AbbVie's IMBRUVICA® (ibrutinib) Plus VENCLEXTA®/VENCLYXTO® (venetoclax) Combination Achieves 95% Disease-Free Survival at One Year in uMRD Patients with Previously Untreated CLL

December 06, 2020 News /BioValleyBIOON/ -- AbbVie recently announced new data from the Phase II CAPTIVATE (PCYC-1142) study at the 62nd Annual Meeting of the American Society of Hematology (ASH). The study enrolled 164 treatment-naive patients aged 18–70 years with chronic lymphocyticLeukemiaconducted in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), evaluating the efficacy and safety of Imbruvica (ibrutinib) in combination with Venclyxta/Venclyxto (venetoclax) as first-line treatment.

In the study, patients received three cycles of ibrutinib lead-in therapy, followed by twelve cycles of combination therapy with ibrutinib plus venetoclax (ibrutinib 420 mg/day; venetoclax titrated up to 400 mg/day). Upon completion of the twelve cycles of ibrutinib plus venetoclax treatment, patients confirmed to have undetectable minimal residual disease (uMRD, i.e., MRD-negative)—defined as achieving uMRD in both peripheral blood (PB) and bone marrow (BM) for more than three consecutive cycles—were randomized in a 1:1 ratio to receive double-blind treatment with either placebo or ibrutinib. Patients who did not achieve uMRD were randomized in a 1:1 ratio to receive open-label treatment with either ibrutinib alone or ibrutinib plus venetoclax. Undetectable minimal residual disease (MRD-negative) indicates that cancer cells are not detectable after treatment using a specialized, highly sensitive assay, defined as fewer than one cancer cell per 10,000 white blood cells.

Results presented at the conference showed that treatment with the ibrutinib plus venetoclax regimen achieved deep responses, with a 30-month progression-free survival (PFS) rate of approximately 95% across all treated patients, including the subset of patients who were randomized to placebo after completing 12 cycles of therapy. One-year disease-free survival (DFS) data from patients who completed the combination regimen and were then randomized to either placebo or Imbruvica supported that this fixed-duration approach can provide CLL/SLL patients with a period of remission and treatment-free interval.

The results presented at the conference build upon previously reported findings, namely that this first-line combination regimen achieved high rates of undetectable minimal residual disease (uMRD, i.e., MRD negativity) in patients with chronic lymphocytic leukemia (CLL), both in peripheral blood (PB: 75% of patients) and bone marrow (BM: 72% of patients). Among patients with confirmed uMRD, there was no statistically significant difference in one-year disease-free survival (DFS) between those randomized to placebo (95.3%; 95% CI: 82.7–98.8) and those randomized to ibrutinib (100%; 95% CI: 100–100) (p=0.1475).

Throughout the study period, among all treated patients (median treatment duration: 29 months), the most common grade 3/4 adverse events (occurring in ≥5% of patients) were neutropenia (36%),Hypertension(10%), thrombocytopenia (5%), and diarrhea (5%). The safety profile of the combination therapy was consistent with the known adverse events associated with ibrutinib and venetoclax, with no new safety signals identified.

William Wierda, M.D., Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, stated, “These results indicate that the combination of ibrutinib and venetoclax can provide patients with CLL/SLL with sustained disease-free survival once treatment is completed. It is very exciting for patients to have a potential option in the future that allows them to achieve remission and take a treatment break.”

Imbruvica is a first-in-class, once-daily oral Bruton’s tyrosine kinase (BTK) inhibitor, jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech, Inc., a Johnson & Johnson company. The drug exerts its anticancer effects primarily by inhibiting BTK, which is required for the proliferation and metastasis of cancer cells. BTK is a key signaling molecule in 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 is capable of blocking the signaling pathways that mediate uncontrolled proliferation and dissemination of B cells, helping to kill cancer cells and reduce their numbers, thereby delaying cancer progression. InClinical Trialmonotherapy and combination therapies for a broad range of hematologic malignanciesTumorDemonstrated robust efficacy.

Since its market launch in 2013, Imbruvica has received 11 approvals across a total of six indications, including five B-cell hematologic malignancies and chronic graft-versus-host disease (cGVHD).FDAApproved indications: Chronic lymphocytic leukemia (CLL) with or without deletion 17p [del(17p)] mutation; small lymphocytic lymphoma (SLL) with or without deletion 17p [del(17p)] mutation; Waldenström macroglobulinemia (WM); previously treated mantle cell lymphoma (MCL); marginal zone lymphoma (MZL) requiring systemic therapy and having received at least one prior anti-CD20 regimen; chronic graft-versus-host disease (cGVHD) following failure of one or more lines of systemic therapy.

Currently, AbbVie and Johnson & Johnson are advancing a large-scale Imbruvica clinicalTumorProject Development. The industry holds a highly optimistic view of Imbruvica’s commercial prospects. In January this year, an article titled “Top product forecasts for 2020,” published in the prestigious international journal Nature Reviews Drug Discovery, predicted that Imbruvica’s global sales would reach $6.818 billion in 2020. In late June, the pharmaceutical market research firm EvaluatePharma released a forecast report stating that, with continuous market penetration and an expanding range of indications, Imbruvica’s sales are projected to reach $10.722 billion by 2026, making it the fifth best-selling drug worldwide. (Bioon.com)

Original Source: IMBRUVICA® (ibrutinib) Plus VENCLEXTA®/VENCLYXTO® (venetoclax) Combination Shows High Rates of Disease-Free Survival One Year Post-Treatment in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL)