Professor Wang Liang: The treatment of Hodgkin's lymphoma is promising in the future!

"The 3rd Jinling Lymphoma Myeloma Youth Forum" brings together experts and scholars in the field of lymphoma and myeloma, based on the current clinical practice of lymphoma and myeloma in China, and conducts in-depth discussions on the latest domestic and foreign achievements and progress in clinical and basic fields
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At the meeting, Professor Wang Liang from Beijing Tongren Hospital Affiliated to Capital Medical University shared "Treatment Progress in Hodgkin’s Lymphoma".
Professor Wang Liang proceeded from prognostic indicators, optimized treatment strategies under the guidance of iPET, and progress in targeted immunotherapy.
After the explanation, the exciting content is as follows
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The prognostic predictor of total tumor volume (TMTV) has been confirmed by studies to affect the prognosis of Hodgkin’s lymphoma (HL).
In the PET risk assessment study, a study by ASCO this year (2021)-baseline TMTV compared to the initial Govern HL for risk stratification
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The study included 392 young advanced HL patients in the AHL2011 study.
Based on the baseline TMTV obtained by baseline FDG-PET, the risk of HL was stratified and the impact on the prognosis was assessed
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Combined with HL patients, the baseline TMTV was divided into high and low groups by cut-off value (350ml), and the 2-year progression-free survival (PFS) rates were 93% and 81%, respectively
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Combining PET2 and baseline TMTV to obtain three risk groups, namely low-risk, medium-risk and high-risk groups, the 2-year PFS rates were 93.
8%, 87.
9%, and 60.
7%, respectively
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Combining baseline TMTV and PET2 status can help clinicians develop more accurate treatment strategies for HL patients
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ctDNA detection is widely used in lymphoma and can run through the whole process of lymphoma diagnosis and treatment
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In the course of HL treatment, ctDNA testing may be used for baseline assessment of patient condition, assessment of treatment effect during treatment, assessment of minimal residual disease after treatment, and follow-up
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A total of 135 patients were included in the IOSI-EMA-003 study.
ctDNA was detected in 90% of the patients, with an average of 27 mutations in each patient
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Overall, the degree of ctDNA load of the mutation is closely related to the size of the tumor
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The high load of ctDNA indicates a poor prognosis, and the combination of IPS may better predict the prognosis of HL
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A study at this year's (2021) EHA meeting also reported similar results.
The study showed that ctDNA is a new tool that can analyze the prognosis of HL and MRD detection
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This study included 324 samples of 121 HL patients.
The results showed that ctDNA conformity before treatment was significantly related to the clinical stage of the patient, and the later the clinical stage, the higher the ctDNA load (P=0.
0001)
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And the ctDNA load before treatment is related to the patient's clinical IPS score.
As the IPS score increases, the ctDNA load also increases (P<0.
0001)
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In addition, the study also found that there are four gene mutations related to mid-term PET assessment, namely IRF8 (P=0.
0324), PIM1 (P=0.
0324), TP53 (P=0.
028) and NOTCH1 (P=0.
0799)
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ctDNA Risk Assessment-Efficacy Prediction Optimized Treatment Strategies Guided by iPET Can patients who are PET-negative in the mid-term be able to abandon radiotherapy? H10 research and RAPID research may inspire us
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After long-term follow-up of the H10 study and RAPID study, it was found that if PET-negative patients give up radiotherapy, their risk of recurrence and metastasis is higher than that of patients receiving radiotherapy.
Most patients relapse two years after treatment, and the recurrence rate of early patients is higher.
There is no significant correlation between the recurrence of advanced patients and whether they receive radiotherapy
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In addition, the study also found that the prognosis of male patients is worse than that of female patients
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These two studies suggest that although the overall prognosis of patients with negative PET in the mid-term is better, for early-stage patients, if radiotherapy is not used for consolidation therapy, it will increase the risk of recurrence
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Radiation therapy may bring late toxicity to patients.
In the CALGB50801 study, the researchers assumed that patients with metaphase PET negative do not need radiotherapy
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The study included 94 patients with stage I/II with large mass cHL, and the primary endpoint was PFS
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The study found that there was no significant difference in PFS between the mid-term PET positive and negative groups.
The estimated 3-year PFS rate was 90% and 93%, and there was no significant difference in overall survival (OS).
The estimated 3-year OS rate was 94%, respectively.
And 99%
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This study is the first prospective study of early large lump cHL patients.
In the study, 78% of patients avoided the possible toxicity caused by the use of radiotherapy
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Another study analyzed whether the replacement of procarbazine in esc BEACOPP with dacarbazine in advanced HL can reduce toxicity
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The study retrospectively analyzed 205 patients with first-line advanced HL, of which 147 patients received esc BEACOPP treatment
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At a median follow-up of 22.
9 months, 2 patients in the esc BEACOPP group died, 1 patient was refractory to primary treatment, and 3 patients progressed
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2 patients in the control group progressed (1 died after progressing)
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There was no significant difference between the two groups in retrospective analysis of PFS
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In addition, the phase 3 ECHELON-1 study (NCT01712490) 5-year follow-up data update showed that, compared with the ABVD regimen, the first-line phase III/IV cHL received vebutuximab combined with AVD (A+AVD) regimen, and 5-year PFS Significantly extended
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ECHELON-1 study (NCT01712490) 5-year follow-up data targeted immunotherapy Progressive programmed cell death (PD-1) pathway is an important part of the occurrence and immune escape of cHL
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The unique immune microenvironment of HL enables PD-1/L1 inhibitors to perform better
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The CheckMate 205 study evaluated the efficacy and safety of nivolumab for R/R cHL patients who failed ASCT
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With a median follow-up of 18 months, 40% of the patients continued to receive treatment, the overall objective response rate (ORR) was 69%, the overall median response time was 16.
