Supplemental New Drug Application for Ibrutinib, Rituximab Combo Submitted to FDA for First-Line Treatment of CLL

A supplemental New Drug Application (sNDA) was submitted to the FDA for ibrutinib (Imbruvica, AbbVie) in combination with rituximab for the first-line treatment of younger patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The application is based on results from the Phase 3 E1912 study that showed a significant improvement progression-free survival (PFS) and overall survival (OS) in patients treated with ibrutinib compared to those treated with fludarabine, cyclophosphamide, and rituximab (FCR).

The E1912 study evaluated 529 previously untreated patients with CLL aged 70 or younger, each randomly assigned to receive ibrutinib plus rituximab or the chemoimmunotherapy. At a median follow-up of 33.6 months, the results of the PFS analysis favored ibrutinib plus rituximab over chemoimmunotherapy (89.4% versus 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), according to the study. The results of the OS analysis also favored ibrutinib plus rituximab over chemoimmunotherapy (98.8% versus 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001).

Additionally, the study included a subgroup analysis of patients without immunoglobulin heavy-chain variable region (IGHV) mutation. In this subgroup, ibrutinub plus rituximab resulted in better PFS than chemoimmunotherapy (90.7% versus 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50)

Ibrutinib is a once-daily, Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally. By blocking BTK, ibrutinib helps move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.

Reference

1. AbbVie submits supplemental new drug application to U.S. FDA for IMBRUVICA® (ibrutinib) in combination with rituximab for the treatment of previously untreated, younger adults with chronic lymphocytic leukemia [news release]. AbbVie's website. https://news.abbvie.com/news/press-releases/abbvie-submits-supplemental-new-drug-application-to-us-fda-for-imbruvica-ibrutinib-in-combination-with-rituximab-for-treatment-previously-untreated-younger-adults-with-chronic-lymphocytic-leukemia.htm. Accessed November 8, 2019.

2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. New England Journal of Medicine. 2019. Doi: 10.1056/NEJMoa1817073.