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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

D. Belada, K. Kopeckova, JMB. Burgues, D. Stevens, GS. Nowakowski, M. Waldron-Lynch, N. Hadar, J. Weirather, C. Lässig, D. Blair, M. Dreyling

. 2022 ; 22 Suppl 2 (-) : S352. [pub] -

Jazyk angličtina Země Spojené státy americké

Typ dokumentu klinické zkoušky, fáze I, časopisecké články, multicentrická studie, randomizované kontrolované studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024252

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.

Citace poskytuje Crossref.org

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$a 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.
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