The 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference were held on September 25-29, 2021, with the theme of "Focusing on Innovative Research and Leading the Original Future". The conference continues to uphold the fundamental purpose of CSCO, actively carries out academic exchange activities in new forms in special periods, promotes academic exchanges and scientific and technological cooperation in the field of clinical oncology in China, encourages and supports clinical research and innovation, advocates precision oncology on the basis of multidisciplinary standardized comprehensive treatment, and actively promotes the development of disciplines. At the CSCO conference, Professor Li Zhiming of the Cancer Prevention and Control Center of Sun Yat-sen University gave a report on the theme of "Treatment Progress of Hodgkin Lymphoma (HL)", and the main contents of the medical pulse were sorted out as follows.
Progress in the treatment of initial Hodgkin lymphoma
Professor Li Zhiming first introduced the research progress of Chuzhi HL. The results of the ALBUMANCE study, which were presented at this year's ICML conference, explored the efficacy of PET-CT-guided treatment strategies (PET-CT evaluation after 2 courses of ABVD regimen, 4 cycles of enhanced BEACOPP regimen and affected wild radiotherapy [IFRT] in positive patients, and 4 cycles of ABVD regimen for negative patients) in stage I/II classical Hodgkin lymphoma (cHL). The results show that PET-CT-guided treatment strategies can benefit progression-free survival (PFS) in patients with cHL, 78% of patients do not need to receive radiotherapy or enhanced BEACOPP regimens, and mid-term PET-CT evaluation has important guiding value for cHL treatment.
The results of the EORTC/FIL/LYSA H10 study and the UK NCRI RAPID study were also presented at the ICML conference, which assessed the need for radiotherapy after treatment with abVD regimen in patients with initial limited-term cHL who tested negative for PET-CT. The results of the study showed that the omission of radiotherapy in patients with a limited-time HL who tested negative pet-CT after TREATMENT with the ABVD regimen led to an increased probability of recurrence in the early (<2 years). For patients with early cHL after ABVD regimen, radiation therapy is still necessary.
A study presented at this year's EHA conference explored the efficacy and safety of the enhanced BEACOPDac regimen (replacing methyl benzylhydrazine with dacarbazine in the enhanced BEACOPP regimen) in patients with advanced HL. The results of the study showed that the enhanced BEACOPDac regimen was similar in efficacy compared with the enhanced BEACOPP regimen, and there was no significant difference in PFS after receiving the two regimens in HL patients. Enhancing the safety of BEACOPDac was also advantageous, with patients having fewer selective days of hospitalization (3.74 vs 5.83; P=0.118) and receiving significantly fewer erythrocyte transfusions (1.93 units vs 4.16 units; P<0.001).
In addition to the research progress of the above chemotherapy regimens, targeted therapy drugs have also made some progress in HL in recent years. The results of a five-year follow-up study exploring vibutuximab (BV) in combination with chemotherapy for the treatment of phase III/IV cHL were presented at this year's EHA conference. At a median follow-up of 60.9 months, the PFS benefit was more significant in the BV+AVD group (5-year PFS rate: 82.2% vs 75.3% ;P=0.002). At the same time, 85% of patients with peripheral neuropathy (PN) symptoms completely alleviated or improved after treatment with the BV +AVD regimen. BV plus chemotherapy regimens can benefit from long-lasting PFS in patients treating cHL with controllable safety.
Subgroup analysis of the study explored the efficacy and safety of BV+AVD regimens in adolescents and young adults with cHL. The results showed that the BV+AVD regimen also benefited from PFS in patients aged <30 years and < 40 years of cHL (5-year PFS rate: 87.1% vs 79.9% in < 30-year patients and 5-year PFS rate at < 40 years of age: 86.3% vs 79.4%). The BV+AVD regimen was equally safe in <30 years of age and < 40 years of age in patients with cHL, with PN symptoms relieved or improved in 88% and 89% of patients, respectively. For adolescent and young adult cHL patients, BV+AVD regimens are also recommended.
Another Phase I/II study explored the efficacy and safety of the BV+AVD regimen in treating patients with early childhood with advanced cHL. The results of the study showed that the total 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. This regimen has a significant efficacy in late childhood cHL, consistent with the efficacy and safety of adult patients observed in the ECCLON-1 study.
