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Follicular lymphoma (FL) is a common type of non-Hodgkin lymphoma (NHL).
8.
1%～23.
5%
.
The incidence rate in China tends to increase year by year, and the age of onset is younger than in foreign countries
.
Although the current treatment methods are constantly updated iteratively, due to the disease characteristics of FL, most patients are still incurable and will eventually face relapse
.
Today, a new generation of anti-CD20 monoclonal antibody-octuzumab has been launched in China.
Will it become a new treatment option for patients with relapsed and refractory FL in the future? In this regard, Yimaitong specially contacted Professor Zhao Yu of the First Medical Center of the Chinese People's Liberation Army General Hospital to discuss the application prospect of otuzumab in a variety of patients with relapsed and refractory indolent lymphoma including FL
.
Prof.
Zhao Yu, Chief Physician and Doctor of Medicine, Department of Hematology, Chinese People's Liberation Army General Hospital, Standing Committee Member, Lymphatic Disease and Lymphoma Oncology Committee, Chinese Medical Education Association Member, Lymphatic and Blood Branch, Chinese Society of Geriatric Oncology Member, Chinese Women Physician Association, Targeted Therapy Committee Second Prize, Beijing Municipal Science and Technology Progress Second Prize, Chinese People's Liberation Army Medical Achievement Third Prize FL's current state of existence? Professor Zhao Yu indeed, the disease characteristics of FL are different from aggressive lymphoma, and most patients are incurable and often face relapse
.
From the current treatment data for FL, the median survival time reported in Europe and the United States is 18 years
.
However, no matter what type of immunochemotherapy is used, patients usually experience disease progression 3 to 5 years after the initial treatment.
The remission rate gradually decreases, the duration of remission and survival time after receiving salvage therapy are significantly shortened, and the toxicity caused by multi-line therapy will gradually increase
.
Figure 1.
Response and survival in patients with relapsed FL.
The PRIMA study showed that 49% of patients who received rituximab combined with chemotherapy and 2 years of rituximab maintenance as standard treatment progressed, relapsed, or died within 10 years.
How to choose an effective treatment plan after relapse of FL patients is one of the problems that need to be solved urgently
.
Yimaitong: What suggestions do you have for the current treatment of relapsed and refractory FL patients, and what new drugs are currently available? Professor Zhao Yu's FL patients have individual differences even if they have relapsed and progressed.
We will consider the next treatment plan based on the clinical situation of the patients
.
Consistent with the evaluation principles for newly treated patients, a comprehensive disease assessment, including routine, laboratory, imaging, and bone marrow examinations, is required for relapsed patients before treatment; at the same time, relapsed patients need to be re-diagnosed and graded by pathology.
The above comprehensive considerations Then, different treatment strategies are formulated for patients, and the specific treatment is mainly based on the latest American NCCN guidelines, Chinese CSCO diagnosis and treatment guidelines and European ESMO guidelines and other evidence-based medical evidence
.
At present, new drugs for relapsed and refractory FL are mainly targeted drugs: (1) Targeting tumor surface antigens: anti-CD20 monoclonal antibodies, bispecific antigens, CD79-targeting antibody-drug conjugates (ADCs) and other tumor cell surface targeted drugs
.
(2) Drugs targeting major intracellular pathways and epigenetic regulation, such as BTK inhibitors, BCL-2 inhibitors, MDM2 inhibitors,
etc.
(3) Target the tumor microenvironment: immune modulators, immune checkpoint inhibitors
.
Although there are many treatment options, anti-CD20 mAb is still the cornerstone of the treatment of relapsed and refractory FL
.
Yi Mai Tong: As you said, anti-CD20 monoclonal antibody is still the cornerstone of treatment for relapsed and refractory FL
.
The new anti-CD20 monoclonal antibody-octuzumab has been on the market for half a year.
What do you think is the prospect of octuzumab in the field of FL treatment? Professor Zhao Yu FL is the most common indolent lymphoma.
As a front-line hematologist, we are very concerned about the progress in the field of relapsed and refractory FL treatment
.
The data from the global phase III GADOLIN study gives us more confidence.
Compared with bendamustine alone, the combination of octuzumab and bendamustine (GB) has a significant effect.
At a median follow-up of 31.
8 months, the GB group was The risk of disease progression was reduced by 43%, the median progression-free survival (PFS) was prolonged to 25.
8 months, and the overall survival (OS) was significantly prolonged (P=0.
0269), providing clinicians and patients with better treatment options
.
