The successful combination of grapefruit juice and venetoclax in an unfit acute myeloid leukemia patient with adverse risk: A case report

Abstract

Venetoclax combined with hypomethylating agents such as azacitidine and decitabine is the standard regime for the elderly patient with acute myeloid leukemia (AML) unfit for intensive induction therapy. However, many patients struggle with finances and forgo treatments due to the high costs of venetoclax. In this study, we performed the regime with azacitidine, low-dose venetoclax, and grapefruit juice on an unfit AML patient with TP53 mutation. The peak venetoclax concentration (Cmax) and side effects on the patient were also monitored. The patient achieved complete remission with the venetoclax Cmax within the effective concentration range (1,000–3,000 ng/ml) and maintained durable remission until recently. Febrile neutropenia, thrombocytopenia, and pneumonia appeared during the first cycle and were recovered by stimulating agents and antibiotic treatment. This improvement combination approach by drug-food interaction may enlighten other similarly patients with AML, especially those in low-middle income countries.

Pharmacokinetic Boosting of Kinase Inhibitors

“…Venetoclax was boosted with grapefruit juice in a patient with AML who could not afford the regular dose of 400 mg QD [49]. Treatment started with venetoclax 100 mg QD in combination with 200 mL grapefruit juice TID.…”

“…Boosting of expensive drugs has the potential to drastically reduce treatment costs. The high cost-saving potential of the pharmacokinetic boosting of kinase inhibitors is quantified or projected in some trials [39,[45][46][47]49]. For some boosted kinase inhibitors, the clinical evidence for pharmacokinetic boosting safety and efficacy is already substantial.…”

“…Drugs with an exposure-response or exposure-toxicity relationship are good candidates to incorporate TDM in the boosting regimen, especially for drugs where TDM is already proven to be of benefit [61,62]. Dose adjustments for boosting can be estimated based on the known pharmacokinetic outcomes associated with efficacy and toxicity [49]. TDM guidance can therefore help individualizing the appropriate dose and potentially reduce exposure variability.…”

Venetoclax: A New Partner in the Novel Treatment Era for Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…It is crucial to closely observe patients undergoing treatment with venetoclax in conjunction with antifungal medications, and make adjustments to the dosage as necessary to minimize the risk of DDIs [ 55 ]. The recommended dosages for the administration of venetoclax in combination with HMA or chemotherapy is 400 mg/day, and 600 mg/day when used with LDAC [ 56 ].…”