FDA has approved Imbruvica (ibrutinib) in combination with rituximab for the treatment of previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.
AbbVie sponsors Imbruvica.
“The FDA approval of ibrutinib and rituximab regimen is welcome news for these previously untreated patients who have been looking forward to a non-chemotherapy treatment option. The results from ECOG-ACRIN’s E1912 clinical trial in previously untreated, younger adult patients and today’s milestone represent a paradigm shift in how physicians can treat patients with CLL and may enable many to choose a non-chemotherapy treatment option,” Brian Koffman, chief medical officer and executive vice president of CLL Society, said in a statement.
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.
In addition to the Real-Time Oncology Review pilot program and priority review, the approval was granted under the FDA’s recently established Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for submission and review of oncology medicine applications among multiple regulatory agencies worldwide.
For this application, a modified Project Orbis was undertaken because of the timing of submission to other regulatory agencies. FDA is collaborating with the Australian Therapeutic Goods Administration, Health Canada, and Swissmedic as they review the application.
“Imbruvica enables long-term disease management and now has demonstrated superior progression-free survival compared to a standard chemoimmunotherapy regimen. Today, many patients who were previously considered appropriate for chemotherapy now have an alternative treatment option,” Danelle James, Imbruvica Clinical Development Lead, Pharmacyclics LLC, an AbbVie company, said in a statement.
The E1912 study demonstrated that previously untreated patients (ages 70 or younger) with CLL have superior progression free survival Imbruvica plus rituximab compared to those treated with fludarabine, cyclophosphamide and rituximab (FCR).
At a median follow-up of 37 months, Imbruvica plus rituximab significantly improved PFS compared to FCR (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.22-0.52; p<0.0001). With a median follow-up time of 49 months, median overall survival was not reached with a total of 23 deaths: 11 (3%) in the IMBRUVICA plus rituximab and 12 (7%) in the FCR treatment arms.