Therefore, based on the excellent efficacy of the new anti-CD20 mAb in relapsed and refractory FL, octuzumab can be included in the treatment after comprehensive consideration
.
Figure 2 GADOLIN study: PFS and OS It is worth noting that FL patients who were refractory to rituximab were included in the GADOLIN study, which also reminded us that although octuzumab and rituximab are also anti- CD20 monoclonal antibody, but octuzumab is the world's first humanized, glycosylation-modified type II anti-CD20 monoclonal antibody
.
Unlike type I rituximab, which binds to an antigen-recognition epitope on the CD20 receptor and has a different tumor-killing mechanism, these innovations may also lead to better treatment outcomes for rituximab-refractory FL patients
.
Otuzumab has a unique CD20 antigen-recognition epitope: 170ANPSEKNSP178 region, which only partially overlaps with rituximab's antigen-recognition epitope 168EPANPS173
.
When the core epitope of rituximab (aspartic acid [N] at position 171) is mutated, the affinity of rituximab is greatly reduced, and the CD20 antigen cannot be recognized normally.
.
The core epitope of octuzumab is closer to the C-terminus, so some rituximab-resistant/relapsed patients can still benefit from octuzumab treatment
.
Figure 3 The antigen recognition site of anti-CD20 mAb enhances the direct cell death (DCD) effect of octuzumab due to the altered antigen-binding mode
.
The binding mode of octuzumab is that single-molecule octuzumab binds to two CD20 dimer structures without intermolecular cross-linking, and the octuzumab-CD20 complex does not enter lipid rafts.
This binding mode Can reduce endocytosis of CD20-antibody complexes
.
In addition, due to the different binding mode, octuzumab binds less to C1q, has weaker complement-dependent cytotoxicity (CDC), stronger DCD effect, and activates the intracellular killing signaling pathway
.
Otuzumab is glycoengineered to allow its Fc segment to more efficiently interact with FcγRIII-expressing effector cells, increasing immune effector cell recruitment and promoting activation
.
It has been shown in vitro in human tumor cells that octuzumab induces a 35-fold enhancement of antibody-dependent cell-mediated cytotoxicity and phagocytosis (ADCC/ADCP) compared to rituximab
.
Yi Mai Tong: In the recently concluded ASH meeting, a number of studies on octuzumab were announced.
Could you please comment on the performance of octuzumab in other relapsed or refractory (R/R) indolent lymphomas? to share? Professor Zhao Yu has carried out many explorations in the field of various indolent lymphomas in the past, and this year's ASH report card is also very eye-catching, and announced the chronic lymphocytic leukemia (CLL) in the field of R/R indolent lymphoma.
, progression on mantle cell lymphoma (MCL)
.
R/R CLL: At the recently concluded ASH meeting, a final phase I/II analysis exploring the combination of octuzumab and the SYK inhibitor Entospletinib in patients with R/R CLL showed that in 21 efficacy-evaluable R Among patients with /R CLL, the objective response rate (ORR) was 67% (complete response [CR] rate 14%, partial response [PR] rate 53%), and the bone marrow MRD in all CR patients was negative
.
Although most of the enrolled patients were high-risk patients (n=13), the overall median event-free survival was as high as 27.
5 months, and the ORR of high-risk patients reached 54%.
More data on this program will be released in the future
.
At present, the NCCN guidelines have recommended octuzumab-based regimens for the treatment of naïve and R/R CLL/SLL patients, and octuzumab-based fixed-course regimens are also being explored
.
R/R MCL: MCL is usually incurable due to its biological and clinical heterogeneity.
Novel targeted drugs have become a key means of treating MCL patients.
Or there are inevitable limitations in clinical application
.
A study presented at this year's ASH meeting showed that a fixed-course five-drug combination regimen ViPOR (veneclax, ibrutinib, prednisone, ortuzumab, lenalidomide) was used in the treatment of naïve and R// The safety of R MCL patients is good, no tumor lysis syndrome (TLS) or dose-limiting toxicity (DLT) was detected, and high resistance has been initially shown in patients refractory to CAR-T therapy and BTK inhibitors tumor activity
.
Otuzumab combined with chemotherapy or targeted innovative drugs has been explored a lot, and a considerable number of research results have verified its practical benefits in the field of indolent lymphoma
.
Based on the progress of octuzumab in recent years, octuzumab is expected to become a next-generation cornerstone drug in the field of indolent lymphoma treatment
.
★ Scan the QR code below to enter the "Mystery Exploration" channel ★ Click "Read the original text" to enter the "Mystery Exploration" channel!
