Assessing the Predictive Value of Plasma FLT3-L Levels for Hematologic Toxicity after Yttrium-90 Ibritumomab Tiuxetan ([⁹⁰Y]-Zevalin) Given as Consolidation in Patients with Advanced B-Cell Follicular NHL Responding to First Line Therapy.

Background: [⁹⁰Y]-Zevalin is a radiolabeled monoclonal antibody approved for the treatment of relapsed or refractory low-grade follicular or transformed B-cell NHL. Myelosuppression following [⁹⁰Y]-Zevalin is reversible with nadir counts at 7 to 9 wks after administration of Zevalin and grade 4 thrombocytopenia, neutropenia, and anemia occurring in 10%, 30%, and 3% of patients (pts), respectively. Currently, baseline platelet counts and the degree of bone marrow involvement are the most reliable predictors of hematologic toxicity. Recently, plasma FLT3-L levels have been shown to reflect more accurately bone marrow radiosensitivity to iodine I-131 radioimmunotherapy than peripheral blood counts in patients with solid tumors. The purpose of this analysis was to determine if plasma FLT3-L cytokine levels would help to predict the magnitude of hematologic toxicity after [⁹⁰Y]-Zevalin treatment.

Methods/Results: In this prospective, multicenter, phase III clinical trial, [⁹⁰Y]-Zevalin was studied as consolidation therapy (14.8 MBq/kg [0.4 mCi/kg; maximum 32 mCi]) versus no further treatment in 414 patients with advanced follicular-NHL responding to first-line induction therapy with single-agent chlorambucil, CVP, CHOP/CHOP-like regimens, or regimens containing fludarabine or rituximab. Pts were required to have an absolute neutrophil count (ANC) of at least 1500/μL and a platelet count of >150,000/μL. Hematologic toxicity was determined by collecting hematologic data (platelets, ANC, and hemoglobin [Hb]) before therapy and weekly thereafter for 14 wks. Plasma FLT3-L cytokine levels were evaluated in 71 of 208 patients before treatment with [⁹⁰Y]-Zevalin. FLT3-L levels (pg/mL) were determined by immunoassay with a reference range from 48.3 to 173.8pg/mL. The mean FLT3-L level of all pts was 140.8 (range 49.5 to 300.4). The incidences of grade 3/4 thrombocytopenia, neutropenia, and anemia were 46.5%/8.5%, 40.8%/33.8%, and 8.5%/4.2%, respectively. Severe hematologic events were transient. The FLT3-L levels were not correlated with the nadir of platelets, ANC and Hb per patient during week 1 to 14. The correlation coefficent between FLT3-L and platelets, ANC and Hb was 0.10, −0.25 and −0.18, respectively for all pts. These results do not indicate a relationship between baseline FLT3-L and any of the 3 hematologic parameters.

Conclusions: Baseline FLT3-L levels did not identify pts who are likely to develop a grade 3/4 myelosuppression following [⁹⁰Y]-Zevalin consolidation therapy. Overall, the incidence and severity of cytopenias were transient, reversible, and comparable to those obtained with [⁹⁰Y]-Zevalin in relapsed/refractory follicular NHL.