RT Book, Section
A1 Tinsley, Nadina
A1 Board, Ruth E.
A2 Young, Alison
A2 Board, Ruth E.
A2 Leonard, Pauline
A2 Cooksley, Tim
A2 Stewart, Andrew
A2 Michie, Caroline
SR Print(0)
ID 1167764111
T1 Metastatic Melanoma with Rash and Diarrhoea after Treatment with Immune Checkpoint Inhibitors
T2 Problem Solving in Acute Oncology, 2e
YR 2020
FD 2020
PB Association of Cancer Physicians
PP New York, NY
SN 9780995595439
LK hemonc.mhmedical.com/content.aspx?aid=1167764111
RD 2021/03/05
AB A  45-year-old  woman  presented  with  a  history  of  right-sided  palpable  inguinal  lymphadenopathy.  Her  medical  history  included  malignant  superficial  spreading  melanoma,  0.8  mm,  pT1a,  excised  from  her  chest  wall  14  years  previously.  Fine  needle  aspiration  of  the  inguinal  lymph  node  revealed  metastatic  melanoma.  A  staging  PET  scan  showed  disseminated  malignancy  with  cutaneous  deposits  and  pulmonary  and  hepatic  metastases.  The  tumour  was  BRAF  V600E-positive  on  pyrosequencing  assay.Options  for  treatment  were  discussed  including  serine/threonine-protein  kinase  B-Raf  (BRAF)  inhibition  and  therapy  with  immune  checkpoint  inhibitors  (ICPIs),  either  single-agent  anti-programmed  cell  death  protein  1  (PD-1)  or  combination  anti-PD-1/cytotoxic  T  lymphocyte-associated  protein  4  (CTLA-4).  She  commenced  combination  ICPIs  with  3  weekly  ipilimumab  3  mg/kg  and  nivolumab  1  mg/kg,  planned  for  four  cycles,  as  tolerated.  The  goal  of  treatment  was  palliative:  improve  survival,  control  symptoms  and  preserve  functional  status.Following  the  first  ICPI  cycle,  she  developed  a  grade  2  pruritic  rash  and  grade  2  diarrhoea.  Examination  revealed  an  excoriated  erythematous  macular-papular  rash  affecting  her  trunk.  Stool  cultures  were  negative  and  immune-related  diarrhoea  was  diagnosed.  She  was  commenced  on  prednisolone  0.5  mg/kg  per  day  for  5  days.  Her  symptoms  resolved  and  the  steroids  were  weaned.  She  proceeded  to  have  her  next  treatment  cycle  after  2  weeks’  dose  interruption.Following  the  second  ICPI  cycle,  she  developed  grade  3  watery  diarrhoea.  Following  initial  assessment  in  the  acute  oncology  ‘hot  clinic’,  she  was  restarted  on  oral  steroids  for  immune-related  diarrhoea.  On  this  occasion,  the  diarrhoea  did  not  settle  after  3  days  of  oral  steroids  and  she  was  admitted  to  the  oncology  ward.  She  was  treated  for  immune-related  colitis  and  responded  well  to  3  days  of  intravenous  hydrocortisone  200  mg  three  times  daily.  She  did  not  require  second-line  immunosuppressive  treatment.  She  was  discharged  on  a  reducing  course  of  oral  prednisolone.  A  restaging  CT  scan  confirmed  disease  response  with  resolution  of  pulmonary  nodules,  reduction  in  the  size  of  the  liver  lesions  and  marked  regression  in  the  subcutaneous  deposits.  She  continued  on  treatment  with  single-agent  nivolumab  480  mg  every  4  weeks  with  continued  response  and  no  further  toxicities.What  were  the  key  toxicities  in  this  case  and  how  were  they  identified  and  investigated?What  are  the  principles  of  treatment?What  other  gastrointestinal  manifestations  of  immune-related  toxicities  are  reported?Who  is  at  risk  of  immune-mediated  toxicities?