8.
1%～23.
5%
.
The incidence rate in China tends to increase year by year, and the age of onset is younger than in foreign countries
.
Although the current treatment methods are constantly updated iteratively, due to the disease characteristics of FL, most patients are still incurable and will eventually face relapse
.
Today, a new generation of anti-CD20 monoclonal antibody-octuzumab has been launched in China.
Will it become a new treatment option for patients with relapsed and refractory FL in the future? In this regard, Yimaitong specially contacted Professor Zhao Yu of the First Medical Center of the Chinese People's Liberation Army General Hospital to discuss the application prospect of otuzumab in a variety of patients with relapsed and refractory indolent lymphoma including FL
.
Prof.
Zhao Yu, Chief Physician and Doctor of Medicine, Department of Hematology, Chinese People's Liberation Army General Hospital, Standing Committee Member, Lymphatic Disease and Lymphoma Oncology Committee, Chinese Medical Education Association Member, Lymphatic and Blood Branch, Chinese Society of Geriatric Oncology Member, Chinese Women Physician Association, Targeted Therapy Committee Second Prize, Beijing Municipal Science and Technology Progress Second Prize, Chinese People's Liberation Army Medical Achievement Third Prize FL's current state of existence? Professor Zhao Yu indeed, the disease characteristics of FL are different from aggressive lymphoma, and most patients are incurable and often face relapse
.
From the current treatment data for FL, the median survival time reported in Europe and the United States is 18 years
.
However, no matter what type of immunochemotherapy is used, patients usually experience disease progression 3 to 5 years after the initial treatment.
The remission rate gradually decreases, the duration of remission and survival time after receiving salvage therapy are significantly shortened, and the toxicity caused by multi-line therapy will gradually increase
.
Figure 1.
Response and survival in patients with relapsed FL.
The PRIMA study showed that 49% of patients who received rituximab combined with chemotherapy and 2 years of rituximab maintenance as standard treatment progressed, relapsed, or died within 10 years.
How to choose an effective treatment plan after relapse of FL patients is one of the problems that need to be solved urgently
.
Yimaitong: What suggestions do you have for the current treatment of relapsed and refractory FL patients, and what new drugs are currently available? Professor Zhao Yu's FL patients have individual differences even if they have relapsed and progressed.
We will consider the next treatment plan based on the clinical situation of the patients
.
Consistent with the evaluation principles for newly treated patients, a comprehensive disease assessment, including routine, laboratory, imaging, and bone marrow examinations, is required for relapsed patients before treatment; at the same time, relapsed patients need to be re-diagnosed and graded by pathology.
The above comprehensive considerations Then, different treatment strategies are formulated for patients, and the specific treatment is mainly based on the latest American NCCN guidelines, Chinese CSCO diagnosis and treatment guidelines and European ESMO guidelines and other evidence-based medical evidence
.
At present, new drugs for relapsed and refractory FL are mainly targeted drugs: (1) Targeting tumor surface antigens: anti-CD20 monoclonal antibodies, bispecific antigens, CD79-targeting antibody-drug conjugates (ADCs) and other tumor cell surface targeted drugs
.
(2) Drugs targeting major intracellular pathways and epigenetic regulation, such as BTK inhibitors, BCL-2 inhibitors, MDM2 inhibitors,
etc.
(3) Target the tumor microenvironment: immune modulators, immune checkpoint inhibitors
.
Although there are many treatment options, anti-CD20 mAb is still the cornerstone of the treatment of relapsed and refractory FL
.
Yi Mai Tong: As you said, anti-CD20 monoclonal antibody is still the cornerstone of treatment for relapsed and refractory FL
.
The new anti-CD20 monoclonal antibody-octuzumab has been on the market for half a year.
What do you think is the prospect of octuzumab in the field of FL treatment? Professor Zhao Yu FL is the most common indolent lymphoma.
As a front-line hematologist, we are very concerned about the progress in the field of relapsed and refractory FL treatment
.
The data from the global phase III GADOLIN study gives us more confidence.
Compared with bendamustine alone, the combination of octuzumab and bendamustine (GB) has a significant effect.
At a median follow-up of 31.
8 months, the GB group was The risk of disease progression was reduced by 43%, the median progression-free survival (PFS) was prolonged to 25.
8 months, and the overall survival (OS) was significantly prolonged (P=0.
0269), providing clinicians and patients with better treatment options
.
