Priority Review Granted to Combination Therapy for Previously Untreated Subsets of Leukemia & Lympho

The US Food and Drug Administration (FDA) has accepted AbbVie’s supplemental new drug application (sNDA) and granted a priority review for its combination therapy, ibrutinib (IMBRUVICA) in combination with obinutuzumab (GAZYVA), for the treatment of previously untreated adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).

Results from the phase 3 iLLUMINATE (PCYC-1130) trial, which was announced in May 2018, served as the basis for the approval. Results demonstrated that a significantly longer progression-free survival (PFS) was associated with treatment of ibrutinib in combination with obinutuzumab compared to chlorambucil plus obinutuzumab in adults with previously untreated CLL/SLL, according to an assessment by an Independent Review Committee (IRC).

“For the first time in CLL, results from iLLUMINATE have shown the potential benefits of using an IMBRUVICA-based, chemotherapy-free, anti-CD20 combination, “ said Danelle James, M.D., M.A.S., head of clinical science, Pharmacyclics LLC, an AbbVie company, in a recent statement.

As a randomized, multi-center, open-label, phase 3 clinical trial, the iLLUMINATE (NCT 02264574) evaluated ibrutinib in combination with obinutuzumab compared to chlorambucil in combination with obinutuzumab in patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).

Patients with previously untreated CLL or SLL who were aged 65 years and older were enrolled in the study. Patients aged less than 65 years had a minimum of 1 of the following criteria: Cumulative Illness Rating Score (CIRS) >6 and Creatinine clearance estimated <70 mL/min using Cockcroft-Gault equation.

Progression-free survival, as defined by an IRC, served as the primary endpoint. Secondary objectives, which included an overall response rate and a rate of minimal residual disease (MRD)-negative responses, were also assessed.

“Patients were randomized to receive IMBRUVICA 420 mg continuously in combination with obinutuzumab 1000 mg intravenously over 6 cycles or chlorambucil on Days 1 and 15 of each cycle plus obinutuzumab 1000 mg intravenously over 6 cycles.”

Should the sNDA be approved, the ibrutinib/obinutuzumab combination therapy would become the first chemotherapy-free, anti-CD20 combination approved by the FDA for the first-line treatment of CLL/SLL.

"Our robust clinical research program with IMBRUVICA continues to reinforce the evidence for its use as an efficacious treatment option in CLL and SLL, this time versus a National Comprehensive Cancer Network guidelines Category 1 treatment, which is the chemoimmunotherapy combination of chlorambucil plus obinutuzumab," added Dr. James.

Previously, ibrutinib was approved by the FDA for the treatment of adults with CLL/SLL as a single-agent for all lines of therapy and in combination with bendamustine and rituximab (BR).

Ibrutinib, a once-daily, first-in-class Bruton's tyrosine kinase (BTK) inhibitor, is administered orally.

Both CLL and SLL are biologically similar in that they are both characterized by an overabundance of immature white blood cells, which cause lymph nodes to become larger than normal. With a median age diagnosis ranging from 65-70 years, CLL/SLL are predominantly diseases of the elderly.