Professor Li Jianyong: Diagnosis and Treatment of Chronic Lymphocytic Leukemia The 16th National Leukemia and Lymphoma Academic Conference

Sponsored by the Chinese Medical Association, Hematology Branch of Chinese Medical Association, Leukemia and Lymphoma Group of Hematology Branch of Chinese Medical Association, Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences), First Affiliated Hospital of University of Science and Technology of China The 16th National Leukemia and Lymphoma Academic Conference hosted by the Chinese Medical Association will be held in Hefei, Anhui Province on October 8-10, 2021
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At this conference, Professor Li Jianyong from the First Affiliated Hospital of Nanjing Medical University gave a theme report on "Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL)".
Yimaitong organized the main contents as follows
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Professor Li Jianyong first introduced the basic situation of CLL
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Compared with European and American countries, the incidence of CLL/Small Lymphocytic Lymphoma (SLL) in China is relatively low, but the number of new cases of CLL/SLL in China is on the rise every year
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With the continuous improvement of the level of diagnosis and treatment of CLL, the survival of CLL patients has been continuously improved.
The 10-year overall survival (OS) rate of CLL patients in China has increased from 51.
6% in 1985 to 75% in 2009
.

The diagnosis and prognosis evaluation of CLL Professor Li Jianyong then introduced the diagnosis and prognosis evaluation of CLL
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Professor Li Jianyong said that since CLL and SLL use different disease staging and efficacy evaluation methods, misdiagnosis of the two diseases should be avoided
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Monoclonal B lymphocytosis (MBL) may also be misdiagnosed as CLL.
The diagnosis should be based on the patient's peripheral blood B lymphocyte level, lymph node status, and blood cell reduction due to bone marrow infiltration to distinguish CLL, SLL, and MBL
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In addition, it is necessary to analyze the IGHV-DJ gene rearrangement when CLL undergoes disease transformation, determine the relationship between RS/RT and the original CLL clone, and determine whether the disease transformation is related to the clone
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Professor Li Jianyong emphasized that genetic testing is required for prognostic evaluation of CLL patients to observe the patient's TP53 mutation and del(17p)
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In addition to TP53 gene abnormalities, BIRC3 mutations, BRAF mutations, and NOTCH1 mutations are also poor prognostic factors for CLL, which play an important role in guiding CLL patients when adjusting treatment plans
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The treatment progress of CLL Professor Li Jianyong then introduced the treatment progress of CLL
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CLL patients need to be treated according to the indications for treatment (including massive lymphadenopathy, progressive lymphocytosis, etc.
)
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Professor Li Jianyong emphasized that the lymphocyte doubling time (LDT) alone should not be used as a treatment indication for CLL patients with newly-treated lymphocytes less than 30×109/L
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For patients there is no indication of treatment, need every 2-6 months follow-up, blood test carried out at the same time to determine whether patients with clinical symptoms, such as swollen lymph nodes, liver and spleen appear
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Progress in the treatment of newly-treated CLL In recent years, new small-molecule targeted drugs have made significant progress in CLL.
Long-term BTK inhibitor-free chemotherapy has completely replaced the status of immunochemotherapy in the treatment of CLL
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The long-term follow-up results of the RESONATE-2 study showed that after 8 years of treatment with ibrutinib, the complete remission (CR) rate of newly-treated CLL patients still reached 34%, and only 6% of patients discontinued the drug due to disease progression
.

In addition, the therapeutic benefits of ibrutinib are not affected by del(11q) (HR: 0.
033; 95% CI: 0.
010-0.
107), IGHV non-mutation (HR: 0.
109; 95% CI: 0.
063-0.
189), etc.
The influence of prognostic factors
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In addition, the safety of ibrutinib in the first-line treatment of CLL patients is good, and the incidence of adverse events ≥ grade 3 related to ibrutinib in the study is relatively low
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 A study published in 2020 explored the efficacy of ibrutinib in the treatment of newly treated CLL patients with abnormal TP53
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The results of the study showed that for CLL patients with both abnormal TP53 and non-mutation of IGHV, the progression-free survival (PFS) after treatment with Ibrutinib was still relatively short
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In order to further overcome the poor prognostic factors of CLL patients, related studies have explored the efficacy of Ibrutinib combined regimen in CLL patients
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The Phase III ALLIANCE study explored the efficacy of ibrutinib combined with rituximab in newly-treated elderly (≥65 years) CLL patients.
Butinib alone did not further prolong PFS and OS in CLL patients (HR: 1.
00; P=0.
49)
.

