Pretargeted Anti-CD20 Radioimmunotherapy with scFv Fusion Protein Safely Combines with BEAM and ASCT in Patients with High-risk B-cell Lymphomas.

Despite new therapies, many patients with non-Hodgkin lymphoma (NHL) relapse and need more effective salvage therapies. This study (NCT02483000) evaluated the safety of B9E9-FP, a tetrameric single-chain anti-CD20-streptavidin fusion protein used in pretargeted radioimmunotherapy, when combined with BEAM and autologous stem cell transplantation (ASCT) for patients with NHL. Patients with high-risk NHL received B9E9-FP on day -17, clearing agent on day -15, and DOTA-biotin (DOTA-Bt) equally divided and labeled with dose-escalated yttrium-90 (90Y) or with indium-111 (for imaging) on day -14. BEAM chemotherapy started at day -7 before stem cell infusion. Three patients with NHL (mantle cell lymphoma, transformed diffuse large B-cell lymphoma, and de novo diffuse large B-cell lymphoma), ages 52 to 62 years, were treated with 30, 50, or 70 mCi (1,110, 1,850, or 2,590 MBq) 90Y/m2 before ASCT without any dose-limiting toxicity. One case of diarrhea (grade 2) and one case of rash (grade 1) were possibly associated with B9E9-FP or DOTA-Bt, respectively. Pharmacokinetic studies showed peak blood biological percent injected dose per gram blood (% ID/g) of 90Y-DOTA-Bt at 15 minutes after infusion (14.8%-49.4% ID), with only 0.82% to 2.59% ID after 72 hours. Uptake was preferential at bone marrow (1.73-5.96 cGy/mCi injected) and spleen (2.4-4.17 cGy/mCi injected) compared with lungs (0.19-0.48 cGy/mCi). Unbound 90Y-DOTA-Bt was excreted renally without any renal dysfunction noted up to 2 years later. Two of the three enrolled patients are alive and in remission 3.5 to 4.9 years after transplant. Pharmacokinetic, dosimetry, and outcome data support that B9E9-FP pretargeted radioimmunotherapy combined with 90Y-augmented ASCT DOTA-Bt is feasible.