Prof. Li Yuhua: Advances and Prospects of Drug Therapy for Indolent Lymphoma 2021 China Oncology Congress

Indolent lymphomas are a group of non-Hodgkin lymphomas (NHLs) with relatively slow clinical progression
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Follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL) are the more common indolent NHLs
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Although indolent lymphoma is not aggressive, it is incurable, easy to relapse, easy to ignore, and easy to transform
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The prognosis of patients with indolent lymphoma after transformation and progression is very poor
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In recent years, many drug studies have achieved remarkable results in indolent lymphoma, so what is the current progress in the treatment of indolent lymphoma? At the 2021 China Conference on Oncology (CCO) held online from April 14 to 17, 2022, Professor Li Yuhua of Pearl River Hospital of Southern Medical University gave the title of "Progress and Prospects of Drug Therapy for Indolent Lymphoma", from FL, MCL, Four aspects of CLL and Waldenström's macroglobulinemia (WM) specifically introduced the treatment progress of indolent lymphoma drugs
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The current status of follicular lymphoma for FL patients.
In recent years, studies have shown that 87% of FL patients eventually require systemic therapy, and only about 6% of FL patients do not need treatment for ≥10 years
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FL is incurable, and the vast majority of patients will relapse and progress multiple times.
For each relapse, the remission time of FL patients decreases, the chance of refractory increases, and the survival period is shortened
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The 5-year survival rate of early progression-free patients is 80%, while the 5-year survival rate of patients with relapse within 24 months of first-line therapy (POD24) is only 50%
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For the treatment of FL, the GLSG2000 study introduced rituximab (R) into the treatment of FL patients for the first time.
Compared with the CHOP regimen, R-CHOP brought better survival benefits to FL patients
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In 2017, the New England Journal published the results of the GALLIUM trial, which compared the efficacy of 1200 patients with otuzumab combined with CHOP regimen (G-CHOP) and R-CHOP regimen.
The data showed that POD24 in the G-CHOP group The risk was reduced by 47.
6%; in the Chinese GALLIUM subgroup analysis, consistent with the global GALLIUM study, the risk of recurrence/progression or death was reduced by 45% in the G-CHOP group
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At present, the NCCN guidelines (2021 v4) and the Chinese Society of Clinical Oncology (CSCO) lymphoma diagnosis and treatment guidelines (2021) both use G-CHOP chemotherapy as the first-line standard regimen for newly treated FL patients
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For patients with relapsed/refractory FL (R/R FL), treatment options are limited and treatment outcomes are poor
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Professor Li Yuhua said that there is currently no unified standard treatment for FL patients with early disease progression, and R/R FL patients need more effective and less toxic treatment methods
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The GADOLIN study, published in the journal of Clinacal oncology in 2018, evaluated 413 patients with octuzumab combined with bendamustine (GB) in the treatment of rituximab-refractory indolent non-Hodgkin lymphoma (iNHL).
and security
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The results showed that the GB group extended progression-free survival (PFS) in FL patients, reduced the risk of progression or death by 48%, increased the objective response rate (ORR) by 2.
4%, and significantly prolonged the time to next treatment (TTNT) in patients with FL.
)
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The results of the 2019 GALEN study, published in the journal lancet hematology, which evaluated the efficacy of octuzumab combined with lenalidomide in patients with R/R FL, showed a 2-year event-free survival (EFS) rate of 62%.
, the PFS rate was 65%, the 2-year sustained remission rate was 70%, and the OS rate was 87%
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Professor Li Yuhua concluded in this part that the combination of octuzumab and other targeted drugs has significantly improved the survival and remission rate of FL patients.
Ortuzumab will be approved in China in 2021 for the treatment of FL patients.
treatment
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New therapeutic drugs such as CAR-T cell therapy, PI3K inhibitors, bispecific antibody drugs, etc.
, have also carried out corresponding clinical trials in the FL patient population, hoping to bring better treatment to R/R FL patients in the future select
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Chronic lymphocytic leukemia In the 1950s, the treatment of chronic lymphocytic leukemia (CLL) introduced alkylating agents and glucocorticoids.
Now targeted drugs, CAR-T therapy and other drugs have come out one after another, and the treatment of CLL has made rapid progress.

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For the progress of first-line treatment of CLL, most studies have explored whether novel CD20 monoclonal antibody combined with other drugs can achieve deep and durable remission
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The 2019 Lancet Oncology published the results of the iLLUMINATE study, which analyzed the efficacy of octuzumab in combination with ibrutinib (G+ibrutinib) versus octuzumab in combination with chlorambucil (G+Clb).
The results showed that the median PFS in the G+ibrutinib group was longer than that in the G+Clb group, and the 30-month PFS rate, ORR, and undetectable minimal residual disease (uMRD) rates in the G+ibrutinib group were 79% and 88%, respectively.
