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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Toxicity patterns of novel PI3K combinations in patients with non-Hodgkin lymphoma
Thomas D Rodgers1, AnnaLynn M Williams1, Andrea Baran1
1James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Abstract:
Phosphoinositide-3-kinase (PI3K) inhibitors have efficacy in lymphoid malignancies; however, inflammatory and infectious toxicities can compromise the treatment course. An improved understanding of these toxicities will guide clinical use and further development. We evaluated the occurrence of treatment-related adverse events (AEs) in a retrospective review of 79 patients treated in standard fashion with PI3K inhibitor monotherapy or with anti-CD20 monoclonal antibodies or as part of a novel combination regimen. Patients treated with a novel combination were at a higher risk of developing a severe AE compared to those treated with standard therapy (HR 1.89, 95% CI 1.02, 3.49; p = .04). Additionally, previously untreated patients were at higher risk of developing a severe AE compared to previously treated patients (HR 3.19, 95% CI 1.48, 6.84; p = .003). These results caution against the use of untested PI3K inhibitor combinations in routine practice and suggest that early phase clinical trials should utilize conservative treatment schemas.
Insights
Novel combinations of phosphoinositide-3-kinase (PI3K) inhibitors increase severe adverse events in lymphoid malignancies. Previously untreated patients also face higher risks, suggesting cautious use in clinical trials.
Area of Science:
- Oncology
- Pharmacology
- Hematology
Background:
- Phosphoinositide-3-kinase (PI3K) inhibitors show promise in lymphoid malignancies.
- Treatment-related toxicities, including inflammatory and infectious adverse events (AEs), can impede patient treatment.
- Understanding these toxicities is crucial for optimizing clinical application and drug development.
Purpose of the Study:
- To evaluate the incidence of treatment-related AEs in patients receiving PI3K inhibitor therapy.
- To compare AE risk between standard and novel combination regimens.
- To identify patient factors associated with increased AE risk.
Main Methods:
- Retrospective review of 79 patients treated with PI3K inhibitor monotherapy, standard combinations, or novel regimens.
- Analysis of treatment-related adverse events (AEs).
- Statistical comparison of AE occurrence using hazard ratios (HR) and confidence intervals (CI).
Main Results:
- Patients on novel PI3K inhibitor combinations had a higher risk of severe AEs (HR 1.89, p=0.04).
- Previously untreated patients faced a significantly higher risk of severe AEs compared to previously treated patients (HR 3.19, p=0.003).
Conclusions:
- Novel PI3K inhibitor combinations are associated with increased severe adverse events.
- Untested PI3K inhibitor combinations should be used cautiously in clinical practice.
- Early-phase clinical trials should employ conservative treatment strategies for PI3K inhibitors.
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