FDA Approved Duvelisib for CLL and Follicular Lymphoma
Approved for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or relapsed/refractory follicular lymphoma.
It inhibits B cell receptor signaling, chemotaxis of malignant T cells, and T-cell migration.
An Oral inhibitor of PK3I kinase delta and gamma.
Delta isoform is expressed in malignant CLL cells, the gamma isoform is important in the microenvironment that supports the growth and proliferation of CLL cells.
By inhibiting both isoforms it has direct effect on malignant cells as well as the micro environment.
Metabolize predominately by the liver via CYP3A4 and is a moderate Inhibitor of CYP3A4.
Caution should be used with CYP3A4 strong inhibitors or inducers.
Both indications are for the treatment of patients who have received at least 2 prior therapies.
The approval is based on data from the phase III DUO trial and the phase II DYNAMO study.
In DUO, duvelisib reduced the risk of disease progression or death by 60% versus ofatumumab (Arzerra) in patients with relapsed/refractory CLL/SLL who had received at least 2 prior lines of therapy.
The median progression-free survival was 16.4 months with duvelisib versus 9.1 months with ofatumumab.
In the DYNAMO study, duvelisib demonstrated an overall response rate of 42% in patients with follicular lymphoma.
Duvelisib, an oral PI3K inhibitor targeting both the δ and γ catalytic subunits, approved for relapsed/refractory indolent BCL including FL after ≥2 prior lines of therapy based on results of the phase II DYNAMO trial.
Duvelisib ORR was 46% and median PFS and OS were 8.4 and 18.4 months, respectively, among patients refractory to both rituximab and alkylating chemotherapy.
Has potential risk of infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.
Side effects are common and include edema, fever, fatigue,headache, rash, colitis, diarrhea, nausea, abdominal pain, vomiting, mucositis, Pancytopenia, hyponatremia, hyperkalemia, hypocalcemia, hypokalemia, Elevated liver functions, factious predisposition, increased serum creatinine, and respiratory infections.
Increased risk of infections suggests pneumocystis pneumonia prophylaxis and acyclovir prophylaxis against herpes virus should bre considered.
Administered as a capsule swallowed whole, twice daily with or without food.
Available in 15 mg and 25 mg capsules.
The normal dose is 25 mg twice per day.