Fixed-Duration, All-Oral Ibrutinib plus Venetoclax Regimen Achieves 95% Progression-Free Survival at 2 Years in First-Line CLL Treatment

May 21, 2021 /BioonBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced the initial data from the fixed-duration cohort of the Phase II CAPTIVATE (PCYC-1142, NCT02910583) study. Results showed: receiving the targeted anticancer drugImbruvica(Chinese brand name: Imbruvica®, generic name: ibrutinib) in combination withVenclexta(Chinese brand name: Venclexta®, generic name: venetoclax)Fixed-Duration Regimen for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)Among patients,95% remained alive and progression-free at 2 years.。Deep responses were observed in all subgroups, including patients with high-risk CLL。

Imbruvica (Yike®) is an oral BTK inhibitor co-developed and commercialized by Johnson & Johnson and AbbVie. Venclexta (Weikela®) is an oral BCL-2 inhibitor co-developed and commercialized by AbbVie and Roche.In China, both of these drugs have been approved., relevant information can be found on the official websites of Janssen Pharmaceuticals and AbbVie, respectively.

Imbruvica and Venclexta have complementary mechanisms of action.The positive results of the CAPTIVATE study confirmedImbruvica and Venclexta, as a once-daily, all-oral, fixed-duration combination regimen, offer the potential for deep remission and can be administered in an outpatient setting for younger, fit patients.

Chronic Lymphocytic Leukemia (CLL, Image source: dxline.info)

At a median follow-up of 27.9 months, in the overall patient population,The complete response rate (CR) was 56%.(n=88, 95% CI: 48-64), consistent in the high-risk subgroup. Among patients who achieved CR, 89% maintained a durable CR for at least one year; among the remaining 11%, 1 patient experienced disease progression, and the remaining patients with less than one year of follow-up for remission were not evaluable.

The overall response rate (ORR) was 96%.. Among patients receiving the fixed-duration regimen of Imbruvica + Venclexta, the estimated 24-month progression-free survival (PFS) rate was 93% (95% CI: 85-97) in patients with unmutated IGHV and 95% (95% CI: 88-99) in patients with mutated IGHV. Among all treated patients,24-month overall survival (OS) rate was 98%(95% CI: 94–99). 77% and 60% of patients achieved undetectable minimal residual disease (uMRD) in peripheral blood and bone marrow, respectively, at any time point.

It is worth noting that,`94% with high baseline tumor burden`TumorPatients at risk for tumor lysis syndrome (TLS) transitioned to intermediate or low risk following induction therapy with Imbruvica., no TLS events occurred. Adverse events (AE) were primarily grade 1/2.1 The most common grade 3/4 adverse events were neutropenia (33%), infection (8%),Hypertension(6%) and decreased neutrophil count (5%). The frequency of discontinuation due to adverse events was low (3% for Imbruvica).

Principal Investigator of the CAPTIVATE Study, Medicine, Vita-Salute San Raffaele University, Italy`Tumor`Professor Paolo Ghia stated: "Continuous treatment with Imbruvica in CLL has been established as the standard of care for patients, including those with high-risk disease. The latest data from the CAPTIVATE study highlight,The all-oral, fixed-duration Imbruvica + Venclexta regimen enables patients to achieve treatment-free remission (TFR) while also yielding a high progression-free survival rate at 2 years.。”

In China, ibrutinib (IMBRUVICA®) was first approved in August 2017., as a monotherapy, is indicated for the treatment of: (1) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least one prior therapy; (2) patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.In November 2018, Imbruvica was approved for a new indication.: (1) As monotherapy for patients with Waldenström's macroglobulinemia (WM) who have previously received at least one prior therapy, or as first-line treatment for patients who are ineligible for chemoimmunotherapy; (2) In combination with rituximab for the treatment of patients with WM.

In China, venetoclax (Venclexta®, venetoclax) was approved in December 2020., in combination with azacitidine for the treatment of patients unfit for intensive induction chemotherapy due to comorbidities, or newly diagnosed patients aged 75 years and olderDiagnosisadult patients with acute myeloid leukemia (AML).Venetoclax (Venclexta®, venetoclax) is the first B-cell lymphoma 2 (BCL-2) inhibitor approved in China., marking the entry of China's AML field into the era of targeted therapy. (Bioon.com)