%, 35%, were significantly higher in the G+Clb group
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The 2021 ASCO Congress announced the results of the CLL 14 study, which analyzed the difference in the efficacy of octuzumab combined with veneclax (G+Ven) and G+chlorambucil (G+Clb) in treatment-naïve patients with CLL , the results showed that the 4-year TTNT rate, OS rate and PFS rate were significantly improved in the G+Ven group, which were 81.
08%, 85.
3% and 74.
0%, respectively
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The CSCO lymphoma diagnosis and treatment guidelines (2021) pointed out that the combination of anti-CD20 monoclonal antibody is still the cornerstone of the treatment of B-cell lymphoma, and the NCCN guidelines (2021 v4) also recommended the combination of otuzumab as the preferred treatment regimen
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Regarding the research progress of patients with relapsed/refractory CLL, the 2020 American Society of Hematology (ASH) announced a study of ortuzumab + ibrutinib + veneclax for treatment-naïve or R/R CLL patients The results showed that the 36-month PFS rate of R/R CLL patients was 95%, the ORR rate was 88%, and the uMRD rate was 44%
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Professor Li Yuhua concluded in this part that the status of CD20 monoclonal antibody in the treatment of CLL is irreplaceable, and a fixed course of combination therapy can achieve a lower level of MRD and reduce the possibility of drug resistance
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As the number of relapses increases, the remission time will be shortened in R/R CLL patients, so new combination regimens need to be explored
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Waldenström macroglobulinemia WM accounts for less than 2% of NHL.
It is a rare mature B-cell indolent NHL.
WM cannot be cured yet.
The current treatment goal is very good partial remission (VGPR)/CR
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Significant progress has also been made in WM therapy
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According to the CSCO lymphoma diagnosis and treatment guidelines (2021), the regimen containing CD20 monoclonal antibody is also the cornerstone of its treatment
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A 2021 study of 48 R/R WM patients receiving octuzumab combined with the PI3K inhibitor idelalisib showed that the median PFS of R/R WM with octuzumab + idelalisib reached 25.
4 month, the 12-month OS rate was 97.
8%, and the 24-month OS rate was 89.
8%
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Professor Li Yuhua concluded in this part that there are still many unmet needs for WM treatment: the CR rate of patients is low, the curative effect is easily affected by mutations, and drug resistance is prone to occur; however, the multi-drug combination regimen has brought new treatment dawn to WM patients
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Mantle cell lymphoma MCL prognosis is closely related to the depth of response to treatment, so it is crucial to improve the CR rate of MCL patients
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For the progress of first-line treatment of newly diagnosed MCL patients, studies have shown that octuzumab + ibrutinib + veneclair, octuzumab + bendamustine + veneclair can respectively make the CR rate reach 86.
6% and 89%
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For the treatment of R/R MCL patients, studies have shown that octuzumab + ibrutinib + veneclax can achieve a CR rate of 67%
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Professor Li Yuhua concluded in this part that the combined use of multiple drugs is the main trend of MCL treatment exploration.
At present, phase III clinical research on CAR-T cell therapy combined with targeted drugs is also underway, which is expected to bring benefits to R/R MCL.
More treatment options
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Summary Professor Li Yuhua finally concluded that in the field of indolent lymphoma treatment, the chemotherapy regimen containing CD20 monoclonal antibody is the cornerstone of treatment, and the multi-target drug combination research carried out on this basis has significantly improved the remission rate and remission of relapsed and refractory patients.
In-depth, such as clinical research of octuzumab + ibrutinib + veneclax for R/R CLL and R/R MCL
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Future clinical trials of CAR-T cell drugs, PI3K inhibitors, and novel CD20 monoclonal antibodies are expected to provide more treatment options for patients with indolent lymphoma
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Professor Li Yuhua, Chief Physician, Doctoral Supervisor, Director of the Department of Hematology, Pearl River Hospital of Southern Medical University, a postdoctoral fellow in the United States Chairman of the Committee Chairman of the Hematology Professional Committee of the Guangdong Women's Physicians Association Chairman of the Human Genetic Resources Management Expert of the Ministry of Science and Technology Outstanding Young Medical Talents in Guangdong Province Biological therapy, he has profound achievements in haploidentical hematopoietic stem cell transplantation, accurate diagnosis of hematological malignancies, molecular targeting and immune cell therapy of malignant tumors, and is good at individuals with refractory and relapsed leukemia, lymphoma, myeloma and other hematological malignancies Chemical immunity and molecular targeted therapy, undertaking more than 20 national, provincial and municipal scientific research projects: 14 patents have been applied for, 10 national invention patents and 1 American invention patent have been authorized; more than 100 papers have been published in domestic and foreign journals, Among them, Nature Nanotechnology, Nature Biomedical Engineering, Pro cNatIAcadSciUSA and other important SCI journals have included more than 50 articles; won 1 second prize of military science and technology progress, 1 third prize of Guangdong science and technology progress, 1 second prize of Guangdong Medical Science and Technology Award, Arizona, USA State University Postdoctoral Research Award 1 Reviewer: Quinta Typesetting: Wenting Execution: Wenting pokes "read the original text", we make progress together