A Phase II study presented at this year's ICML conference explored the efficacy and safety of BV combined AD regimens in patients with phase I/II cHL. The results of the study showed that the CR rate of the combined protocol was as high as 97%, the 4-year PFS rate and the overall survival (OS) rate were 88% and 100%, respectively, and there was no difference between the CR rate and PFS in patients with a good early prognosis and the patient with poor prognosis, and the safety was controllable. Professor Li Zhiming said that in the case of cHL patients generally obtaining better efficacy, the combination treatment plan with better safety and lower toxicity deserves further exploration.
A Phase II study conducted by the Hodgkin Lymphoma Research Group (GHSG) in Germany explored the efficacy and safety of two enhanced BEACOPP-based regimens combined with BV (BrECADD regimens: BV, etoposide, doxorubicin, cyclophosphamide, dacarbazine, dexamethasone; BrECAPP regimens: BV, etoposide, doxorubicin, cyclophosphamide, methyl benzylhydrazine, prednisone) in the treatment of patients with early stages of cHL. The results showed that at the median follow-up of 34 months, the 3-year PFS rates of the BrECADD protocol and the BrECAPP protocol were 89.7% and 90.2%, respectively, and the 3-year OS rate was 95.4% and 100%, respectively. Both regimens are effective and manageable in patients with advanced cHL at the beginning of treatment, and can be used as an alternative to enhancing the BEACOPP regimen.
In addition to first-line therapy use, the use of BV in consolidation therapy is also worthy of attention. The Phase II BRAPP2 study presented at the ICML conference explored the efficacy and safety of BV as a consolidation therapy drug after first-line chemoradiotherapy in patients with positive ctHL tests in mid-term PET-CT. The results of the study showed that the CR rate of cHL patients after BV consolidation therapy reached 87.2%, and the 2-year PFS rate reached 90%. However, BV consolidation therapy also led to more adverse events (AE), with 29.3% of patients developing ≥ grade 2 PN and leading to termination of treatment in 2 patients. For high-risk cHL patients, consolidation therapy with BV can be tried on the basis of chemoradiation.
Progression in the treatment of relapsed refractory Hodgkin lymphoma
Professor Li Zhiming then introduced the research progress of relapsing refractory (R/R) HL. Second-line salvage therapy for R/RHL is commonly used in platinum-containing chemotherapy regimens, with ORR of 60% to 80%, but the CR rate of these regimens is relatively low (<50%). There is still a need to explore better second-line salvage regimens to improve outcomes for patients with R/RHL.
For patients with R/RHL, BV is also a better treatment. Related studies have shown that the ORR of BV monotherapy R/R HL reaches 75%, but the CR rate is only 34%, and the duration of remission is relatively short. Chemotherapy regimens with BV plus other drugs are more effective in R/RHL, and a study was conducted at the University Hospital of Donostia in Spain to explore the efficacy and safety of BV combined with bendamastine as the first salvage regimen for patients with R/RHL. The results of the study presented at this year's ICML conference showed that the ORR of the BV combined bendamustine protocol reached 91.7%, and the CR rate reached 75%. The protocol was safe and no patients in the study stopped treatment because of AE. For patients with R/RHL, the combination regimen of BV is a better second-line salvage option.
The results of long-term follow-up of R/RHL in the treatment of R/RHL with BV-DHAP regimen were published at this year's EHA conference, and the results showed that the 3-year PFS rate of the BV-DHAP regimen reached 77% and the 3-year OS rate reached 95%. In addition, serum soluble thymus activation modulating chemokines (sTARC) were found to be a marker for early prognosis of R/RHL in the BV-DHAP regimen, and the decline in sTARC levels after 1 cycle of BV-DHAP therapy in patients who achieved disease remission was more significant (P=0.027).
The AETHERA study explored the need for BV maintenance therapy after ASCT in patients with R/RHL. At 30 months of follow-up, patients receiving maintenance BV had a higher 2-year PFS rate (63% vs 51%; HR: 0.57; P=0.0013). The AMAHRELIS study further explores the need for maintenance therapy for BV after ASCT in real-world patients with R/RHL. The results of the study showed that the 2-year PFS rate of R/R HL patients receiving BV maintenance therapy reached 75.3% (95% CI: 68.4% to 84.3%), and the 2-year OS rate reached 96.4% (95% CI: 94.2% to 100%). Post-ASCT BV maintenance therapy was effective in improving survival benefit in patients with R/RHL, while salvage treatment to a complete molecular response (CMR) was significantly associated with OS improvement (P=0.0018).
