TY  - CHAP
M1  - Book, Section
TI  - A Patient with Ureteric Transitional Cell Carcinoma on Anti-PD-1 Antibody Complicated by Sarcoidosis
A1  - Spiliopoulou, Pavlina
A1  - Jones, Rob J.
A2  - Board, Ruth E.
A2  - Nathan, Paul
A2  - Newsom-Davis, Tom
A2  - Papa, Sophie
A2  - Johnson, Peter
PY  - 2019
T2  - Problem Solving in Cancer Immunotherapy
AB  - A  79-year-old  man  was  found  to  have  thickening  of  the  right  ureter  during  staging  investigations  for  a  Dukes'  A  rectal  adenocarcinoma.  Ureteroscopy  revealed  a  grade  3  transitional  cell  carcinoma  of  the  distal  right  ureter  as  well  as  a  suspicious  lung  nodule.  The  primary  ureteric  tumour  was  deemed  inoperable  and  the  patient  was  referred  to  oncology  for  consideration  of  systemic  treatment.  His  medical  history  consisted  of  chronic  obstructive  pulmonary  disease,  osteoarthritis  and  hypertension.  He  had  a  right-sided  ureteric  stent  in  situ  with  established  right  kidney  cortical  atrophy  and  borderline  creatinine  clearance.He  was  not  considered  suitable  for  cisplatin-based  chemotherapy  (the  current  standard  of  care  for  advanced  urothelial  cancer);  he  therefore  received  six  cycles  of  carboplatin/gemcitabine,  with  partial  response.  Fifteen  months  later  he  developed  progressive  metastasis  in  the  upper  lobe  of  the  right  lung.  He  entered  an  early  phase  clinical  trial  with  the  anti-programmed  cell  death  protein  1  (PD-1)  antibody  nivolumab.Early  in  the  treatment  he  developed  grade  1  pruritus,  managed  with  topical  steroids,  and  a  grade  3  asymptomatic  amylase  rise  that  subsequently  resolved  without  intervention.  His  disease  remained  stable  for  10  months,  when  a  CT  scan  revealed  evolving  mediastinal  and  abdominal  lymphadenopathy.  In  the  absence  of  new  clinical  findings  and/or  unacceptable  toxicity,  treatment  was  continued  based  on  the  possibility  that  the  new  lymphadenopathy  could  be  attributed  to  pseudo-progression.  At  the  same  time  he  complained  of  small  joint  arthralgia  in  both  hands,  which  was  adequately  managed  with  analgesia.Over  the  next  18  months  the  size  of  mediastinal  and  abdominal  lymphadenopathy  fluctuated  by  a  few  millimetres,  while  the  primary  tumour  remained  stable  throughout;  the  anti-PD-1  antibody  was  continued.  Twenty-eight  months  after  starting  treatment  the  patient  presented  with  an  eruption  of  a  pruritic,  scaly  rash  on  his  arms  and  legs  with  purple  plaques  on  his  back  (Figure  19.1).  A  skin  biopsy  was  obtained  but,  before  the  results  were  available,  he  was  admitted  with  symptomatic  hypercalcaemia  (corrected  calcium  3  mmol/l  [normal  range  2.20–2.60  mmol/l]).  The  biopsy  results  showed  granulomatous  dermatitis  in  the  superficial  dermis  with  negative  stains  for  mycobacteria  and  negative  stains  for  fungal  infection.  The  changes  were  pathognomonic  of  cutaneous  sarcoidosis.  CT  imaging  of  the  chest  showed  reticulonodular  lung  parenchymal  changes  consistent  with  interstitial  lung  disease  (Figure  19.2).The  combination  of  interstitial  lung  changes,  cutaneous  sarcoidosis  and  hypercalcaemia  established  the  diagnosis  of  systemic  sarcoidosis.  All  changes  resolved  with  the  withdrawal  of  nivolumab;  the  patient's  cancer  remained  stable  when  last  seen  6  months  after  discontinuation  of  immunotherapy.On  what  basis  was  the  patient  deemed  unsuitable  for  first  line  cisplatin-based  chemotherapy,  and  what  is  the  evidence  behind  the  use  of  platinum/gemcitabine  in  urothelial  cancer?What  is  the  role  of  nivolumab  and  other  immunotherapeutic  agents  in  the  second  line  treatment  of  urothelial  cancer?What  are  the  commonest  toxicities  associated  with  anti-PD-1  antibodies,  and  what  is  the  mainstay  of  their  treatment?How  common  is  sarcoidosis  with  anti-PD-1  treatment,  and  how  does  it  present?  
SN  - 
PB  - EBN Health
CY  - New York, NY
Y2  - 2021/03/06
UR  - hemonc.mhmedical.com/content.aspx?aid=1160633461
ER  -