30 August 2023: Articles
Bevacizumab-Associated Thrombotic Microangiopathy Treated with Eculizumab: A Case Report
Challenging differential diagnosis, Unusual setting of medical care, Rare disease, Adverse events of drug therapy, Educational Purpose (only if useful for a systematic review or synthesis)
Wallace Stwart Carvalho Padilha A* , Bruno Nogueira Cesar A , Samara Theodoro Pacheco B , Alessandra Alves De Sousa B , Felipe Lourenço Ledesma C , Denise Maria Avancini Costa Malheiros C , Marcela Crosara Alves Teixeira ADOI: 10.12659/AJCR.940906
Am J Case Rep 2023; 24:e940906
Table 2. Summary of case reports of bevacizumab-induced TMA treated with eculizumab.
| Reference | Age/sex | Cancer | Exposure | Kidney parameters | Eculizumab treatment | Outcome |
|---|---|---|---|---|---|---|
| []5 | 73 F | Stage IV intrahepatic cholangiocarcinoma | Gemcitabine, capecitabine, bevacizumab(24 cycles) | AKI with dialysis requirement; kidney biopsy with TMA | 900 mg weekly ×4, 1200 mg every week ×2 (total 6 doses) | SCr stabilized higher than baseline and off dialysis; opted for supportive care; POD and died 4 months later |
| []6 | 42 F | Stage III ovarian cancer | Liposomal doxorubicin, bevacizumab | Not described; no kidney biopsy description | Dose not described; 16 weeks | Improvement within 4 weeks of eculizumab, creatinine normalized by week 7; no TMA recurrence; POD and died 9 months later |
| []7 | 72 F | Stage IIB serous ovarian carcinoma, HTN | Carboplatin, paclitaxel (6 cycles with POD); bevacizumab (15 mg/Kg q4 wk), liposomal doxorubicin (40 mg/m q4 wk) (3 cycles) | HTN uncontrolled; AKI (sCr 1.77 from 0.9); no kidney biopsy description | 900 mg weekly ×4, 1200 mg week 5 then every 2 weeks | Hematologic improvement with 2 doses; kidney function stabilized; oncologic status not described |
| 62 F | Stage IIIC serous tubo-ovarian cancer, HTN, Multiple sclerosis | Carboplatin, paclitaxel (6 cycles); doxorubicin (40 mg/m q4 wk), bevacizumab (15 mg/Kg q4 wk) (9 cycles); POD, doxorubicin changed to cyclophosphamide, bevacizumab | AKI (sCr 4.08 from 2.05 at time of last bevacizumab dose); no kidney biopsy description | 900 mg weekly ×4, 1200 mg week 5 then every 2 weeks; Total 8 doses | Hemoglobin 7.5 g/dL, platelets 125k, sCr improved to 2.59; hospice due to cancer | |
| 74 F | Stage IV serous ovarian carcinoma, HTN, recurrent DVT | Carboplatin, paclitaxel (6 cycles); bevacizumab (15 mg/Kg q4 wk), liposomal doxorubicin (40 mg/m q4 wk) (8 cycles) | AKI (sCr 1.3 from 0.8); no kidney biopsy description | 900 mg weekly ×4, 1200 mg week 5 then every 2 weeks | Hematologic and kidney improvement within 4 weeks; resumed bevacizumab 5 mg/kg q4 wk with on-going eculizumab and oncologic clinical control after at least 6 months | |
| []8 | 69 F | Relapsed stage IV breast cancer | Paclitaxel, bevacizumab (49 cycles); mitomycin-C (total dose 30 mg/m); capecitabin | AKI with dialysis requirement; no kidney biopsy description | 900 mg weekly ×4, 1200 mg week 5 then every 2 weeks | Hematologic improvement; off dialysis; stopped eculizumab at 6 months for knee pain, TMA recurred, resumed eculizumab with improvement; then POD, remains on eculizumab and palliative care |
| []9 | 55 F | Stage IV colorectal adenocarcinoma | FOLFOX6 (oxaliplatin, leucovorin, fluorouracil), bevacizumab (stopped after 1 cycle due to thrombosis) | 9 months after Bevacizumab stopped: AKI (sCr 1.98), proteinuria of 11133 mg/24 h; no kidney biopsy description | 900 mg weekly ×4, 1200 mg every 2 weeks | After 2 weeks steroids and PEX renal function normalized but no hematological improvement, so eculizumab: hematological improvement after 2 weeks, stopped after 5 cycles due to pneumonia; then POD, started FOLFIRI (leucovorin, fluorouracil, irinotecan) without hematologic toxicity |
| []3 | 68 F | Stage IV ovarian high-grade serous carcinoma | PLD (30 mg/m q4 wk), bevacizumab (10 mg/Kg q2 wk) | After 4 bevacizumab dose and 2 months holding: HTN, AKI (sCr 3.7 from 0.9), proteinuria (UPCR 3.1); kidney biopsy with TMA | 900 mg weekly ×4 | sCr stabilized, UPCR 0.21; hematological improvement; cancer therapy was transitioned to paclitaxel; still alive 2 years after |
| 52 F | Stage IIIC poorly differentiated serous carcinoma, HTN | PLD (30 mg/m q4 wk), atezolizumab (800 mg q2 wk), bevacizumab (10 mg/Kg q2 wk) | Uncontrolled HTN; AKI (sCr 2.26 from 0.7); proteinuria (UPCR 1.69); kidney biopsy with TMA | 900 mg weekly ×4 (but stopped after 2 dose because of a rash) | sCr stabilized, UPCR 0.4; hematological improvement; eculizumab stopped due to rash; POD and died after | |
| []4 | 17 M | Desmoplastic small round cell tumor | Vincristine, irinotecan, temozolomide and bevacizumab (15mg/Kg q3 wk) | Decreased urine output; petechias; sCr 1.5, UPCR 2.5; kidney biopsy with TMA | 900 mg weekly ×4, 1200 mg every 2 weeks (5 doses total for 3 months) | No reduction in creatinine, nephrotic level proteinuria persisted; POD led to discontinuation of eculizumab; palliative chemo and hemodialysis, died 6 months after renal dysfunction |
| Current case | 64 F | Stage IV lobular breast cancer (hormonal receptor positive, Her2 negative), HTN | Fulvestrant (POD), followed by palbociclib and letrozole (POD, visceral crisis), followed by paclitaxel and bevacizumab) (10mg/Kg q3 wk) | HTN uncontrolled; AKI with dialysis requirement; proteinuria 1242 mg/24h; MAHA; kidney biopsy with TMA | 900 mg weekly ×4 | Hematologic improvement; off dialysis, with sCr stable at 1.36 mg/dL; HTN requiring 4 drugs; then POD, started exemestane and everolimus |
| F – female; M – male; HTN – hypertension; DVP – deep vein thrombosis; POD – progression of disease; wk – week; AKI – acute kidney injury; sCr – serum creatinine; UPCR – urine protein creatinine ratio (g/g); PEX – plasma exchange; MAHA – microangiopathic hemolytic anemia. | ||||||