Related Experiment Video
Updated: Feb 1, 2026
Detection of Invasive Pulmonary Aspergillosis in Haematological Malignancy Patients by using Lateral-flow Technology
Published on: March 22, 2012
Effect of inotuzumab ozogamicin on the QT interval in patients with haematologic malignancies using QTc-concentration
Jennifer E Hibma1, Hagop M Kantarjian2, Daniel J DeAngelo3
1Pfizer Oncology, San Diego, CA, USA.
Aim:
The aim of this study was to characterize the effect of inotuzumab ozogamicin on QT interval in patients with B-cell malignancies.
Methods:
Data were pooled from three clinical studies including 250 patients (n = 2743) who received inotuzumab ozogamicin monotherapy. Patients with relapsed/refractory acute lymphoblastic leukaemia (NCT01564784 and NCT01363297) received 1.8 mg m-2 per cycle in divided doses (mean Cmax 371 ng ml-1 ; considered therapeutic) and patients with relapsed/refractory non-Hodgkin lymphoma (NCT00868608) received 1.8 mg m-2 per cycle as a single dose (mean Cmax 569 ng ml-1 ; considered supratherapeutic). Triplicate 12-lead electrocardiograms were performed at baseline and predefined time points postdose with paired pharmacokinetic collections. The exposure-response relationship between corrected QT interval (QTc: QT interval corrected using population-specific formula [QTcS] or QT interval corrected using Fridericia's formula [QTcF]) and inotuzumab ozogamicin concentration was characterized using a linear mixed-effects model, and simulations were performed using the final validated model. Full model development involved testing for covariates that may account for part of the identified variability.
Results:
QTc intervals had a small but positive correlation with inotuzumab ozogamicin concentration. Based on 1000 simulations, median (upper 95% CI) QTcS and QTcF changes from baseline were <10 ms at both therapeutic (2.70 ms [5.40 ms] and 2.53 ms [4.92 ms], respectively) and supratherapeutic (4.14 ms [8.28 ms] and 3.87 ms [7.54 ms], respectively) concentrations.
Conclusions:
Inotuzumab ozogamicin (1.8 mg m-2 per cycle) is not predicted to pose a clinically significant safety risk for QT prolongation in patients with acute lymphoblastic leukaemia or non-Hodgkin lymphoma.
Related Concept Videos
01:03Prediction Intervals
However, the point estimate is most likely not the exact value of the population parameter, but close to it. After calculating point estimates, we construct interval estimates, called confidence intervals or prediction intervals. This prediction interval comprises a range of values unlike the point estimate and is a better predictor of the observed sample value, y.
01:21Confidence Intervals
A...
01:29Improper Integrals: Infinite Intervals
02:41Concentration Cells
Consider the following voltaic cell:
00:55Interval Level of Measurement
Data measured using the interval scale are similar to ordinal level data because they have a definite arrangement. However, in the interval level of measurement, the differences between data values are meaningful even though the data does not have a starting point.
Temperature is measured using the interval scale. It is measurable data, and the difference between...
01:19Interpretation of Confidence Intervals
Confidence intervals have confidence coefficients that are crucial for their interpretation. The most common confidence coefficients are 0.90, 0.95, and 0.99, which can be written as percentages–90%, 95%, and 99%, respectively.
Suppose a person calculates a confidence interval with a confidence coefficient of 0.95. In that case, they can...