon YL
AUID- ORCID: 0000-0002-4676-2559
AD  - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 
      Silver Spring, Maryland.
AD  - Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, 
      Maryland.
FAU - Lin, Xue
AU  - Lin X
AUID- ORCID: 0000-0002-3274-2645
AD  - Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 
      Silver Spring, Maryland.
FAU - Xu, Zhenzhen
AU  - Xu Z
AUID- ORCID: 0000-0002-8755-8597
AD  - Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 
      Silver Spring, Maryland.
FAU - Theoret, Marc R
AU  - Theoret MR
AUID- ORCID: 0000-0003-4973-5297
AD  - Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 
      Silver Spring, Maryland.
AD  - Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, 
      Maryland.
FAU - Purohit-Sheth, Tejashri
AU  - Purohit-Sheth T
AUID- ORCID: 0000-0003-3359-9673
AD  - Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 
      Silver Spring, Maryland.
LA  - eng
GR  - FD999999/ImFDA/Intramural FDA HHS/United States
GR  - FD/FDA HHS/United States
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antigens, CD19)
RN  - U2I8T43Y7R (axicabtagene ciloleucel)
RN  - 0 (Biological Products)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Antigens, CD19
MH  - *Biological Products/adverse effects/therapeutic use
MH  - Immunotherapy, Adoptive/methods
MH  - *Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Drug Approval
PMC - PMC10767767
MID - NIHMS1909878
COIS- Disclosure of Potential Conflicts of Interest: No potential conflicts of interest 
      were disclosed.
EDAT- 2023/07/05 13:05
MHDA- 2023/11/02 12:42
PMCR- 2024/05/01
CRDT- 2023/07/05 10:53
PHST- 2023/03/06 00:00 [received]
PHST- 2023/04/28 00:00 [revised]
PHST- 2023/06/15 00:00 [accepted]
PHST- 2023/11/02 12:42 [medline]
PHST- 2023/07/05 13:05 [pubmed]
PHST- 2023/07/05 10:53 [entrez]
PHST- 2024/05/01 00:00 [pmc-release]
AID - 727641 [pii]
AID - 10.1158/1078-0432.CCR-23-0568 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2023 Nov 1;29(21):4331-4337. doi: 10.1158/1078-0432.CCR-23-0568.