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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Monday, April 27, 2020

FDA Approves Ibrutinib Plus Rituximab for Chronic Lymphocytic Leukemia

The FDA expanded the indication of ibrutinib to include its combination with rituximab for the initial treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Approval was based on the E1912 trial (NCT02048813), a 2:1 randomized, multicenter, open-label, actively controlled trial of ibrutinib with rituximab compared to fludarabine, cyclophosphamide, and rituximab (FCR) in 529 adult patients 70 years or younger with previously untreated CLL or SLL requiring systemic therapy. Patients with 17p deletion were excluded. Ibrutinib was administered at 420 mg daily until disease progression or unacceptable toxicity.

The main efficacy outcome measure was progression-free survival (PFS). The trial demonstrated a statistically significant improvement in PFS for patients receiving ibrutinib plus rituximab compared with those receiving FCR (HR 0.34; 95% CI: 0.22, 0.52; p<0.0001). Median PFS was not reached in either arm after a median follow-up duration of 37 months.

The most common adverse reactions (≥30%) in patients with CLL/SLL receiving ibrutinib are thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, and nausea.

The recommended ibrutinib dose is 420 mg taken orally once daily with a glass of water. Rituximab was initiated in Cycle 2 and administered at 50 mg/m2 on Day 1, 325 mg/m2 on Day 2, and 500 mg/m2 on Day 1 of 5 subsequent cycles, for a total of 6 cycles.