PB2110: 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

Abstract

Background: The combination of tafasitamab + lenalidomide (LEN) has been granted accelerated approval in the United States (2020) and is conditionally approved in Canada and Europe (2021) for R/R DLBCL in autologous stem-cell transplant-ineligible adult patients. A tolerable safety profile for rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) + tafasitamab ± LEN in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) in the Phase Ib First-MIND study (NCT04134936) was previously reported, with clinically meaningful efficacy for R-CHOP + tafasitamab + LEN compared to R-CHOP + LEN (ASH 2021; #3556). Aims: To report pharmacokinetics, pharmacodynamics, and immunogenicity in patients with newly diagnosed DLBCL after adding tafasitamab ± LEN to R-CHOP as first-line treatment. Methods: Eligible patients were ≥18 years with treatment-naïve DLBCL, International Prognostic Index 2–5, and Eastern Cooperative Oncology Group performance score 0–2. Patients were randomized 1:1 to either six 21-day (D) cycles (C) of R-CHOP (R-CHO, D1; P, D1–5) + tafasitamab (12 mg/kg IV, D1, 8, 15) (Arm A) or R-CHOP + tafasitamab + LEN (25 mg orally, D1–10) (Arm B). Secondary endpoints included tafasitamab serum concentration and number and percentage of patients developing anti-tafasitamab antibodies. Exploratory endpoints included natural killer (NK) cell, T-cell, and B-cell count in peripheral blood. Results: In total, 83 patients were screened; 66 were randomized (Arm A, n=33; Arm B, n=33). The data cut-off was 13 March 2021 for the safety analysis, including ≥1 month follow-up after end of treatment (EoT) visit for all patients, and 15 September 2021 for the efficacy analysis. 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. This patient showed pre-existing anti-tafasitamab antibodies at baseline, which decreased during treatment. Median NK cell counts decreased from baseline at C1 D8, but were at baseline or higher levels by EoT visit (Arm A) and C1 D15 (Arm B; Table). T-cell counts decreased from baseline at C1 D8 in both arms but were at baseline level or higher by C1 D15 (Arm A) and EoT visit (Arm B). Median B-cell counts decreased from baseline to 0 cells/μL (Arm A, C1 D15; Arm B, C1D8); at 6-month follow-up after EoT visit, B-cell counts had recovered to measurable levels in ~50% of patients. Image:Summary/Conclusion: Tafasitamab serum concentration reached and maintained a therapeutic dose level in this first-line regimen and declined in line with known tafasitamab half-life (~16 days) after treatment completion; tafasitamab levels were comparable between the two treatment arms. No patients developed treatment-induced or treatment-boosted anti-tafasitamab antibodies. Median NK, T-cell, and B-cell counts were comparable between treatment arms in all cycles. NK and T-cell counts recovered to baseline levels by EoT; further follow up on B-cell recovery will be performed.