Chemotherapy for non‐Hodgkin lymphoma in the hemodialysis patient: A comprehensive review

Abstract

Chemotherapy for non‐Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)‐like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and 90Y‐ibritumomab tiuxetan.

Chimeric antigen receptor T-cell therapy in a dialysis patient with lymphoma

“…14 Since HD typically removes 22%–37% of cyclophosphamide, it may be reasonable to proceed with a more moderate dose adjustment when administered pre-HD. 4 The risk of increased fludarabine toxicities can be mitigated with the use of reduced dosing and hemodialysis. 8,15 Kielstein et al examined the dialysate and fludarabine pharmacokinetics in a patient with acute anuric renal failure and demonstrated that the average dialysis clearance was only 25% of the clearance seen in patients without renal failure, thus highlighting the importance of also incorporating a reduced fludarabine dose.…”

“…The dose-limiting toxicity of fludarabine is myelosuppression and correlates with a higher area under the curve (AUC) levels and reduced renal clearance. 3,4 Specifically, the use of fludarabine as part of lymphodepleting chemotherapy poses a significant risk to ESKD patients, given that 27%–60% of its active metabolite is renally cleared. 3,5 In addition, patients with renal dysfunction demonstrate an increased risk of fludarabine-induced neurologic toxicity, which in turn may increase the risk of immune effector cell-associated neurotoxicity syndrome (ICANS), a specific form of neurotoxicity associated with CAR-T. 6 While the half-life of the active fludarabine metabolite is 20 h in vivo, delayed onset neurologic symptoms on the order of months have been reported.…”

Hodgkin Lymphoma on Hemodialysis Successfully Treated with Extended Courses of Brentuximab Vedotin

“…However, pharmacokinetic studies of BV in HD patients are lacking, and thus the optimal dose and timing of BV administration in HD patients is unknown. Under these circumstances, reports of actual BV administration and treatment outcomes are extremely valuable for decision making, but only one report of BV administration in an HD patient exists [ 6 ]. Nanni et al [ 7 ] reported successful treatment of an sALCL patient on HD with BV monotherapy every 3 weeks for 16 courses, and they reduced the dose of BV from the standard 1.8 mg/kg to 1.2 mg/kg according to the results reported by Zhao et al [ 5 ].…”

Tafasitamab and lenalidomide for relapsed/refractory diffuse large B-cell lymphoma in a patient on chronic intermittent hemodialysis

“…Also, DLBCL is most often treated with multiagent regimens, which can be more difficult to tolerate in patients with underlying comorbidities and organ dysfunction. 2…”

“…Also, DLBCL is most often treated with multiagent regimens, which can be more difficult to tolerate in patients with underlying comorbidities and organ dysfunction. 2 Tafasitamab is a humanized, Fc-modified anti-CD19 monoclonal antibody indicated for the treatment of R/R DLBCL in combination with lenalidomide for transplant-ineligible patients. 3 Patients with a creatinine clearance of <60 ml/min were excluded from the L-MIND trial, so experience with tafasitamab/lenalidomide is limited in patients with renal insufficiency.…”