Abstract
Yttrium 90 (90Y) ibritumomab tiuxetan therapy is an emerging treatment option for B-cell non-Hodgkin’s lymphoma (NHL) upon relapse or refractory status. Ibritumomab tiuxetan has been shown to produce high rates of response in heavily pretreated patients with NHL. Due to the potential for altered biodistribution, the administration of ibritumomab tiuxetan has been restricted to patients having acceptable renal function (serum creatinine <2 mg/dL) at treatment initiation. This case study discusses the effects of renal insufficiency and hemodialysis on the pharmacokinetics, biodistribution, and safety profile of ibritumomab tiuxetan. A 64-year-old diabetic male presented with progressive disease after a 4-year history of low-grade follicular CD20+ NHL. The patient had chronic renal insufficiency associated with hypertension, diabetes, and multiple renal cysts. At the initial visit, the patient met all the criteria for receiving ibritumomab tiuxetan therapy except for impaired renal function, for which he was undergoing thrice-weekly hemodialysis. Ibritumomab tiuxetan therapy was administered in August 2002 according to the standard procedure, although the volume of rituximab was adjusted to prevent overloading the patient. Whole blood clearance of the imaging dose of indium 111 (111In) ibritumomab tiuxetan (53 h) was within the expected range for patients with normal renal function. Analyses of whole blood samples, obtained immediately before and after hemodialysis, indicated that there was not a significant clearance of 111In ibritumomab tiuxetan in the dialysate. Ibritumomab tiuxetan 32 mCi was administered on day 7. Platelet count (15,000 cells/mm3) and ANC (200 cells/mm3) nadir occurred at 8 and 10 weeks after therapy, with grade 3/4 cytopenia lasting 6 and 12 weeks, respectively. Both hematopoietic and growth factors were administered to support platelet and neutrophil recovery. Minimal safety precautions are required for ibritumomab tiuxetan administration, consequently shielding of hospital personnel or equipment was not needed during hemodialysis. Radioactive contamination of the dialysis equipment was not detected, and all components exposed to radiation were disposable. Additional measures beyond universal dialysis precautions were unnecessary. The patient had a partial response to 90Y ibritumomab tiuxetan therapy lasting approximately 6 months. One month following treatment he experienced improvements in renal pathologic adenopathy as detected by transaxial CT examination. However, some months later there was evidence of renal progression. In November 2003, the patient died of sepsis. This case illustrates that 90Y ibritumomab tiuxetan therapy is feasible and may achieve responses in patients with relapsed or refractory B-cell NHL who have concurrent chronic renal failure and are undergoing hemodialysis. Radiation safety concerns related to hemodialysis were minimal and easily managed. The biodistribution of 111In ibritumomab tiuxetan was relatively normal, thereby permitting administration of the therapeutic dose.
