Belantamab mafodotin concentration-QTc relationships in patients with relapsed or refractory multiple myeloma from the DREAMM-1 and -2 studies.
Br J Clin Pharmacol
; 90(10): 2571-2581, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-38924122
ABSTRACT
AIMS:
To evaluate relationships between plasma concentrations of belantamab mafodotin, total monoclonal antibody, and its payload and changes in electrocardiogram (ECG) parameters in patients with relapsed or refractory multiple myeloma from the DREAMM-1 and DREAMM-2 studies.METHODS:
Hysteresis plots and linear regression analyses of pharmacokinetic (PK) analyte (belantamab mafodotin, total monoclonal antibody, and cytotoxic cysteine-maleimidocaproyl monomethyl auristatin F payload) concentrations vs. time-matched ECG parameters (absolute/change from baseline in QT interval corrected for RR interval [QTc/ΔQTc] and QT interval corrected for heart rate by Fridericia's formula [QTcF/ΔQTcF]) were performed. Concentrations of PK analyte required for a 10-ms increase in QTc in DREAMM-2 were calculated via simulation, as was the probability of ΔQTc/ΔQTcF exceeding 10 ms for the expected Cmax of PK analyte concentrations associated with the doses (2.5 and 3.4 mg/kg) administered in DREAMM-2.RESULTS:
Time-matched PK and ECG data from 290 patients (DREAMM-1, n = 73; DREAMM-2, n = 217) were analysed. Hysteresis plots did not clearly indicate any concentration-related prolongation in QTc or QTcF; regression analyses indicated a very small rate of increase in ΔQTc and ΔQTcF with increasing concentrations of PK analytes. Calculated concentrations of PK analyte required for a 10-ms prolongation in QTc were higher than the maximum analyte concentrations observed following treatment with belantamab mafodotin in DREAMM-2; the probability that each dose would prolong ΔQTc and ΔQTcF by >10 ms was 0 and <0.25%, respectively.CONCLUSION:
This study of belantamab mafodotin and its payload did not provide evidence of QT prolongation in patients with relapsed or refractory multiple myeloma at clinically relevant doses.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Electrocardiografía
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Anticuerpos Monoclonales Humanizados
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Mieloma Múltiple
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido