ABCL-022 Pharmacokinetics and Pharmacodynamics in First-MIND: A Phase Ib, Open-Label, Randomized Study of Tafasitamab ± Lenalidomide + R-CHOP in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

Context: The chemo-free immunotherapy tafasitamab + lenalidomide was granted accelerated approval in the United States (2020) and conditional approval in Canada and Europe (2021) for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in autologous stem cell transplant–ineligible adult patients. We report pharmacokinetics, pharmacodynamics, and immunogenicity in patients with newly diagnosed DLBCL after adding tafasitamab ± lenalidomide to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment. Objective: To study the pharmacokinetics, pharmacodynamics, and immunogenicity of tafasitamab. Design: Open-label, randomized, multicenter. Setting: Fifty sites in North America and Europe. Patients: Eligible patients were ≥18 years with treatment-naïve DLBCL, IPI 2–5, and ECOG PS 0–2. Interventions: Patients were randomized 1:1 to six 21-day (D) cycles (C) of either R-CHOP (R-CHO, D1; P, D1–5) + tafasitamab (12 mg/kg IV, D1, 8, 15) (Arm A) or R-CHOP + tafasitamab + lenalidomide (25 mg orally, D1–10) (Arm B). Outcome Measures: Tafasitamab serum concentration and the number and percentage of patients developing anti-tafasitamab antibodies were secondary endpoints. NK-cell, T-cell, and B-cell counts in peripheral blood were exploratory endpoints. Results: Tafasitamab serum concentrations reached steady state by C3 (geometric mean trough concentrations: Arm A, 186.40–216.55 µg/mL; Arm B, 171.77–201.54 µg/mL) and steadily declined after treatment completion. Anti-tafasitamab antibodies were detected in 1/65 (1.5%) patients and decreased during treatment. Median NK-cell counts decreased from baseline at C1D8 but were at baseline or higher levels by end-of-treatment (EoT) visit (Arm A) and C1D15 (Arm B). T-cell counts decreased from baseline at C1D8 in both arms but were at baseline or higher by C1D15 (Arm A) and EoT visit (Arm B). Median B-cell counts decreased from baseline to 0 cells/µL (Arm A, C1D15; Arm B, C1D8); at 6-month follow-up after EoT visit, B-cell counts recovered to measurable levels in ~50% of patients. Conclusions: Tafasitamab serum concentration reached and maintained a therapeutic dose level and declined after treatment completion. No patients developed treatment-induced or treatment-boosted anti-tafasitamab antibodies. Median cell counts for NK cells, T cells, and B cells were comparable between treatment arms in all cycles. Funding: MorphoSys AG.