[Lymphoma Microcourse 2021EHA] EP636 First-line Treatment of Ibrutinib in Patients with Chronic Lymphocytic Leukemia: 7-year follow-up of the RESONATE-2 study

Fellow fellows, hello everyone! Welcome to the "Lymphoma Microclass"
.

I am Dr.
Qian Shenxian from Hangzhou First People's Hospital affiliated to Zhejiang University School of Medicine
.

Today I will mainly introduce an abstract on EHA in 2021: First-line treatment of Ibrutinib in patients with chronic lymphocytic leukemia: 7-year follow-up of the RESONATE-2 study
.

Ibrutinib is a BTK inhibitor that is taken orally once a day and has been approved for the treatment of adult chronic lymphocytic leukemia (CLL) in many countries and regions around the world
.

In multiple randomized phase 3 studies, compared with existing chemotherapy/chemo-immunotherapy regimens, ibrutinib is the only one that has been shown to significantly prolong the absence of patients with newly treated CLL/small lymphocytic lymphoma (SLL) Targeted therapy drugs for progressive survival (PFS) and overall survival (OS)
.

 The RESONATE-2 study included a total of 269 CLL/SLL patients aged ≥65 years, without del(17p) mutations and previously untreated
.

Patients were randomly assigned at a ratio of 1:1 and received ibrutinib (420 mg) monotherapy once a day until the disease progressed or an intolerable adverse reaction (n=136) occurred or received up to 12 cycles of benzene Chlormus butyrate (0.
5-0.
8 mg/kg) treatment (n=133)
.

The long-term results of the study include PFS, OS, total effective rate (ORR), and safety
.

The researchers evaluated the efficacy according to the 2008 iwCLL standard
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 Overall, after 7 years of follow-up, compared with chlorambucil, patients treated with ibrutinib continued to benefit significantly from PFS (HR: 0.
160, CI: 0.
111-0.
230), and patients received an average of 74.
9 Months of treatment (range 0.
1-86.
8 months)
.

In addition to the overall population, a subgroup of patients with high-risk genomic characteristics (including IGHV non-mutation (HR: 0.
109 [95%CI: 0.
063-0.
189]) and del(11q) (HR: 0.
033[95%CI: 0.
010-0.
107] In )), significant benefits were also observed in the PFS of patients in the Ibrutinib group
.

 At 6.
5 years of treatment, 61% of patients treated with ibrutinib and 9% of patients treated with chlorambucil had no disease progression
.

The 6.
5-year OS rate of patients in the ibrutinib group was 78%
.

 In the current follow-up, the ORR of patients receiving ibrutinib was 92%, and the complete remission (CR/CRi) rate reached 34%
.

The adverse events (AEs) of patients in the ibrutinib group are as follows: The incidence of ≥3 grade hypertension was 5% (n=4) after 5-6 years of treatment, and 4% during 6-7 years of treatment ( n=3); the incidence of grade ≥3 atrial fibrillation after 5-6 years of treatment is 1% (n=1), and after 6-7 years of treatment, the incidence is 1% (n=1); treatment for 5-7 years There were no major bleeding events of grade ≥3, and it can be seen that the incidence of ibrutinib-related grade ≥3 hypertension, atrial fibrillation, and major bleeding is relatively low in patients with long-term follow-up
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At 5-6 years and 6-7 years of treatment, 1% (n=1) of patients reduced the dose due to adverse events
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During the 8-year follow-up period, there were 31 patients whose dose was reduced due to adverse events of any grade, and 71% (22/31) of the patients were relieved or improved
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After 5-6 years of treatment, 3% (n=2) of patients discontinued the drug due to adverse events of any grade, while no patients discontinued the drug due to adverse events at 6-7 years
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Disease progression is the main reason for discontinuation after 5-6 years of treatment (5%, n=4) and 6-7 years (6%, n=4)
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After 7 years of follow-up, 47% of patients continued to receive Ibrutinib monotherapy
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Conclusion: Long-term follow-up of newly treated CLL/SLL patients, including patients with high-risk genomic characteristics, through the RESONATE-2 study confirmed that Ibrutinib can continue to bring PFS and OS benefits to patients
.

As the treatment time prolonged, the patient's relief continued to deepen
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Follow-up data for up to 7 years showed that the incidence of Ibrutinib-related adverse events ≥ grade 3 was low
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Due to the low incidence of discontinuation of treatment and dose reduction of AEs, most AEs were relieved or improved after dose reduction
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No new safety signals were observed, and Ibrutinib was well tolerated
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 Thank you for watching today's "Lymphoma Microclass"! Professor Qian Shenxian, Executive Vice President, Chief Physician, Professor, and Ph.
D Supervisor of Hangzhou First People's Hospital, Zhejiang University School of Medicine, Deputy Director, Zhejiang Provincial Medical Association Hematology Branch Deputy Director, Zhejiang Medical Association Internal Medicine Branch, Zhejiang Anticancer Deputy Director of the Hematology Branch of the Association, Deputy Director of the Hematology Branch of the Zhejiang Society of Immunology, Deputy Director of the Hematology Branch of the Zhejiang Medical Association, Deputy Director of the Hematology Branch of the Zhejiang Medical Association Director, City of Hope Visiting Scholar of the American Medical Center, presided over more than 10 national, provincial and municipal topics, published more than 160 papers, and more than 20 SCI papers
.

Won a number of provincial and municipal science and technology awards; Chinese physician award and Hangzhou's first "Germany and technology double xin famous doctor" title Reference materials: Paolo Ghia, et al.
EP636 EHA 2021.
IBRUTINIB TREATMENT IN THE FIRST-LINE SETTING FOR PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA : UP TO 7 YEARS OF FOLLOW-UP IN THE RESONATE-2 STUDYCRC: MED-ONC-CN-2202, Approved on 2021-05-27 stamp "Read the original", we make progress together