FDA Warns About Possible Increased Risk of Death and Side Effects With Duvelisib
Duvelisib shows possibility of increased risk of death and serious side effects vs other medicines in patients with leukemia and lymphoma.
The FDA warns that treatment with duvelisib (Copiktra) may lead to increased risk of death vs other medicines in patients with leukemia and lymphoma, according to results from a clinical trial of duvelisib.
Duvelisib was also found to be associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood.
The FDA recommends that patients should talk to their health care providers about the risks vs benefits duvelisib while health care professionals should consider these risks and benefits compared to other treatments. They should also advise patients of the possible increased risk of death and higher risk of serious adverse events while taking this drug.
Previously, duvelisib was approved by the FDA in 2018 for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or relapsed/refractory follicular lymphoma. Both indications were patients who previously received at least 2 therapies.
The approval was based on findings from the phase 3 DUO trial (NCT02004522) and the phase 2 DYNAMO study (NCT01882803).
In DUO, duvelisib was shown to reduce the risk of disease progression or death by 60% vs 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 compared to 9.1 months with ofatumumab (HR, 0.40). In the DYNAMO study, duvelisib demonstrated an overall response rate (ORR) of 42% in patients with follicular lymphoma.
The phase III DUO study randomized 319 patients with CLL/SLL in a 1:1 ratio to duvelisib at 25 mg twice daily until disease progression or unacceptable toxicity, or ofatumumab at 300 mg on day 1, followed by 7 weekly infusions and 4 monthly infusions of 2000 mg.
The FDA based its approval on a subset of these patients with CLL/SLL who had received ≥2 prior lines of therapy. The subset included 95 patients randomized to duvelisib and 101 patients who received ofatumumab. This median patient age across this subset was 69 years (range, 40-90), 88% had an ECOG performance status of 0 or 1, and 59% were male. At baseline, 22% of patients had a detected 17p deletion and 52% had 1 or more tumors ≥5 cm. Over half (54%) of this group had received ≥3 prior treatment lines, with the remaining 46% having received 2.
The median duration of treatment exposure for the duvelisib arm was 13 months (range, 0.2-37). Patients were exposed to ofatumumab for a median duration of 5 months (range, <0.1 to 6). The ORR was 78% with duvelisib versus 39% with ofatumumab.
