PMID- 32822484
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20211204
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 4
IP  - 16
DP  - 2020 Aug 25
TI  - Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel 
      in large B-cell lymphoma.
PG  - 3943-3951
LID - 10.1182/bloodadvances.2020002228 [doi]
AB  - Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) 
      is the second most common acute toxicity after chimeric antigen receptor (CAR) 
      T-cell therapy. However, there are limited data on the clinical and radiologic 
      correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients 
      with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of 
      care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an 
      objective grading system. Neuroimaging studies and electroencephalograms (EEGs) 
      were reviewed by an expert neuroradiologist and neurologist. Of 100 patients 
      included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had 
      grade >/=3. Median time to ICANS onset was 5 days, and median duration was 6 days. 
      ICANS grade >/=3 was associated with high peak ferritin (P = .03) and C-reactive 
      protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 
      days after axi-cel infusion. Magnetic resonance imaging was performed in 38 
      patients with ICANS and revealed 4 imaging patterns with features of encephalitis 
      (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible 
      encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse 
      slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status 
      epilepticus (n = 8). Although reversible, grade >/=3 ICANS was associated with 
      significantly shorter progression-free (P = .02) and overall survival 
      (progression being the most common cause of death; P = .001). Our results suggest 
      that imaging and EEG abnormalities are common in patients with ICANS, and 
      high-grade ICANS is associated with worse outcome after CAR T-cell therapy in 
      LBCL patients.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Strati, Paolo
AU  - Strati P
AD  - Department of Lymphoma and Myeloma.
FAU - Nastoupil, Loretta J
AU  - Nastoupil LJ
AD  - Department of Lymphoma and Myeloma.
FAU - Westin, Jason
AU  - Westin J
AD  - Department of Lymphoma and Myeloma.
FAU - Fayad, Luis E
AU  - Fayad LE
AD  - Department of Lymphoma and Myeloma.
FAU - Ahmed, Sairah
AU  - Ahmed S
AD  - Department of Lymphoma and Myeloma.
AD  - Department of Stem Cell Transplantation and Cellular Therapy.
FAU - Fowler, Nathan H
AU  - Fowler NH
AD  - Department of Lymphoma and Myeloma.
FAU - Hagemeister, Fredrick B
AU  - Hagemeister FB
AD  - Department of Lymphoma and Myeloma.
FAU - Lee, Hun J
AU  - Lee HJ
AD  - Department of Lymphoma and Myeloma.
FAU - Iyer, Swaminathan P
AU  - Iyer SP
AD  - Department of Lymphoma and Myeloma.
FAU - Nair, Ranjit
AU  - Nair R
AD  - Department of Lymphoma and Myeloma.
FAU - Parmar, Simrit
AU  - Parmar S
AD  - Department of Lymphoma and Myeloma.
FAU - Rodriguez, Maria A
AU  - Rodriguez MA
AD  - Department of Lymphoma and Myeloma.
FAU - Samaniego, Felipe
AU  - Samaniego F
AD  - Department of Lymphoma and Myeloma.
FAU - Steiner, Raphael E
AU  - Steiner RE
AD  - Department of Lymphoma and Myeloma.
FAU - Wang, Michael
AU  - Wang M
AD  - Department of Lymphoma and Myeloma.
FAU - Pinnix, Chelsea C
AU  - Pinnix CC
AD  - Department of Radiation Oncology.
FAU - Adkins, Sherry
AU  - Adkins S
AD  - Department of Lymphoma and Myeloma.
FAU - Claussen, Catherine M
AU  - Claussen CM
AD  - Department of Lymphoma and Myeloma.
FAU - Martinez, Charles S
AU  - Martinez CS
AD  - Department of Stem Cell Transplantation and Cellular Therapy.
FAU - Hawkins, Misha C
AU  - Hawkins MC
AD  - Department of Lymphoma and Myeloma.
FAU - Johnson, Nicole A
AU  - Johnson NA
AD  - Department of Lymphoma and Myeloma.
FAU - Singh, Prachee
AU  - Singh P
AD  - Department of Lymphoma and Myeloma.
FAU - Mistry, Haleigh E
AU  - Mistry HE
AD  - Department of Lymphoma and Myeloma.
FAU - Horowitz, Sandra
AU  - Horowitz S
AD  - Department of Lymphoma and Myeloma.
FAU - George, Shirley
AU  - George S
AD  - Department of Lymphoma and Myeloma.
FAU - Feng, Lei
AU  - Feng L
AD  - Department of Biostatistics.
FAU - Kebriaei, Partow
AU  - Kebriaei P
AD  - Department of Stem Cell Transplantation and Cellular Therapy.
FAU - Shpall, Elizabeth J
AU  - Shpall EJ
AD  - Department of Stem Cell Transplantation and Cellular Therapy.
FAU - Neelapu, Sattva S
AU  - Neelapu SS
AD  - Department of Lymphoma and Myeloma.
FAU - Tummala, Sudhakar
AU  - Tummala S
AD  - Department of Neuro-oncology, and.
FAU - Chi, T Linda
AU  - Chi TL
AD  - Department of Neuro-Radiology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Antigens, CD19)
RN  - 0 (Biological Products)
RN  - U2I8T43Y7R (axicabtagene ciloleucel)
SB  - IM
MH  - Antigens, CD19/therapeutic use
MH  - Biological Products
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - *Neurotoxicity Syndromes/diagnostic imaging/etiology
MH  - *Posterior Leukoencephalopathy Syndrome
PMC - PMC7448589
COIS- Conflict-of-interest disclosure: L.J.N. reports honoraria from Celgene, 
      Genentech, Gilead, Janssen, Juno, Novartis, Spectrum, and TG Therapeutics and 
      research support from Celgene, Genentech, Janssen, Karus Therapeutics, and Merck. 
      N.H.F. reports honoraria from Celgene, Gilead Sciences, Pharmacyclics, and Roche 
      Pharma AG; research support from Celgene, Gilead Sciences, Pharmacyclics, and 
      Roche Pharma AG; and served as advisory board member for Novartis and Gilead 
      Sciences. M.C.H. served as advisory board member for Novartis. F.S. reports 
      honoraria from Celgene. S.S.N. has received research support from Kite/Gilead, 
      Cellectis, Poseida, Merck, Acerta, Karus, Bristol-Myers Squibb, Unum 
      Therapeutics, Allogene, and Precision Biosciences; served as consultant and 
      advisory board member for Kite/Gilead, Celgene, Novartis, Bristol-Myers Squibb, 
      Unum Therapeutics, Pfizer, Merck, Precision Biosciences, Cell Medica, Incyte, 
      Allogene, Calibr, and Legend Biotech; and has patents related to cell therapy. 
      The remaining authors declare no competing financial interests.
EDAT- 2020/08/22 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/08/21
CRDT- 2020/08/22 06:00
PHST- 2020/05/04 00:00 [received]
PHST- 2020/07/13 00:00 [accepted]
PHST- 2020/08/22 06:00 [entrez]
PHST- 2020/08/22 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/08/21 00:00 [pmc-release]
AID - S2473-9529(20)31154-X [pii]
AID - 2020/ADV2020002228 [pii]
AID - 10.1182/bloodadvances.2020002228 [doi]
PST - ppublish
SO  - Blood Adv. 2020 Aug 25;4(16):3943-3951. doi: 10.1182/bloodadvances.2020002228.