The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion recommending the approval of single-agent duvelisib for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia following at least 2 prior therapies, and follicular lymphoma that is refractory to at least 2 prior systemic treatments.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of single-agent duvelisib (Copiktra) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) following at least 2 prior therapies, and follicular lymphoma that is refractory to at least 2 prior systemic treatments.1
“Today’s positive opinion from the CHMP is an important step on the path toward authorization in Europe for [duvelisib] which is expected to improve overall response rates in patients suffering from relapsed and/or refractory CLL and follicular lymphoma, who currently have limited treatment options,” David Cohan, MD, chief medical officer of Secura Bio, stated in a press release. “Assuming approval, [duvelisib] will provide patients and physicians across much of Europe with a treatment option that works differently from other available therapies for these incurable diseases.”
In the phase 3 DUO trial (NCT02004522), duvelisib resulted in a 60% reduction in the risk of disease progression or death compared with ofatumumab in patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) who had previously received at least 2 lines of therapy.2 The median progression-free survival (PFS) with duvelisib in this population was 16.4 months vs 9.1 months with ofatumumab (HR, 0.40).2 Additionally, in the phase 3 DYNAMO trial (NCT01882803), duvelisib elicited an overall response rate (ORR) of 42% in patients with follicular lymphoma.
In DUO, a total of 319 patients with CLL/SLL were randomized 1:1 to receive either duvelisib at a twice-daily dose of 25 mg until progressive disease or intolerable toxicity, or a 300-mg dose of ofatumumab on day 1, followed by 7 weekly infusions and 4 monthly infusions of 2000 mg.
In a subset of patients with CLL/SLL who had previously received at least 2 lines of therapy, 95 received duvelisib and 101 were given ofatumumab. The median patient age across this subset was 69 years, 88% had an ECOG performance status of 0 or 1, and 59% were male. Twenty-two percent of patients had a detected 17p deletion at baseline, while 52% had 1 or more tumors that were 5 cm or larger. Fifty-four percent of patients had previously received 3 or more lines of therapy, while 46% had received 2 prior lines.
Additionally, patients in the investigative arm had a median exposure to treatment of 13.0 months (range, 0.2-37.0), while those in the control arm had a median exposure of 5.0 months (range, <0.1-6). In this subset, duvelisib elicited an ORR of 78% compared with 39% with ofatumumab.
In DYNAMO, a total of 83 patients comprised the follicular lymphoma cohort; these patients were refractory to rituximab (Rituxan) and either chemotherapy or radioimmunotherapy. The median age in this subset was 64 years (range, 30-82), 68% were male, and 37% had bulky disease at baseline, defined as target lesions of 5 cm or larger. The majority, or 93%, had an ECOG performance status of either 0 or 1. The median prior lines of treatment was 3 (range, 1-10) and 94% of patients were refractory to their last therapy; 81% were refractory to at least 2 previous lines of treatment. Patients were exposed to treatment for a median of 5 months (range, 0.4-24).
Additional results indicated that 35 patients responded to treatment; this included 1 complete response and 34 partial responses. At 6 months, 43% of patients were still experiencing a response; 17% maintained their response at 12 months.
Regarding safety, the most frequent all-grade toxicities experienced with duvelisib include diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.
“The benefits of [duvelisib] are that it prolongs the survival time without any progression of the disease as compared to ofatumumab in patients with CLL who have received 2 or more prior lines of treatment and induces tumor responses in patients with follicular lymphoma who have received 2 or more prior treatment,” the EMA summary stated. “The most common adverse effects are respiratory tract infections, neutropenia, anemia, thrombocytopenia, headache, dyspnea, cough, decreased appetite, diarrhea/colitis, nausea, vomiting, abdominal pain, constipation, rash, musculoskeletal pain, arthralgia, pyrexia, fatigue, and increased transaminases.”
In September 2018, the FDA approved duvelisib for the treatment of patients with relapsed/refractory CLL/SLL or relapsed/refractory follicular lymphoma based on data from DUO and DYNAMO.