 The ELEVATE-TN study compared the efficacy of the BTK inhibitor Acalabrutinib combined with otuzumab, otuzumab combined with chlorambucil, and Acalabrutinib as a single agent in the first-line treatment of CLL patients
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The results of the study showed that at a median follow-up time of 46.
9 months, compared with Acalabrutinib alone, Acalabrutinib combined with otuzumab regimen and otuzumab combined with chlorambucil regimen both prolonged the PFS of newly treated CLL patients (4-year PFS rate: 87% vs 78% vs 25%)
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However, a subgroup analysis of the study showed that for patients with CLL without IGHV mutations, the combination of octuzumab and chlorambucil resulted in limited prolongation of PFS in CLL patients compared with Acalabrutinib alone
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The progress of treatment of relapsed and refractory CLL Professor Li Jianyong then introduced the progress of treatment of relapsed and refractory CLL
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The therapeutic prospects of new BTK inhibitors in relapsed and refractory CLL/SLL are worthy of attention
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The results of a study exploring the treatment of relapsed and refractory CLL/SLL with a new BTK inhibitor Zebutinib showed that at a median follow-up of 34 months, the CR rate of Zebutinib in the treatment of relapsed and refractory CLL/SLL reached 13.
2%
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In addition, the clinical benefit brought by zebutinib for patients with relapsed and refractory CLL/SLL can also overcome adverse prognostic factors such as del(17p) and TP53 mutations
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 The new BTK inhibitor abutinib also showed excellent efficacy in relapsed and refractory CLL/SLL
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At a median follow-up of 25.
6 months in related studies, the overall response rate (ORR) of abutinib in the treatment of relapsed and refractory CLL/SLL reached 93.
8%, the CR rate reached 21.
3%, the 18-month PFS rate reached 78.
7%, and 77.
2% The patient's duration of remission (DOR) reached 18 months
.

 The therapeutic prospect of the non-covalently bound BTK inhibitor LOXO-305 in relapsed and refractory CLL/SLL is also worth looking forward to
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The results of the Phase I/II BRUIN study showed that at a median follow-up of 6 months, the ORR of LOXO-305 in patients with relapsed and refractory CLL/SLL reached 63%
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For patients with relapsed and refractory CLL/SLL who have failed previous BTK inhibitor therapy, LOXO-305 is expected to provide a new treatment option
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 Another study compared the efficacy of different BTK inhibitors in patients with relapsed and refractory CLL/SLL
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The ELEVATE-RR study compared the efficacy of Ibrutinib and Acalabrutinib in the treatment of relapsed and refractory CLL/SLL.
At a median follow-up of 40.
9 months, the median PFS of both groups was 38.
4 months.
Acalabrutinib was compared with Ibrahimovic.
Tinib showed non-inferiority in efficacy (HR: 1.
00)
.

The safety of the two BTK inhibitors in patients with relapsed and refractory CLL/SLL is similar, and the incidence of adverse events (AE) of any grade and AE ≥ grade 3 are similar
.

Application of fixed course of treatment in CLL Although BTK inhibitors bring long-term survival for CLL patients, most patients require long-term medication
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Some studies are also exploring the efficacy of a fixed course of treatment in CLL patients.
The CLL14 study explored the efficacy of a fixed course of Bcl-2 inhibitor venaclla combined with otuzumab in newly treated CLL patients
.

The results of the study showed that at a median follow-up of 52.
4 months, the median PFS of venexa combined with otuzumab was not reached, and the estimated 4-year PFS rate was 74%.
Among them, 4 patients with abnormal TP53 and patients without IGHV mutations The annual PFS rates are 53% and 68% respectively
.

Thirty months after the treatment, the peripheral blood was sequenced to evaluate the minimal residual disease (MRD) status.
26.
9% of the patients were still MRD-negative (<10-4)
.

 In view of the excellent efficacy of the fixed-course regimen of venexa and otuzumab in CLL patients, some studies have tried to combine BTK inhibitors on the basis of this regimen to further improve the efficacy
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Relevant research results show that the fixed course of treatment (or MRD level guided withdrawal) of venecla combined with otuzumab and BTK inhibitors (including ibrutinib, zebutinib, and Acalabrutinib) has the same effect in CLL patients Considerable, the CR rate is about 32%-49%
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Summary Professor Li Jianyong finally concluded: For CLL patients who do not have high-risk prognostic factors, both traditional immunochemotherapy regimens and BTK inhibitors can bring better prognosis for patients
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For CLL patients with high-risk prognostic factors, the new drug combination program is expected to overcome high-risk and unfavorable prognostic factors and bring better curative effects to CLL patients
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The fixed course of treatment has shown considerable therapeutic prospects in CLL patients and is expected to become an important treatment option for CLL
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Professor Li Jianyong, Pukou Chronic Lymphoma Center, Jiangsu Provincial People's Hospital, Director of the Department of Hematology, Doctoral Supervisor, and Postdoctoral Cooperative Supervisor, Nanjing Medical University First Affiliated Hospital The 4th Chairman of the Hematology Oncology Committee of the Chinese Anti-Cancer Association, the 5th Honorary Chairman, and the Leader of the Lymphoma Group Leader of the Chinese Chronic Lymphocytic Leukemia Working Group CSCO Vice Chairman of the Chinese Lymphoma Alliance Chinese Medical Association Oncology Branch Lymph Oncology Group Deputy Leader, Jiangsu Geriatrics Association Hematology Branch Chairman, Jiangsu Provincial Medical Association Hematology Branch, Jiangsu Provincial Medical Association Hematology Branch, Former Chairman, Nanjing Medical Association Hematology Branch, Nanjing Medical Association, Hematology Branch, Chinese Medical Doctor Association Integration The deputy chairman of the Hematology Professional Committee stamps "read the original text", and we make progress together