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Introduction Hodgkin lymphoma (HL) is a malignant and proliferative tumor of the lymphatic system.
After standard first-line treatment, most patients can achieve long-term survival
.
In recent years, new progress has been made in the treatment of HL
.
Yimaitong specially invited Professor Li Zhiming from Sun Yat-Sen University Cancer Prevention and Treatment Center for an interview to review the progress of HL treatment in 2021 and discuss the future development direction of HL
.
There are still many difficulties in the treatment of HL.
HL is divided into early and late stages
.
The treatment of early HL patients is mainly chemotherapy combined with radiotherapy, and the cure rate is about 90%
.
The treatment of advanced HL patients is mainly based on ABVD chemotherapy (doxorubicin + bleomycin + vinblastine + dacarbazine), and the long-term survival rate of patients is about 50%
.
Although the cure rate of HL patients is relatively high, the clinical treatment of HL still faces many difficulties
.
For HL patients who received high-intensity chemoradiotherapy in the early stage, once recurrence or progression occurs, it is difficult to achieve better curative effect or continue treatment
.
The long-term survival rate of patients with advanced HL is low, and it is necessary to explore solutions to improve the therapeutic efficacy and long-term survival rate of patients with advanced HL
.
For patients with drug-resistant or relapsed and refractory HL, how to screen at the initial stage of treatment and how to carry out subsequent treatment are also difficult problems
.
In addition, although intensive radiotherapy and chemotherapy can cure HL patients, it will also bring serious toxic and side effects.
How to reduce the toxic and side effects of drugs is also a problem that needs to be considered in clinical treatment
.
In addition, there is still a lack of mature and effective molecular markers for HL treatment to guide treatment, and these issues need to be explored in new clinical studies
.
New breakthroughs and new progress in HL treatment In recent years, some new treatment options have emerged in the field of HL treatment, such as the application of PD-1 inhibitors, velbutuximab (BV) and other drugs in the treatment of HL patients.
Most are in the research stage
.
BV is more mature for HL treatment BV is an antibody-drug conjugate (ADC) targeting CD30.
Its application in HL treatment is relatively mature at present, and it has obtained indications for HL treatment in many countries/regions
.
The ECHELON-1 study, presented at the 2021 EHA meeting, explored BV + AVD (doxorubicin + vinblastine + dacarbazine) combined with chemotherapy in the treatment of untreated stage III/IV classical Hodgkin lymphoma (cHL) The 5-year follow-up results showed that the BV+AVD group had a more significant benefit in progression-free survival (PFS) than the ABVD group (5-year PFS rate: 82.
2% vs 75.
3%; P=0.
002)
.
This study also demonstrated that the BV+AVD regimen can also be used as a recommended treatment regimen for adolescents and young adults with cHL
.
A phase II study presented at the 2021 ICML meeting exploring the efficacy and safety of BV combined with AD (doxorubicin + dacarbazine) in patients with stage I/II cHL showed complete The response (CR) rate was as high as 97%, and the 4-year PFS rate and overall survival (OS) rate were 88% and 100%, respectively, and the safety was controllable
.
Prof.
Li Zhiming said that HL patients can benefit from BV combined chemotherapy regimens, and these combination therapy regimens with better safety and lower toxicity are worthy of further exploration
.
For R/R HL patients, BV also showed better efficacy
.
A study using BV combined with bendamustine as the first salvage regimen for R/R HL patients at the 2021 ICML meeting showed that the objective response rate (ORR) reached 91.
7%, the CR rate reached 75%, and the regimen was safe Good, no patients in the study discontinued treatment due to AEs
.
Similarly, it was announced at the 2021 EHA meeting that BV combined with DHAP regimen (cisplatin, cytarabine, dexamethasone) in the treatment of R/R HL also showed good safety and efficacy.
The 3-year PFS rate reached 77%, and the 3-year OS rate reached 95%
.
Not only that, BV is also suitable for maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT) in R/R HL patients
.
The AMAHRELIS study explored the efficacy of BV maintenance therapy after ASCT in R/R HL patients.
The 2-year PFS rate of R/R HL patients who received BV maintenance therapy reached 75.
3% (95% CI: 68.
4%-84.
3%), and the 2-year OS rate Reaching 96.
4% (95%CI: 94.
2%-100%), R/R HL patients can obtain better survival benefit after ASCT with BV maintenance therapy
.
BV has been approved in China for the treatment of CD30-positive R/R cHL adult patients, and has been included in the recommended drugs of the Chinese Society of Clinical Oncology (CSCO) guidelines
.
In addition, in recent years, BV has gradually been used in the first-line treatment of HL at home and abroad.
The 2021 NCCN guidelines have recommended BV as a first-line treatment drug
.
PD-1 inhibitors are expected to be used in the front-line treatment of HL.
PD-1 inhibitors are also relatively mature drugs in the treatment of HL, and have been included in the NCCN guidelines as a treatment recommendation for relapsed and refractory HL
.
