Combination offers ‘important new option’ for CLL, team says

In addition, all subgroups analyzed favored idelalisib—refractory or relapsed disease, mutation status, cytogenetics, gender, age, and race.

Patients with neither deletion 17p nor TP53 had a hazard ratio of 0.22 favoring the idelalisib group, and patients with either one or the other of those mutations had a hazard ratio of 0.50 favoring idelalisib.

ORR was 68% and 45% for idelalisib and placebo, respectively, with 5% in the idelalisib arm and none in the placebo arm achieving a CR.

Dr Zelenetz pointed out that the CR rate was low largely due to missing confirmatory biopsies.

Ninety-six percent of patients in the idelalisib arm experienced 50% or more reduction in lymph nodes, compared with 61% in the placebo arm.

Patients in the idelalisib arm also experienced a significant improvement in OS of P=0.008 when stratified and P=0.023 when unstratified. Median OS has not been reached in either arm.

There was no difference in survival benefit in patients with refractory disease.

Safety

All patients in the idelalisib arm and 97% in the BR arm experienced an adverse event (AE), with 93% and 76% grade 3 or higher in the idelalisib and BR arms, respectively.

Serious AEs occurred in 66% of idelalisib-treated patients and 44% of placebo patients.

Fifty-four patients (26%) in the idelalisib arm discontinued the study drug due to AEs, and 22 (11%) required a study drug dose reduction. This was compared with 28 patients (13%) discontinuing and 13 patients requiring dose reductions in the placebo arm.

The most frequent AE occurring in more than 10% of patients was neutropenia. Grade 3 or higher neutropenia occurred in 60% of idelalisib patients and 46% of placebo patients.

Most AEs were higher in the idelalisib arm compared with the BR arm, including grade 3 or higher events, such as febrile neutropenia (20%, 6%), anemia (15%, 12%), thrombocytopenia (13%, 12%), pneumonia (11%, 6%), ALT increase (11%, <1%), pyrexia (7%, 3%), diarrhea (7%, 2%), and rash (3%, 0), among others.

Serious AEs occurring in more than 2% of patients were also higher in the idelalisib arm than the BR arm, and included febrile neutropenia (18%, 5%), pneumonia (14%, 6%), pyrexia (12%, 6%), neutropenia (4%, 1%), sepsis (4%, 1%), anemia (2%, 2%), lower respiratory tract infection (2%, 2%), diarrhea (4%, <1%), and neutropenic sepsis (1%, 3%).

The remainder of the serious AEs—urinary tract infection, bronchitis, septic shock, and squamous cell carcinoma—occurred in 2% or fewer patients in either arm.

Dr Zelenetz pointed out that the safety profile is consistent with previously reported studies.

Gilead Sciences developed idelalisib and funded Study 115.

*Data in the abstract differ slightly from data presented at the meeting.