On September 24, 2018, the US FDA granted regular approval to duvelisib (Copiktra®, Verastem) for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) after ≥2 prior therapies.

IPI-145-07 Study

The multicenter, open-label IPI-145-07 study (NCT02004522) randomised 196 patients with R/R CLL or SLL 1:1 to receive either duvelisib 25 mg orally (PO) twice daily (BID or intravenous (IV) ofatumumab at an initial dose of 300 mg, weekly 2000 mg IV for 7 doses, followed by 2000 mg IV once every 4 weeks for 4 additional infusions.

The estimated median progression-free survival (PFS) by independent review committee (IRC), was 16.4 months for patients treated with duvelisib and 9.1 months for patients receiving ofatumumab (HR=0.40; SE 0.2). The overall response rate (ORR) by IRC measured 78% in the duvelisib arm and 39% in the ofatumumab arms (SE 6.5%).

Safety and Boxed Warnings

The FDA approved prescribing information contains boxed warnings for fatal/serious infection, diarrhoea or colitis, cutaneous reactions, and pneumonitis. The approved label includes warnings for neutropenia and hepatotoxicity.

Of the 442 patients with hematologic malignancies who received duvelisib at the approved dosing, 65% experienced serious adverse reactions (ARs), most commonly infection, diarrhoea or colitis, and pneumonia. Common ARs in ≥20% of patients include diarrhoea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection (URI), pneumonia, musculoskeletal pain, and anaemia. Permanent discontinuation of duvelisib due to ARs occurred in 35% of patients, and 24% of patients treated with duvelisib had a dose reduction.

Prescribing information Copiktra