The KEYNOTE-204 study, announced at the 2020 ASCO meeting, compared the efficacy of BV and PD-1 inhibitor pembrolizumab in relapsed and refractory cHL, and the results showed that the pembrolizumab group showed better PFS and ORR (median PFS: 13.
2 months; 12-month PFS rate: 53.
9%; ORR: 65.
6%)
.
Another study explored the efficacy of pembrolizumab combined with BVD regimen in relapsed and refractory cHL.
The results showed that the CR rate of this combination regimen was as high as 95%, and the ORR reached 100%.
This combination regimen can bring depth to cHL.
Mitigation is equally suitable for bridging ASCT
.
Professor Li Zhiming said that through clinical research, PD-1 inhibitors are expected to be used in the front-line treatment of HL patients in the future
.
Future Prospects Professor Zhiming Li said that after 30 years of silence, the treatment of HL has finally achieved a breakthrough in recent years
.
In addition to the world's first antibody-drug conjugated anti-CD30-ADC drug BV, the immune checkpoint inhibitor PD-1 antibody is creating a history of HL treatment
.
At present, small-sample studies on CAR-T targeting CD30 in the treatment of HL have achieved good results, and may become a new research hotspot in HL treatment in the future
.
Professor Li Zhiming, Chief Physician, Doctoral Supervisor, Chairman of the Lymphoma Professional Committee of Guangdong Anti-Cancer Association of Sun Yat-sen University Cancer Center Member of the Standing Committee of the Committee, Secretary General of the Lymphoma Professional Committee of the China Elderly Health Care Association, Standing Committee Member of the Youth Committee of the Lymphoma Professional Committee of the China Anti-Cancer Association Vice Chairman of the Youth Committee of the Chinese Medical Doctor Association Oncologist Branch Deputy Head of the Central Nervous System Lymphoma Group of the Neuro-Oncology Professional Committee Deputy Director of the Targeted and Individualized Therapy Professional Committee of the Guangdong Anti-Cancer Association Deputy Chairman of the Protection Professional Committee Member of the Standing Committee of the Chemotherapy Professional Committee of the Guangdong Anti-Cancer Association Member of the Standing Committee of the Throat Cancer Professional Committee of the Guangdong Provincial Clinical Medicine Association Member of the Nasopharyngeal Cancer Professional Committee of the Guangdong Deep Anti-Cancer Association Deputy Chairman of the Lymphoma Professional Committee of the Guangzhou Anti-Cancer Association Read the original", we make progress together
After standard first-line treatment, most patients can achieve long-term survival
.
In recent years, new progress has been made in the treatment of HL
.
Yimaitong specially invited Professor Li Zhiming from Sun Yat-Sen University Cancer Prevention and Treatment Center for an interview to review the progress of HL treatment in 2021 and discuss the future development direction of HL
.
There are still many difficulties in the treatment of HL.
HL is divided into early and late stages
.
The treatment of early HL patients is mainly chemotherapy combined with radiotherapy, and the cure rate is about 90%
.
The treatment of advanced HL patients is mainly based on ABVD chemotherapy (doxorubicin + bleomycin + vinblastine + dacarbazine), and the long-term survival rate of patients is about 50%
.
Although the cure rate of HL patients is relatively high, the clinical treatment of HL still faces many difficulties
.
For HL patients who received high-intensity chemoradiotherapy in the early stage, once recurrence or progression occurs, it is difficult to achieve better curative effect or continue treatment
.
The long-term survival rate of patients with advanced HL is low, and it is necessary to explore solutions to improve the therapeutic efficacy and long-term survival rate of patients with advanced HL
.
For patients with drug-resistant or relapsed and refractory HL, how to screen at the initial stage of treatment and how to carry out subsequent treatment are also difficult problems
.
In addition, although intensive radiotherapy and chemotherapy can cure HL patients, it will also bring serious toxic and side effects.
How to reduce the toxic and side effects of drugs is also a problem that needs to be considered in clinical treatment
.
In addition, there is still a lack of mature and effective molecular markers for HL treatment to guide treatment, and these issues need to be explored in new clinical studies
.
New breakthroughs and new progress in HL treatment In recent years, some new treatment options have emerged in the field of HL treatment, such as the application of PD-1 inhibitors, velbutuximab (BV) and other drugs in the treatment of HL patients.
Most are in the research stage
.
BV is more mature for HL treatment BV is an antibody-drug conjugate (ADC) targeting CD30.
Its application in HL treatment is relatively mature at present, and it has obtained indications for HL treatment in many countries/regions
.
The ECHELON-1 study, presented at the 2021 EHA meeting, explored BV + AVD (doxorubicin + vinblastine + dacarbazine) combined with chemotherapy in the treatment of untreated stage III/IV classical Hodgkin lymphoma (cHL) The 5-year follow-up results showed that the BV+AVD group had a more significant benefit in progression-free survival (PFS) than the ABVD group (5-year PFS rate: 82.
