FDA Approves Drug for Several Blood Cancers

The Food and Drug Administration (FDA) approved duvelisib (COPIKTRA) to treat adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies, as well as adult patients with follicular lymphoma (FL) after at least two prior systemic therapies. 

COPIKTRA, manufactured by drugmaker Verastem, is the first oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma. 

https://twitter.com/drhatton/status/1044581896871661568

Approval for CLL/SLL patients is standard, while indication in FL is approved under accelerated approval based on overall response rate. 

Duvelisib was in a randomized, multicenter, open-label trial that compared it to ofatumumab in patients with relapsed or refractory CLL or SLL. Randomized patients (n = 196) who received at least two prior therapies received either duvelisib (n = 95) or ofatumumab (n = 101). Duvelisib was administered orally twice a day (25 mg). Ofatumumab was administered intravenously first at 300 mg, then at 2,000 mg once a week for seven weeks, and then at 2,000 mg once every four weeks for four doses. 

FDA approves duvelisib for treatment of relapsed/refractory chronic lymphocytic #leukemia or small lymphocytic #lymphoma, and grants duvelisib accelerated approval for treatment of r/r #follicular lymphoma #leusm #lymsm https://t.co/qs6UDHW1Tv

— FDA Oncology (@FDAOncology) September 24, 2018

Median progression-free survival was 16.4 months in the duvelisib cohort and 9.1 months in the ofatumumab group (hazard ratio, 0.40; standard error, 0.2). 

Duvelisib was tested in a single-arm multicenter study in 83 FL patients who were refractory to rituximab and to either chemotherapy or radioimmunotherapy. Overall response rate was 42% (n = 35) (95% CI: 31, 54); 41% of patients had partial responses and one had a complete response. Forty-three percent of responding patients (n = 15) maintained responses for a minimum of six months, and 17% (n = 6) for at least one year. A planned randomized trial may be necessary for the continued approval for the FL indication to validate duvelisib’s clinical benefit.

Today, the FDA approved duvelisib for treatment of both CLL and FL. Though it's great to expand our options, duvelisib carries many of the same risks of idelalisib and was approved based on comparison with ofatumumab. https://t.co/ncd6urUjkD

— Amber Koehler, PA-C (@hemepa_c) September 24, 2018

The most common side effects associated with duvelisib (incidence ≥ 20%) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia. The drug also comes with warnings for fatal and/or serious infections, and neutropenia and hepatotoxicity. Thirty-five percent of patients stopped using duvelisib completely due to negative side effects, and 24% reduced their dosage. 

Read about venetoclax monotherapy for relapsed/refractory CLL here.

Source: FDA