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 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 pre-targeted radioimmunotherapy (PRIT), when combined with BEAM and autologous stem cell transplantation (ASCT) for NHL patients. High-risk NHL patients 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 (111In for imaging) on day -14. BEAM chemotherapy started day -7 before stem cell infusion. Three NHL patients (MCL, transformed DLBCL, and de novo DLBCL), ages 52-62 years, were treated with 30, 50, or 70 mCi (1110, 1850, or 2590 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 (PK) studies showed peak blood biological percent injected dose per gram blood (% ID/g) of 90Y-DOTA-Bt at 15 min after infusion (14.8 - 49.4 % ID), with only 0.82 - 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 to 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 3 enrolled patients are alive and in remission 3.5 to 4.9 years after transplant. PK, dosimetry, and outcomes data support that B9E9-FP PRIT and 90Y-augmented ASCT DOTA-Bt is feasible.