IMMUNE CHECK POINT INHIBITOR AND ANTHRACYCLINE INDUCED ATYPICAL HAEMOLYTIC URAEMIC SYNDROME
Dr TAREN BETTLER1,2, Dr TRISTAN A BARNES5, Dr JASVEEN RENTHAWA4, Dr GAJAN KAILAINATHAN3, Dr MOSES WAVAMUNNO1, Dr KATIE TRINH1, Dr KATRINA CHAU1,2
1Western Renal Services, WSLHD, Sydney, Australia, 2School of Medicine, Western Sydney University, Sydney, Australia, 3Cancer and Haematology Centre, Blacktown Hospital, Sydney, Australia, 4 Dept. of Tissue Pathology & Diagnostic Oncology, ICPMR Westmead, NSW Health Pathology, Sydney, Australia, 5Department of Oncology, North Shore Private Hospital, Sydney, Australia
Background: Immune checkpoint inhibitors (ICI) have been reported to cause acute interstitial nephritis and thrombotic microangiopathy. We present a case of atypical haemolytic uraemic syndrome likely triggered by chemo-immunotherapy which responded to eculizumab.
Case report: A 61-year-old female with triple-negative breast cancer (Grade 3, T2N1M0) was hospitalised with non-neutropenic fevers, diarrhoea, rash and malaise after completing 4 cycles of neoadjuvant pembrolizumab, carboplatin and paclitaxel and 1 of 4 planned cycles of neoadjuvant doxorubicin, cyclophosphamide and pembrolizumab. Her last dose of chemo-immunotherapy was 3 weeks prior to presentation. She had previously experienced uncomplicated febrile neutropenia but otherwise had no notable medical history. Day 3 of admission she developed oliguric acute kidney injury (creatinine increased from 54µmol/L to 417µmol/L) and thrombocytopaenia (platelet count fell from 227×109/L to 47×109/L) with microangiopathic haemolytic anaemia on blood film (LDH=2972U/L). ADAMTS13 level was 32%, direct antiglobulin testing and Shiga toxin were negative. On day 5 weekly eculizumab 900mg and prednisone (1mg/kg) treatment were commenced for a presumptive diagnosis of atypical haemolytic uraemic syndrome. Markers of haemolysis improved within 48-hours. Kidney biopsy performed on day 13 demonstrated acute thrombotic microangiopathy with glomerular infarction and mild acute interstitial nephritis. Intravenous methylprednisolone 1g for 3 days was added to therapy. She required 6 sessions of haemodialysis, but kidney function began to recover by day 20. On discharge (day 28) creatinine was 106µmol/L and by day 38 was 70µmol/L.
Conclusions: Thrombotic microangiopathies are a known side effect of traditional chemotherapy but are not currently well described in the literature secondary to ICI therapy. This case report highlights the need for rapid recognition of these side effects in order to institute early treatment and improve outcomes.