Crossover Study Offers Additional Line of Therapy for Patients with Relapsed CLL/SLL

Single agent Copiktra (duvelisib) induced robust, durable responses in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who experienced disease progression after treatment with Arzerra (ofatumumab) alone, according to data from the DUO crossover extension study.

In the phase 3 study, patients treated with Copiktra demonstrated a significant improvement in progression-free survival — or the time to disease progression or worsening – compared with those treated with Arzerra (median, 13.3 months vs. 9.9 months). In addition, the agent showed a manageable safety profile.

“This (trial) led to the (Food and Drug Administration) approval of the drug back in September,” study author Matthew S. Davids, M.D., MMSc, noted in an interview with CURE.

In this open-label, optional, crossover extension study — presented at the 2018 American Society of Hematology (ASH) Annual Meeting – Davids reported on data for the 90 patients who crossed over following disease progression on Arzerra and went on to receive 25 mg of Copiktra twice daily until disease progression, intolerance, death, or study withdrawal.

Median age was 68 years, and the majority of patients were male (63 percent) and white (90 percent). Patients received a median of three therapies prior to Copiktra, with 60 percent who were given three or more prior anticancer therapies.

The median progression-free survival after patients crossed over to Copiktra was 15 months, compared with nine months before patients crossed over. Of note, this was significant among those with a 17p deletion (17 months vs. eight months, respectively).

Similarly, overall response rates were higher in patients after treatment crossover compared with before (77 percent vs. 29 percent), and again in the 17p deletion subset (80 percent vs. 15 percent).

Forty-seven patients experienced no response prior to crossover. The overall response rate in this group was 73 percent after treatment with Copiktra.

Patients treated with Copiktra achieved rapid lymphocytosis (median, 1.1 months) with a median time to first response of 2.6 months.

The most common severe hematologic side effects with Copiktra included neutropenia (23 percent) and thrombocytopenia (4 percent). The most common severe non-hematologic side effects were diarrhea (21 percent), pneumonia (12 percent), colitis (11 percent), lipase increased (7 percent), acute renal failure (6 percent), and bronchitis, rash and sepsis (4 percent, each).

About 70 percent of patients had dose modifications due to side effects, most commonly from diarrhea (27 percent), pneumonia (10 percent), colitis (8 percent), neutropenia and lipase increased (7 percent each). Events of colitis (10 percent), diarrhea (9 percent), pneumonia (2 percent) and rash (2 percent) led to treatment discontinuation.

“(Copiktra) is an effective treatment option for patients with relapsed CLL after two or more lines of therapy,” said Davids, who is the associate director of the Center for Chronic Lymphocytic Leukemia at Dana Farber Cancer Institute in Boston. “Patients may receive other lines of therapy like (Arzerra) and then go on to get (Copiktra) and still do very well. So, I think even though we have many therapeutic options in CLL, it is always important to have new options, and I think this is a good one for our CLL patients.”