SynthesisCPT: pharmacometrics & systems pharmacology2021
PK/PD modeling analysis for dosing regimen selection of isatuximab as single agent and in combination therapy in patients with multiple myeloma.
Synthesis in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- PK/PD modeling analysis for dosing regimen selection of isatuximab as single agent and in combination therapy in patients with multiple myeloma.CPT: pharmacometrics & systems pharmacology · 2021Pooled it
- Isatuximab in combination with cemiplimab in patients with relapsed/refractory multiple myeloma: A phase 1/2 study.Cancer medicine · 2023Trial
- Simulation Framework to Investigate Efficacy and Ocular Safety of Belantamab Mafodotin Combinations in Relapsed/Refractory Multiple Myeloma.CPT: pharmacometrics & systems pharmacology · 2026Article
- Comparative Molecular Insights and Computational Modeling of Multiple Myeloma and Osteosarcoma.International journal of molecular sciences · 2026Review
- Article
- Isatuximab-dexamethasone-pomalidomide combination effects on serum M protein and PFS in myeloma: Development of a joint model using phase I/II data.CPT: pharmacometrics & systems pharmacology · 2024Article
- Impact of Continuous Infusion Meropenem PK/PD Target Attainment on C-Reactive Protein Dynamics in Critically Ill Patients With Documented Gram-Negative Hospital-Acquired or Ventilator-Associated Pneumonia.Clinical pharmacokinetics · 2024Article
- Model-based simulation to support the approval of isatuximab alone or with dexamethasone for the treatment of relapsed/refractory multiple myeloma in Japanese patients.CPT: pharmacometrics & systems pharmacology · 2023Article
- Optimizing tylosin dosage for co-infection ofFrontiers in pharmacology · 2023Article
- Exposure-response analyses for selection/confirmation of optimal isatuximab dosing regimen in combination with pomalidomide/dexamethasone treatment in patients with multiple myeloma.CPT: pharmacometrics & systems pharmacology · 2022Article
- Joint modelling and simulation of M-protein dynamics and progression-free survival for alternative isatuximab dosing with pomalidomide/dexamethasone.British journal of clinical pharmacology · 2022Article
- Isatuximab in the Treatment of Multiple Myeloma: A Review and Comparison With Daratumumab.Technology in cancer research & treatmentReview
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This analysis describes the pharmacokinetic/pharmacodynamic (PK/PD) modeling framework that supported selection of the isatuximab (anti-CD38 monoclonal antibody) dosing regimen alongside its early clinical development in patients with relapsed/refractory multiple myeloma (RRMM). The PK/PD mathematical model characterized the variations of patient serum M-protein concentrations, the primary marker of tumor burden in multiple myeloma (MM). Three separate PK/PD models were built sequentially as data became available from phase I clinical trials. The primary PK/PD analysis was initiated using monotherapy phase I study data (n = 122), followed by analysis of data collected from phase Ib combination studies with lenalidomide and dexamethasone (Rd, n = 40) and then with pomalidomide and dexamethasone (Pd, n = 31). Using the PK/PD model, abnormal "myeloma" protein (M-protein) profiles under different isatuximab dosing regimens were simulated. Overall, simulations revealed that regimens which included a loading period of four weekly administrations followed by administration every 2 weeks thereafter (QW4-Q2W), reduced M-protein levels more than a Q2W regimen without a loading period. For isatuximab monotherapy, a 20 mg/kg dose induced greater reduction in serum M-protein levels compared with doses equal or lower than 10 mg/kg. For isatuximab in combination with either Rd or Pd, simulations yielded no substantial benefit in terms of M-protein reduction between isatuximab 10 mg/kg and 20 mg/kg. These PK/PD analyses supported the use of isatuximab 10 mg/kg QW4-Q2W in combination with Pd in the phase III trial.
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