ASH 2019: Optimal Dosing of Duvelisib in Resistant Peripheral T-Cell Lymphoma
Posted: Friday, December 13, 2019
The dual PI3K-delta, gamma inhibitor duvelisib is clinically active in patients with relapsed or refractory peripheral T-cell lymphoma at both 25-mg and 75-mg dosages. Higher initial exposure may be important in aggressive disease, noted Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer, New York, who presented the findings of this phase II PRIMO trial on behalf of his colleagues at the 2019 American Society for Hematology (ASH) Annual Meeting & Exposition (Abstract 1567).
This trial recruited 33 patients with relapsed or refractory peripheral T-cell lymphoma with no history of allogeneic stem cell transplantation. Patients were randomly assigned to receive either 25 mg of duvelisib twice daily with an option for dose escalation or 75 mg of duvelisib twice daily until disease progression or unacceptable toxicity.
Patients included in the study had a median of 1.5 years since the time of their original diagnosis and were treated with a median of two prior therapies. All of the patients in the 75-mg group and 13 of 20 patients in the 25-mg group were able to complete at least one cycle of therapy before data analysis. In addition, CD4 cell counts of less than 50 cells/mm3 were associated with early discontinuation of the drug.
At a median follow-up of 20 months, four of seven responders in the 25-mg group and six of seven responders in the 75-mg group were still in response. The overall response rate was 41% in the 25-mg group and 67% in the 75-mg group. Pharmacokinetic analysis revealed that an adequate dose of the drug can be more rapidly and reliably achieved at higher drug doses.
Common grade three or higher adverse events included neutropenia, thrombocytopenia, and sepsis. Serious adverse events included colitis, pyrexia, disease progression, sepsis, pneumonia, hyponatremia, dyspnea, pneumonitis, and respiratory failure. A total of 12% of patients discontinued duvelisib due to adverse events.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