2% vs 75.
3%; P=0.
002)
.
This study also demonstrated that the BV+AVD regimen can also be used as a recommended treatment regimen for adolescents and young adults with cHL
.
A phase II study presented at the 2021 ICML meeting exploring the efficacy and safety of BV combined with AD (doxorubicin + dacarbazine) in patients with stage I/II cHL showed complete The response (CR) rate was as high as 97%, and the 4-year PFS rate and overall survival (OS) rate were 88% and 100%, respectively, and the safety was controllable
.
Prof.
Li Zhiming said that HL patients can benefit from BV combined chemotherapy regimens, and these combination therapy regimens with better safety and lower toxicity are worthy of further exploration
.
For R/R HL patients, BV also showed better efficacy
.
A study using BV combined with bendamustine as the first salvage regimen for R/R HL patients at the 2021 ICML meeting showed that the objective response rate (ORR) reached 91.
7%, the CR rate reached 75%, and the regimen was safe Good, no patients in the study discontinued treatment due to AEs
.
Similarly, it was announced at the 2021 EHA meeting that BV combined with DHAP regimen (cisplatin, cytarabine, dexamethasone) in the treatment of R/R HL also showed good safety and efficacy.
The 3-year PFS rate reached 77%, and the 3-year OS rate reached 95%
.
Not only that, BV is also suitable for maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT) in R/R HL patients
.
The AMAHRELIS study explored the efficacy of BV maintenance therapy after ASCT in R/R HL patients.
The 2-year PFS rate of R/R HL patients who received BV maintenance therapy reached 75.
3% (95% CI: 68.
4%-84.
3%), and the 2-year OS rate Reaching 96.
4% (95%CI: 94.
2%-100%), R/R HL patients can obtain better survival benefit after ASCT with BV maintenance therapy
.
BV has been approved in China for the treatment of CD30-positive R/R cHL adult patients, and has been included in the recommended drugs of the Chinese Society of Clinical Oncology (CSCO) guidelines
.
In addition, in recent years, BV has gradually been used in the first-line treatment of HL at home and abroad.
The 2021 NCCN guidelines have recommended BV as a first-line treatment drug
.
PD-1 inhibitors are expected to be used in the front-line treatment of HL.
PD-1 inhibitors are also relatively mature drugs in the treatment of HL, and have been included in the NCCN guidelines as a treatment recommendation for relapsed and refractory HL
.
The KEYNOTE-204 study, announced at the 2020 ASCO meeting, compared the efficacy of BV and PD-1 inhibitor pembrolizumab in relapsed and refractory cHL, and the results showed that the pembrolizumab group showed better PFS and ORR (median PFS: 13.
2 months; 12-month PFS rate: 53.
9%; ORR: 65.
6%)
.
Another study explored the efficacy of pembrolizumab combined with BVD regimen in relapsed and refractory cHL.
The results showed that the CR rate of this combination regimen was as high as 95%, and the ORR reached 100%.
This combination regimen can bring depth to cHL.
Mitigation is equally suitable for bridging ASCT
.
Professor Li Zhiming said that through clinical research, PD-1 inhibitors are expected to be used in the front-line treatment of HL patients in the future
.
Future Prospects Professor Zhiming Li said that after 30 years of silence, the treatment of HL has finally achieved a breakthrough in recent years
.
In addition to the world's first antibody-drug conjugated anti-CD30-ADC drug BV, the immune checkpoint inhibitor PD-1 antibody is creating a history of HL treatment
.
At present, small-sample studies on CAR-T targeting CD30 in the treatment of HL have achieved good results, and may become a new research hotspot in HL treatment in the future
.
Professor Li Zhiming, Chief Physician, Doctoral Supervisor, Chairman of the Lymphoma Professional Committee of Guangdong Anti-Cancer Association of Sun Yat-sen University Cancer Center Member of the Standing Committee of the Committee, Secretary General of the Lymphoma Professional Committee of the China Elderly Health Care Association, Standing Committee Member of the Youth Committee of the Lymphoma Professional Committee of the China Anti-Cancer Association Vice Chairman of the Youth Committee of the Chinese Medical Doctor Association Oncologist Branch Deputy Head of the Central Nervous System Lymphoma Group of the Neuro-Oncology Professional Committee Deputy Director of the Targeted and Individualized Therapy Professional Committee of the Guangdong Anti-Cancer Association Deputy Chairman of the Protection Professional Committee Member of the Standing Committee of the Chemotherapy Professional Committee of the Guangdong Anti-Cancer Association Member of the Standing Committee of the Throat Cancer Professional Committee of the Guangdong Provincial Clinical Medicine Association Member of the Nasopharyngeal Cancer Professional Committee of the Guangdong Deep Anti-Cancer Association Deputy Chairman of the Lymphoma Professional Committee of the Guangzhou Anti-Cancer Association Read the original", we make progress together