Therefore, based on the excellent efficacy of the new anti-CD20 mAb in relapsed and refractory FL, octuzumab can be included in the treatment after comprehensive consideration
.
Figure 2 GADOLIN study: PFS and OS It is worth noting that FL patients who were refractory to rituximab were included in the GADOLIN study, which also reminded us that although octuzumab and rituximab are also anti- CD20 monoclonal antibody, but octuzumab is the world's first humanized, glycosylation-modified type II anti-CD20 monoclonal antibody
.
Unlike type I rituximab, which binds to an antigen-recognition epitope on the CD20 receptor and has a different tumor-killing mechanism, these innovations may also lead to better treatment outcomes for rituximab-refractory FL patients
.
Otuzumab has a unique CD20 antigen-recognition epitope: 170ANPSEKNSP178 region, which only partially overlaps with rituximab's antigen-recognition epitope 168EPANPS173
.
When the core epitope of rituximab (aspartic acid [N] at position 171) is mutated, the affinity of rituximab is greatly reduced, and the CD20 antigen cannot be recognized normally.
.
The core epitope of octuzumab is closer to the C-terminus, so some rituximab-resistant/relapsed patients can still benefit from octuzumab treatment
.
Figure 3 The antigen recognition site of anti-CD20 mAb enhances the direct cell death (DCD) effect of octuzumab due to the altered antigen-binding mode
.
The binding mode of octuzumab is that single-molecule octuzumab binds to two CD20 dimer structures without intermolecular cross-linking, and the octuzumab-CD20 complex does not enter lipid rafts.
This binding mode Can reduce endocytosis of CD20-antibody complexes
.
In addition, due to the different binding mode, octuzumab binds less to C1q, has weaker complement-dependent cytotoxicity (CDC), stronger DCD effect, and activates the intracellular killing signaling pathway
.
Otuzumab is glycoengineered to allow its Fc segment to more efficiently interact with FcγRIII-expressing effector cells, increasing immune effector cell recruitment and promoting activation
.
It has been shown in vitro in human tumor cells that octuzumab induces a 35-fold enhancement of antibody-dependent cell-mediated cytotoxicity and phagocytosis (ADCC/ADCP) compared to rituximab
.
Yi Mai Tong: In the recently concluded ASH meeting, a number of studies on octuzumab were announced.
Could you please comment on the performance of octuzumab in other relapsed or refractory (R/R) indolent lymphomas? to share? Professor Zhao Yu has carried out many explorations in the field of various indolent lymphomas in the past, and this year's ASH report card is also very eye-catching, and announced the chronic lymphocytic leukemia (CLL) in the field of R/R indolent lymphoma.
, progression on mantle cell lymphoma (MCL)
.
R/R CLL: At the recently concluded ASH meeting, a final phase I/II analysis exploring the combination of octuzumab and the SYK inhibitor Entospletinib in patients with R/R CLL showed that in 21 efficacy-evaluable R Among patients with /R CLL, the objective response rate (ORR) was 67% (complete response [CR] rate 14%, partial response [PR] rate 53%), and the bone marrow MRD in all CR patients was negative
.
Although most of the enrolled patients were high-risk patients (n=13), the overall median event-free survival was as high as 27.
5 months, and the ORR of high-risk patients reached 54%.
More data on this program will be released in the future
.
At present, the NCCN guidelines have recommended octuzumab-based regimens for the treatment of naïve and R/R CLL/SLL patients, and octuzumab-based fixed-course regimens are also being explored
.
R/R MCL: MCL is usually incurable due to its biological and clinical heterogeneity.
Novel targeted drugs have become a key means of treating MCL patients.
Or there are inevitable limitations in clinical application
.
A study presented at this year's ASH meeting showed that a fixed-course five-drug combination regimen ViPOR (veneclax, ibrutinib, prednisone, ortuzumab, lenalidomide) was used in the treatment of naïve and R// The safety of R MCL patients is good, no tumor lysis syndrome (TLS) or dose-limiting toxicity (DLT) was detected, and high resistance has been initially shown in patients refractory to CAR-T therapy and BTK inhibitors tumor activity
.
Otuzumab combined with chemotherapy or targeted innovative drugs has been explored a lot, and a considerable number of research results have verified its practical benefits in the field of indolent lymphoma
.
Based on the progress of octuzumab in recent years, octuzumab is expected to become a next-generation cornerstone drug in the field of indolent lymphoma treatment
.
★ Scan the QR code below to enter the "Mystery Exploration" channel ★ Click "Read the original text" to enter the "Mystery Exploration" channel!
