A Pilot Study of Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan (Zevalin^®) in Patients with Relapsed and Refractory Classical Hodgkin Lymphoma (HL): Delivering Cross Fire Radiation by Targeting Reactive B Cells in the Microenvironment.

Both non-Hodgkin lymphoma (NHL) and HL are radiosensitive tumors. Although the efficacy of radioimmunotherapy (RIT) targeting CD20 antigen has been established in several types of B-cell NHL, no data exisit on the potential use of this approach in classical HL. The malignant Hodgkin and Reed-Sternberg (HRS) cells of HL infrequently express CD20 suggesting that classical HL may not be the optimal tumor to be targeted by this approach. However, HRS cells are frequently surrounded by reactive B lymphocytes that express CD20. Therefore, we hypothesized that targeting reactive B cells in HL microenvironment by RIT could deliver effective radiation dose to HL lymph nodes killing HRS cells by cross-fire effect. To test this hypothesis, we treated 4 patients with relapsed classical HL with Zevalin RIT. During the imaging phase, patients received a slow intravenous infusion of rituximab (250 mg/m2) followed by an intravenous injection of 4–5 mCi of In-111 labeled anti-CD 20 (In-111 Zevalin). Whole-body scans were performed at 2–4 hours and 40–48 hours after injection using a Siemens dual-head gamma camera. Simultaneous anterior and posterior projections were obtained at these time points. After ruling out any unfavorable biodistribution of Zevalin was confirmed on images at both time points, patients underwent the treatment phase which consisted of rituximab (250 mg/m2) followed by Y-90 anti-CD 20 (Y-90 Zevalin). To-date 4 patients are enrolled on study (ages 25, 31, 65, and 74 years). Two patients received prior ASCT, and 2 were treated after failing ABVD chemotherapy alone. All patients received 0.4 mCi/Kg up to a maximum dose of 32 mCi. Normal biodistribution of Zevalin was confirmed in all 4 patients during the imaging phase. No Zevalin-avid lesions was noted in one patient. There was faint visualization of some of the known lesions (by Ga-67 SPECT, CT or F-18 FDG PET) in the axilla and abdomen in 2 of the 4 patients. Intense Zevalin-uptake sites were identified in the supraclavicular, infraclavicular, mediastinal, hepatic and abdominal lymphatic chains in another patient. Imaging results and treatment responses are shown in the following table:

Treatment was well tolerated with hematologic toxicity similar to those observed in NHL patients. Our preliminary results suggest that RIT targeting reactive B cells in classical HL is feasible and safe. Future studies should incorporate pretreatment evaluation of a selected lymph node by fine needle aspiration to determine the fraction of reactive B cells in the microenvironment prior to treatment with RIT targeting CD20.