2021 CSCO Professor Li Zhiming: Progress in the treatment of Hodgkin’s lymphoma

The 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference will be held on September 25-29, 2021.
The theme of this conference is "Focus on Innovative Research, Leading the Original Future"
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The conference continues to adhere to the fundamental purpose of CSCO, adopts new forms to actively carry out academic exchange activities in special periods, promotes academic exchanges and scientific and technological cooperation in the field of clinical oncology in China, encourages support for clinical research and innovation, and advocates multidisciplinary standardized comprehensive treatment based on Precision oncology actively promotes the development of the discipline
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At this CSCO conference, Professor Li Zhiming from Sun Yat-sen University Cancer Center gave a report on the topic of "Treatment Progress in Hodgkin's Lymphoma (HL)".
Yimaitong organized the main contents as follows
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The treatment progress of newly-treated Hodgkin’s lymphoma Professor Li Zhiming first introduced the research progress of newly-treated HL
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The results of the ALLICANCE study were announced at the ICML conference this year.
The study explored PET-CT-guided treatment strategies (2 courses of ABVD regimen followed by PET-CT evaluation, positive patients received 4 cycles of enhanced BEACOPP regimen and involved field radiotherapy [ IFRT], negative patients continue to receive 4 cycles of ABVD treatment) in stage I/II classic Hodgkin’s lymphoma (cHL)
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The results of the study show that PET-CT-guided treatment strategies can bring progress-free survival (PFS) benefits for cHL patients.
78% of patients do not need to receive radiotherapy or enhanced BEACOPP treatment.
Interim PET-CT assessment is useful for cHL treatment.
Important guidance value
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 The ICML conference also announced the results of the EORTC/FIL/LYSA H10 study and the UK NCRI RAPID study.
The two studies evaluated the necessity of radiotherapy for newly-treated patients with limited-stage cHL who had a negative PET-CT test to receive ABVD treatment
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The results of the study showed that the omission of radiotherapy in patients with limited-stage HL who had a negative PET-CT test after treatment with the ABVD regimen could lead to an increase in the probability of early (<2 years) recurrence
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For early cHL patients after ABVD treatment, radiotherapy is still necessary
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 A study published at the EHA conference this year explored the efficacy and safety of enhanced BEACOPDac regimen (replacement of procarbazine in the enhanced BEACOPP regimen with dacarbazine) in patients with advanced HL
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The results of the study showed that compared with the enhanced BEACOPP regimen, the enhanced BEACOPDac regimen was similar in efficacy, and there was no significant difference in PFS in HL patients after receiving the two regimens
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At the same time, enhancing the safety of BEACOPDac has more advantages, the number of elective days of patients' hospitalization is lower (3.
74 vs 5.
83; P=0.
118), and the red blood cell transfusion received is significantly less (1.
93 units vs 4.
16 units; P<0.
001)
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 In addition to the research progress of the above-mentioned chemotherapy regimens, targeted therapy drugs have also made progress in HL in recent years
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This year’s EHA conference announced the 5-year follow-up results of the ECHELON-1 study exploring the combination of verbutuximab (BV) and chemotherapy in the treatment of newly treated stage III/IV cHL
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At a median follow-up of 60.
9 months, the PFS benefit of the BV+AVD group was more significant than that of the ABVD group (5-year PFS rate: 82.
2% vs 75.
3%; P=0.
002)
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At the same time, 85% of patients with peripheral neuropathy (PN) symptoms were completely relieved or improved after BV+AVD treatment
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BV combined with chemotherapy can achieve long-lasting PFS benefits for newly treated cHL patients, while the safety is controllable
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 The subgroup analysis of the study explored the efficacy and safety of the BV+AVD regimen in adolescents and young adults with cHL
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The results of the study showed that the BV+AVD regimen also brought PFS benefits in cHL patients <30 years old and <40 years old (5-year PFS rate of patients <30 years old: 87.
1% vs 79.
9%; 5-year PFS rate of patients <40 years old: 86.
3% vs 79.
