Earlier Treatment with Imbruvica (Ibrutinib) Monotherapy in CLL Yields Superior Long-Term Outcomes, New Integrated Analysis Shows

December 10, 2019 /Bio ValleyBIOON/ -- The 61st Annual Meeting of the American Society of Hematology (ASH 2019) was recently held in Orlando, Florida, USA. ThisMeetingAbove, AbbVie and Johnson & Johnson (JNJ) announced the use of the targeted anticancer drug Imbruvica® (Chinese brand name: Yike®, generic name: ibrutinib) for the treatment of chronic lymphocyticLeukemiaNew Comprehensive Analysis of Long-Term Follow-Up Data from Two Phase III Studies (RESONATE, RESONATE-2) in Chronic Lymphocytic Leukemia (CLL). The data demonstrate improved outcomes with early-line (first-line) treatment of CLL using Imbruvica.

Imbruvica is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor administered orally once daily, jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech, Inc., a Johnson & Johnson company.

This new comprehensive analysis evaluated the long-term efficacy of Imbruvica as monotherapy for early treatment in patients with chronic lymphocytic leukemia (CLL). The analysis included previously untreated CLL patients (first-line group, n=136; median age: 73 years) and those with relapsed or refractory CLL (R/R group, n=135; median age: 65 years). Results showed that, compared to the R/R group, Imbruvica monotherapy demonstrated improved progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in the first-line group, including patients with high-risk prognostic features.

Specific data are as follows: (1) During a follow-up period of up to 6 years (first-line group: median duration 59.8 months; 1–2 prior lines of therapy group: median duration 66.2 months; ≥3 prior lines of therapy group: median duration 65.1 months), the median progression-free survival (PFS) was not reached in the first-line group and the 1–2 prior lines of therapy group, whereas the median PFS in the ≥3 prior lines of therapy group was 40.1 months. (2) Among patients with chronic lymphocytic leukemia (CLL) who received Imbruvica earlier in their treatment course, a higher proportion remained progression-free or alive at 60 months (first-line group: 70%; 1–2 prior lines of therapy group: 60%; ≥3 prior lines of therapy group: 33%). (3) Compared with the 1–2 prior lines of therapy group, first-line therapy reduced the risk of disease progression or death by 34% (HR=0.66, 95% CI: 0.40–1.09). (4) Compared with the ≥3 prior lines of therapy group, first-line therapy reduced the risk of disease progression or death by 68% (HR=0.32, 95% CI: 0.21–0.49). (5) Regarding overall survival (OS), the median OS was not reached in either the first-line group or the 1–2 prior lines of therapy group, while the median OS in the ≥3 prior lines of therapy group was 67.4 months. (6) Regarding overall response rate (ORR), at 60 months, the rates were 92%, 96%, and 88% in the first-line group, the 1–2 prior lines of therapy group, and the ≥3 prior lines of therapy group, respectively.

At the time of analysis, 58% of patients in the first-line group were still receiving Imbruvica treatment. Overall, 6% of patients in the first-line group discontinued treatment due to progressive disease, whereas progressive disease was the most common reason for discontinuation in the group with 1–2 prior therapies (22%) and the group with ≥3 prior therapies (37%). Across all three groups, 19% of patients discontinued treatment due to adverse events (first-line group: 21%; 1–2 prior therapies group: 19%; ≥3 prior therapies group: 15%).

These results provide new clinical evidence supporting the use of Imbruvica in early-stage treatment of chronic lymphocytic leukemia (CLL) to improve patient outcomes, whereas chemoimmunotherapy had previously been the standard approach for early-stage CLL treatment.

Imbruvica is a small-molecule drug administered orally once daily. It exerts its anticancer effects primarily by inhibiting Bruton’s tyrosine kinase (BTK), which is essential for the proliferation and metastasis of cancer cells. BTK is a key signaling molecule within the B-cell receptor signaling complex and plays a critical role in the survival and metastasis of malignant B cells, as well as in various other serious debilitating diseases.

Imbruvica blocks the signaling pathways that mediate uncontrolled proliferation and dissemination of B cells, helping to kill cancer cells and reduce their number, thereby delaying cancer progression. InClinical Trialin, monotherapy and combination therapies targeting a broad range of hematologic malignanciesTumorDemonstrated robust efficacy.

Since its launch in 2013, Imbruvica has obtained 10 approvals across a total of six indications, including five B-cell hematologic malignancies and chronic graft-versus-host disease (cGVHD).FDAApproved: Chronic lymphocytic leukemia (CLL) with or without 17p deletion mutation (del17p), small lymphocytic lymphoma (SLL) with or without 17p deletion mutation (del17p), Waldenström macroglobulinemia (WM), previously treated mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) requiring systemic therapy and having received at least one anti-CD20 therapy, and chronic graft-versus-host disease (cGVHD) that has failed treatment with one or more systemic therapies.

Currently, AbbVie and Johnson & Johnson are advancing a large-scale Imbruvica clinicalTumorDevelopment Project. The industry holds a highly optimistic view of the commercial prospects for Imbruvica. In June this year, the pharmaceutical market research firm EvaluatePharma released a report stating that Imbruvica’s global sales reached $4.454 billion in 2018, and with continuous market penetration and an expanding range of indications, global sales are projected to reach $9.514 billion by 2024. (Bioon.com)

Original Source:Extended Follow-up Phase 3 Data Underscore Sustained Efficacy and Safety of IMBRUVICA® (ibrutinib) in the Treatment of Chronic Lymphocytic Leukemia (CLL)