Elderly patients with R/RHL are unable to tolerate high-intensity chemotherapy due to poor underlying conditions, and there is an unmet need for treatment in this part of the patient. Immunotherapy may open up new treatment options for this subset of patients. The Keynote-204 study compared the efficacy of PD-1 monoclonal parbolizumab with BV second-line treatment of patients with R/RHL. The results showed that patients with Paborizumab in R/RHL had better PFS (median PFS: 13.2 months vs 8.3 months; 12-month PFS rate: 53.9% vs 35.6%), and the ORR of perbolizumab in the treatment of R/R HL was also higher (65.6% vs 54.2%). The CheckMate812 study compared the efficacy of BV monotherapy and BV combined with PD-1 monoclonal antibody navuliyumab regimen in R/RHL, and the study is still ongoing, and it is expected that the publication of future studies will further verify the efficacy of PD-1 monoclonal antibody in second-line rescue therapy for R/R HL.
In addition to PD-1 monoclonal antibodies, some new drugs also show considerable therapeutic prospects in R/RHL. A Phase II study explored the efficacy of the antibody drug conjugate Camidanlumab tesirine (Cami) in R/R cHL. The results of the study released at this year's ICML conference showed that the ORR of Cami for 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. For patients with R/R cHL who have failed treatment with BV and PD-1 inhibitors, Cami offers a better treatment option.
The prospect of chimeric antigen receptor T cell (CAR-T) immunotherapy in R/RHL is also worthy of attention. The results of a phase I/II study showed that the ORR of CD30 CAR-T for R/R HL reached 62%, the CR rate reached 51%, and 5 patients who achieved CR had DOR for more than 1 year. At the same time, CD30 CAR-T is safe in R/RHL, and the cytokine release syndrome (CRS) that appeared in the study was all grade 1, and there was no dose-limiting toxicity or neurologic toxicity.
summary
Professor Li Zhiming finally concluded: How to improve the effectiveness of the treatment plan and control toxicity is the current problem facing HL treatment. The pathogenesis of HL needs to be further explored and more biomarkers need to be sought to guide the treatment of HL. The treatment of elderly patients with HL is still challenging, and more clinical studies are needed to provide better treatment options. At the same time, it is expected that more research progress in HL treatment will appear in the future to guide the clinical practice of HL.
Professor Li Zhiming
Professor, Chief Physician, Doctoral Supervisor, Cancer Prevention and Control Center of Sun Yat-sen University
Chairman of the Lymphoma Professional Committee of Guangdong Anti-Cancer Association
Deputy Secretary-General and Standing Committee Member of the Anti-Lymphoma Alliance of the Chinese Society of Clinical Oncology (CSCO).
Member of the Standing Committee of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association
Secretary-General and Standing Committee Member of the Lymphoma Professional Committee of the China Geriatric Health Care Association
Vice Chairman of the Youth Committee of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association
Vice Chairman of the Youth Committee of the Oncologist Branch of the Chinese Medical Doctor Association
Member of the Standing Committee of the Lymphoma Branch of the Chinese Medical Education Association
Deputy Leader of the Central Nervous System Lymphoma Group of the Neuro-Oncology Professional Committee of the Chinese Anti-Cancer Association
Vice Chairman of the Targeted and Individualized Therapy Professional Committee of Guangdong Anti-Cancer Association
Vice Chairman of tumor immunology professional committee of Guangdong Association of Integrative Traditional and Western Medicine
Vice Chairman of fertility protection professional committee of Guangdong Health Management Society
Member of the Standing Committee of the Chemotherapy Professional Committee of Guangdong Anti-Cancer Association
Member of the Standing Committee of the Throat Tumor Professional Committee of the Guangdong Clinical Medical Association
Member of the Nasopharyngeal Cancer Professional Committee of Guangdong Shenzhen Anti-Cancer Association
Vice Chairman of the Lymphoma Professional Committee of Guangzhou Anti-Cancer Association