FDA Approves Imbruvica's 11th Indication: Ibrutinib Plus Rituximab as First-Line Treatment for CLL/SLL

On April 21, AbbVie announced that the U.S. Food and Drug Administration (FDA) had approved Imbruvica (ibrutinib) in combination with rituximab for the first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This marks the 11th indication for Imbruvica since its launch in 2013, and the sixth approval for ibrutinib in CLL indications.

This FDA approval was primarily based on the results of the landmark Phase III E1912 study. The FDA expedited the review process for this application through various pathways, including Real-Time Oncology Review (RTOR), Priority Review, and Project Orbis. The E1912 study enrolled 529 previously untreated patients with chronic lymphocytic leukemia (CLL) under 70 years of age (median age: 58 years), who were randomized in a 2:1 ratio to receive either Imbruvica plus rituximab (n=354) or fludarabine plus cyclophosphamide plus rituximab (FCR, n=175).

The results showed that Imbruvica plus rituximab significantly prolonged progression-free survival (PFS) compared with the FCR regimen. At a median follow-up of 37 months, Imbruvica plus rituximab reduced the risk of disease progression by 66% compared with the FCR regimen (HR=0.34, 95% CI: 0.22-0.52; p <0.0001). At a median follow-up of 49 months, overall survival (OS) data were not yet mature; 11 patients (3%) had died in the Imbruvica plus rituximab group, and 12 patients (7%) had died in the FCR treatment group.

Regarding safety, compared with patients receiving the FCR regimen, the most common adverse reactions of all grades (incidence ≥30%) in the Imbruvica plus rituximab treatment group included fatigue (80% vs 78%), musculoskeletal pain (61% vs 35%), diarrhea (53% vs 27%), rash (49% vs 29%), hypertension (42% vs 22%), arthralgia (41% vs 10%), nausea (40% vs 64%), headache (40% vs 27%), bruising (36% vs 4%), cough (32% vs 25%), and hemorrhage (31% vs 8%).

Brian Koffman, Chief Medical Officer and Executive Vice President of the CLL Society, stated, “For many patients with chronic lymphocytic leukemia (CLL), intravenous chemotherapy has long been the gold standard for first-line clinical treatment; however, many patients are unable to tolerate chemotherapy regimens. The FDA’s approval of the ibrutinib plus rituximab regimen is undoubtedly welcome news for patients seeking non-chemotherapy first-line treatment options. This approval will also drive a shift in the clinical management of younger patients with CLL.”

Ibrutinib was approved by the FDA in January 2019, in combination with Gazyva (obinutuzumab), for the first-line treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marking the first chemotherapy-free first-line combination therapy for CLL approved by the FDA.