Tumor Lysis Syndrome after Combination Therapy of Nivolumab and Sorafenib in a Woman with Advanced Hepatocellular Carcinoma

Abstract

Tumor lysis syndrome (TLS) is a life-threatening emergency that usually develops in rapidly proliferating hematologic malignancies or advanced solid tumor following cytotoxic chemotherapy or therapeutic interventions. TLS is especially rare in patients with hepatocellular carcinoma (HCC). Therefore, we present a case of a female patient with newly diagnosed advanced HCC who developed TLS and hepatic failure after receiving combination therapy of nivolumab and sorafenib. To our knowledge, this is the first case of TLS in a patient with advanced HCC owing to combination therapy of nivolumab and sorafenib. We also reviewed the literature and summarized the characteristics of TLS in patients with advanced HCC receiving various therapeutic interventions. The overall mortality rate was 63% and regarding the management, transarterial chemoembolization (TACE) was the most common etiology. TACE-related TLS developed more rapidly than sorafenib-related TLS. Furthermore, the efficacy and safety of combination therapy of nivolumab and sorafenib should be further evaluated, and TLS should still be a concern, especially in patients with large tumor burden.

Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study

“…However, some metabolic disorders in the context of TLS including hyperkalemia and acute kidney injury were occasionally reported in association with pembrolizumab ( Langer et al, 2016 ; Goldberg et al, 2020 ; Middleton et al, 2020 ), avelumab ( Barlesi et al, 2018 ), and durvalumab uses ( Massard et al, 2016 ). Currently, just eight case reports of individuals developing TLS while receiving treatment with ICIs or co-chemotherapy have been reported in the PubMed database ( Masson Regnault et al, 2017 ; Fa’ak et al, 2019 ; Carrier et al, 2020 ; Magara et al, 2020 ; Narukawa et al, 2020 ; Shah et al, 2020 ; Sugimoto et al, 2020 ; Yen et al, 2020 ). All cases involved solid tumors—three cases of metastatic melanoma ( Masson Regnault et al, 2017 ; Magara et al, 2020 ; Sugimoto et al, 2020 ), three cases of genitourinary malignancies ( Fa’ak et al, 2019 ; Narukawa et al, 2020 ; Shah et al, 2020 ), one case of hepatocellular carcinoma ( Yen et al, 2020 ), and one case of metastatic triple-negative breast cancer ( Carrier et al, 2020 ).…”

“…Currently, just eight case reports of individuals developing TLS while receiving treatment with ICIs or co-chemotherapy have been reported in the PubMed database ( Masson Regnault et al, 2017 ; Fa’ak et al, 2019 ; Carrier et al, 2020 ; Magara et al, 2020 ; Narukawa et al, 2020 ; Shah et al, 2020 ; Sugimoto et al, 2020 ; Yen et al, 2020 ). All cases involved solid tumors—three cases of metastatic melanoma ( Masson Regnault et al, 2017 ; Magara et al, 2020 ; Sugimoto et al, 2020 ), three cases of genitourinary malignancies ( Fa’ak et al, 2019 ; Narukawa et al, 2020 ; Shah et al, 2020 ), one case of hepatocellular carcinoma ( Yen et al, 2020 ), and one case of metastatic triple-negative breast cancer ( Carrier et al, 2020 ). These patients were treated with atezolizumab, nivolumab, or ipilimumab monotherapy ( Masson Regnault et al, 2017 ; Fa’ak et al, 2019 ; Sugimoto et al, 2020 ); combined therapy of nivolumab plus ipilimumab ( Magara et al, 2020 ); co-chemotherapy with nanoparticle albumin-bound-paclitaxel and atezolizumab ( Carrier et al, 2020 ); nivolumab plus sorafenib ( Yen et al, 2020 ); pazopanib after nivolumab ( Narukawa et al, 2020 ); or pembrolizumab plus axitinib ( Shah et al, 2020 ).…”

“…TLS onset was between 5 and 10 days after the initiation of therapy, with various clinical symptoms such as weakness, fatigue, nausea, vomiting, diarrhea, and abdominal pain. Five out of eight patients died within 3–22 days after hospital admission ( Masson Regnault et al, 2017 ; Narukawa et al, 2020 ; Shah et al, 2020 ; Sugimoto et al, 2020 ; Yen et al, 2020 ) and one after being discharged for home hospice ( Fa’ak et al, 2019 ).…”

“…Currently, just eight case reports of individuals developing TLS while receiving treatment with ICIs or co-chemotherapy have been reported in the PubMed database (Masson Regnault et al, 2017;Fa'ak et al, 2019;Carrier et al, 2020;Magara et al, 2020;Narukawa et al, 2020;Shah et al, 2020;Sugimoto et al, 2020;Yen et al, 2020). All cases involved solid tumors-three cases of metastatic melanoma (Masson Regnault et al, 2017;Magara et al, 2020;Sugimoto et al, 2020), three cases of genitourinary malignancies (Fa'ak et al, 2019;Narukawa et al, 2020;Shah et al, 2020), one case of hepatocellular carcinoma (Yen et al, 2020), and one case of metastatic triple-negative breast cancer (Carrier et al, 2020). CTLA-4, cytotoxic T lymphocyte antigen-4; PD-1, programmed death receptor-1; PD-L1, programmed cell death 1 ligand 1; N, number of cases; ROR, reporting odds ratio; CI, confidence interval; PRR, proportional reporting ratio; χ2, chi-squared; IC, information component; IC025, the lower limit of the 95% two-sided CI of the IC; EBGM, empirical Bayesian geometric mean; EB05, the lower 90% one-sided CI of EBGM.…”

“…These patients were treated with atezolizumab, nivolumab, or ipilimumab monotherapy (Masson Regnault et al, 2017;Fa'ak et al, 2019;Sugimoto et al, 2020); combined therapy of nivolumab plus ipilimumab (Magara et al, 2020); cochemotherapy with nanoparticle albumin-bound-paclitaxel and atezolizumab (Carrier et al, 2020); nivolumab plus sorafenib (Yen et al, 2020); pazopanib after nivolumab (Narukawa et al, 2020); or pembrolizumab plus axitinib (Shah et al, 2020). The age range of the patients was 37-79 years, with a mean age of 58.5 years.…”