4%)
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The safety of the BV+AVD regimen in cHL patients less than 30 years old and less than 40 years old was equally good, with 88% and 89% of patients with PN symptoms relieved or improved, respectively
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For adolescents and young adults with cHL, the BV+AVD regimen can also be used as a recommended treatment regimen
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 Another phase I/II study explored the efficacy and safety of the BV+AVD regimen in the treatment of newly treated children with advanced cHL
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The results of the study showed that the overall response rate (ORR) of the BV+AVD regimen in late childhood cHL reached 81%, and the complete response (CR) rate reached 76%, while the safety was controllable
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This program has a significant efficacy in advanced cHL in children, which is consistent with the efficacy and safety of adult patients observed in the ECHELON-1 study
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 A phase II study announced at the ICML conference this year explored the efficacy and safety of BV combined with AD in patients with stage I/II cHL
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The results of the study showed that the CR rate of the combined regimen was as high as 97%, the 4-year PFS rate and overall survival (OS) rate were 88% and 100%, respectively, and there was no difference in CR rate and PFS between patients with good early prognosis and patients with poor prognosis, and it was safe at the same time Controllable
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Professor Li Zhiming said that under the condition that cHL patients generally obtain better curative effects, a combination therapy with better safety and lower toxicity is worthy of further exploration
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 A phase II study conducted by the German Hodgkin’s Lymphoma Research Group (GHSG) explored two enhanced BEACOPP-based regimens combined with BV (BrECADD regimen: BV, etoposide, doxorubicin, cyclophosphamide, Dacarbazine, dexamethasone; BrECAPP program: BV, etoposide, doxorubicin, cyclophosphamide, procarbazine, prednisone) for the efficacy and safety of patients with newly diagnosed advanced cHL
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The results of the study showed that at a median follow-up of 34 months, the 3-year PFS rates of BrECADD and BrECAPP were 89.
7% and 90.
2%, respectively, and the 3-year OS rates were 95.
4% and 100%, respectively
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The two treatments have definite efficacy and controllable safety in newly-treated patients with advanced cHL, and can be used as alternatives to enhance BEACOPP
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 In addition to the use of first-line therapy, the use of BV in consolidation therapy is also worthy of attention
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The Phase II BRAPP2 study announced at the ICML conference explored the efficacy and safety of BV as a first-line consolidation therapy for patients with cHL with positive mid-term PET-CT detection after radiotherapy and chemotherapy
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The results of the study showed that the CR rate of cHL patients after BV consolidation treatment reached 87.
2%, and the 2-year PFS rate reached 90%
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However, BV consolidation therapy also led to more adverse events (AE), 29.
3% of patients had PN ≥2, and 2 patients were discontinued treatment
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For high-risk cHL patients, BV can be used for consolidation therapy on the basis of radiotherapy and chemotherapy
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The progress of the treatment of relapsed and refractory Hodgkin's lymphoma Professor Li Zhiming then introduced the research progress of relapsed and refractory (R/R) HL
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The second-line rescue treatment of R/R HL is commonly used with platinum-based chemotherapy regimens, and ORR can reach 60%-80%, but the CR rate of these regimens is relatively low (<50%)
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There is still a need to explore better second-line rescue treatment options to improve the prognosis of patients with R/R HL
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 For R/R HL patients, BV is also a better therapeutic drug
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Relevant studies have shown that the ORR of BV monotherapy for R/R HL reached 75%, but the CR rate was only 34%, and the duration of remission was relatively short
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The chemotherapy regimen of BV combined with other drugs is more effective in R/R HL.
Donostia University Hospital in Spain has carried out a study to explore BV combined with bendamustine as the first rescue treatment for R/R HL patients.
Efficacy and safety
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The research results announced at the ICML conference this year showed that the ORR of the BV combined with bendamustine regimen reached 91.
7% and the CR rate reached 75%
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The program is safe, and no patients in the study discontinued treatment due to AEs
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For R/R HL patients, the combined BV regimen is a better second-line rescue treatment option
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 This year’s EHA conference announced the long-term follow-up results of the BV combined with DHAP regimen for the treatment of R/R HL.
The results of the study showed that the 3-year PFS rate of the BV-DHAP regimen reached 77%, and the 3-year OS rate reached 95%
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In addition, the study found that serum soluble thymus activation regulatory chemokine (sTARC) can be used as an early prognostic marker for the treatment of R/R HL with BV-DHAP regimen.
Patients who have achieved disease remission will have a decline in sTARC level after 1 cycle of BV-DHAP treatment.
More significant (P=0.
027)
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 The AETHERA study explored the necessity of maintenance therapy for BV in patients with R/R HL after ASCT
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At a median follow-up of 30 months in the study, patients receiving BV maintenance treatment had a higher 2-year PFS rate (63% vs 51%; HR: 0.
57; P=0.
0013)
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The AMAHRELIS study further explored the necessity of BV maintenance treatment in patients with R/R HL after ASCT in the real world
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The results of the study showed that the 2-year PFS rate of R/R HL patients receiving BV maintenance treatment reached 75.
3% (95%CI: 68.
4%-84.
3%), and the 2-year OS rate reached 96.
4% (95%CI: 94.
2%-100%)
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BV maintenance treatment after ASCT can effectively improve the survival benefit of R/RHL patients, and at the same time, achieving complete molecular remission (CMR) after rescue treatment is significantly related to the improvement of OS (P=0.
0018)
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 The elderly patients with R/R HL cannot tolerate high-intensity chemotherapy due to their poor basic conditions.
These patients also have unmet need for treatment
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Immunotherapy may bring new treatment options for these patients
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The Keynote-204 study compared the efficacy of PD-1 monoclonal antibody pembrolizumab and BV in the second-line treatment of R/R HL patients
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The results of the study showed that compared with BV, pembrolizumab was superior to PFS in patients with R/R HL (median PFS: 13.
2 months vs 8.
3 months; 12-month PFS rate: 53.
9% vs 35.
6%), Pa The ORR of bolizumab for R/R HL was also higher (65.
6% vs 54.
2%)
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The CheckMate812 study compared the efficacy of BV single-agent and BV combined with PD-1 monoclonal antibody nivolumab regimen in R/R HL.
The study is currently still in progress, and we look forward to the publication of future research results to further verify PD-1 The efficacy of monoclonal antibodies in the second-line rescue treatment of R/R HL
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 In addition to PD-1 monoclonal antibody, some new drugs also show considerable therapeutic prospects in R/R HL
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A phase II study explored the efficacy of the antibody-drug conjugate Camidanlumab tesirine (Cami) in R/R cHL
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The research results announced at the ICML conference this year showed that the ORR of Cami treatment of R/R cHL reached 66.
3%, the CR rate reached 27.
7%, the median PFS reached 9.
2 months, and the median duration of remission (DOR) was not reached
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For R/R cHL patients who have failed treatment with BV and PD-1 inhibitors, Cami provides a better treatment option
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 The prospect of using chimeric antigen receptor T cell (CAR-T) immunotherapy in R/R HL is also worthy of attention
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The results of a phase I/II study showed that the ORR of CD30 CAR-T treatment for R/R HL reached 62%, and the CR rate reached 51%.
Among the patients who achieved CR, the DOR of 5 patients was more than 1 year
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At the same time, CD30 CAR-T has good safety in R/RHL.
The cytokine release syndrome (CRS) in the study is all grade 1, and there is no dose-limiting toxicity and neurotoxicity.

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Summary Professor Li Zhiming finally concluded: How to improve the effectiveness of the treatment plan and control the toxicity is a difficult problem facing the current HL treatment
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It is necessary to further explore the pathogenesis of HL and find more biomarkers to guide the treatment of HL
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The treatment of elderly HL patients is still facing challenges, and more clinical studies are needed to provide better treatment options
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At the same time, we look forward to more research advances in HL treatment in the future to guide the clinical practice of HL
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Professor Li Zhiming, Chief Physician, Doctoral Supervisor, Director of the Lymphoma Professional Committee of Guangdong Anti-Cancer Association of Sun Yat-sen University Cancer Center Committee Standing Committee Secretary-General of the Lymphoma Professional Committee of the Chinese Geriatric Healthcare Association, Standing Committee Member, Deputy Chairman of the Youth Committee of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association Deputy Chairman of the Youth Committee of the Oncologist Branch of the Chinese Medical Doctor Association Vice Chairman of the Standing Committee of the Lymphoma Branch of the Chinese Medical Education Association Chinese Anti-Cancer Association Deputy Director of the Central Nervous System Lymphoma Group of the Neuro-Oncology Professional Committee Deputy Chairman of the Targeted and Individualized Therapy Professional Committee of Guangdong Anti-Cancer Association Deputy Chairman of the Tumor Immunity Professional Committee of Guangdong Society of Integrative Medicine and Guangdong Provincial Health Management Society Fertility 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 Pharyngeal Tumor Professional Committee of the Guangdong Provincial Society of Clinical Medicine Member of the Nasopharyngeal Cancer Professional Committee of the Guangdong Deep Anti-Cancer Association Member of the Lymphoma Professional Committee of the Guangzhou Anti-Cancer Association Read the original ", we make progress together