6 months, and the median PFS was 14.
7 months
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However, after long-term follow-up, it was found that the 2-year PFS rate was 37%, but the 5-year PFS rate was only 18%.
Therefore, although the 5-year OS rate reached 71.
5%, from the perspective of PFS, the PD-1 inhibitor single agent The efficacy of treating R/R cHL patients is still limited
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Patients who discontinued the drug in the study also experienced different degrees of disease progression in the follow-up
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Regarding the discontinuation of R/R HL after the application of PD-1 inhibitors
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A study published in Haematologica showed that the main reason for patients discontinuing drugs after using PD-1 inhibitors is to achieve complete remission (CR), with a remission rate of 85.
7%, but there are also 28.
6% of patients due to drug toxicity.
Discontinue the drug
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The median time from discontinuation of PD-1 inhibitors to relapse was 12.
1 months, and the longest patient stopped taking about 2 years
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After stopping the drug and recurring, using PD-1 inhibitors again, 57.
1% of patients still achieved CR
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That is to say, the use of PD-1 inhibitors again after the patient relapses is also a treatment strategy
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Which patients can "successfully" stop taking PD-1 inhibitors? Professor Wang Liang introduced that young patients are more likely to successfully stop the drug, and patients who use PD-1 inhibitors to achieve deeper remission in the early stage are more likely to successfully stop the drug
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In the early high-risk cHL, the cure rate is higher with conventional treatment, but the acute and chronic toxic reactions are severe
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The NIVAHL study evaluated the efficacy of two combination regimens of AVD and nivolumab in the treatment of high-risk cHL
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The study was divided into two groups, a synchronous group: 55 patients were enrolled, and they received nivolumab combined with AVD (N-AVD) treatment on the 1st and 15th days.
A total of 4 cycles, 28 days as a cycle
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After the end of systemic treatment, local radiotherapy of 30 Gy was given to consolidate
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Sequential group: 54 cases were enrolled and received 4 cycles of nivolumab monotherapy, followed by two cycles of N-AVD and two cycles of AVD.
After systemic treatment, they received 30 Gy of local radiotherapy for consolidation
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In the middle stage after 2 cycles of N-AVD in the synchronous group and 4 cycles of nivolumab monotherapy in the sequential group, 54 patients (100%) and 49 patients (96%) received objective responses, respectively.
47 cases (87%) in the group and 26 cases (51%) in the sequential group received CR
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The median follow-up time was 13 months.
The 12-month progression-free survival rate of patients receiving concurrent treatment was 100%, and that of patients receiving sequential treatment was 98% (95% CI, 95%-100%)
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The NIVAHL study shows that the two combination regimens of simultaneous or sequential nivolumab and AVD are feasible and both have a higher remission rate
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The PFS of up to 12 months and the extremely high CR rate after 4 cycles of nivolumab monotherapy reflect that the first-line treatment of cHL based on anti-PD-1 therapy is worthy of further evaluation in future trials
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In addition, in the study of nivolumab + BV first-line treatment of elderly patients, an ORR of 61% and a CR rate of 48% were achieved, which brings new options to elderly patients
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PD-1 monoclonal antibody versus CD30 monoclonal antibody in the treatment of R/R HL, which is better? The results of the KEYNOTE204 study show that PD-1 inhibitors have significant benefits compared with CD30 monoclonal antibody PFS
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KEYNOTE-204 was enrolled in R/R HL patients who relapsed after autologous transplantation or were refractory to autologous transplantation or were not suitable for autologous transplantation
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The results showed that the median PFS of the pembrolizumab group and the BV group were 13.
2 months and 8.
3 months, respectively.
Pembrolizumab significantly improved the patients' PFS compared with BV
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In terms of remission rate, the overall ORR of the pembrolizumab group was 65.
6%, which was significantly higher than that of the BV group (54.
2%, P=0.
023).
The complete remission rate of the two groups was similar (25% vs 24%)
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The latest analysis shows that PD-1 inhibitors improve the quality of life of patients more significantly
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This study provides a new standard treatment for R/R HL who relapsed after autologous transplantation or cannot tolerate autologous transplantation
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In addition, the BGB-A317-203 study of tislelizumab in the treatment of R/R cHL showed that R/R cHL patients who received tislelizumab monotherapy had an ORR of 87.
1% and a CR rate of 67.
1%.
Subgroup analysis showed that among 13 patients who had previously received ASCT, 11 achieved CR, showing the therapeutic advantage of PD-1 inhibitors
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BGB-A317-203 study subgroup analysis In the end-line treatment, the new antibody conjugated drug camidanlumab targeting CD25 is used to treat patients with relapsed/refractory Hodgkin's and non-Hodgkin's lymphoma Phase 1 clinical trial results The results of the test showed that among the R/R cHL patients treated with camidanlumab, the ORR reached 86.
5%
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After the phase 2 study expanded the sample size, its ORR was able to reach 83%, and the drug was well tolerated.
This drug brings a new choice to patients with R/R cHL
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There are still many problems to be solved in the current treatment of R/R cHL patients
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For example, how to optimize on the basis of ensuring the efficacy, and for the treatment of R/R cHL patients, how to integrate some existing new drugs with the original treatment plan in the new drug era, and how to combine PD-1 inhibitors with targeted drugs, etc.
Etc.
, these are the current and future research directions
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Professor Wang Liang, Chief Physician of the Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing Tongren Hospital, is an academic leader (in charge of department work) and graduated from Peking Union Medical College.
"Tongren Hospital Young Outstanding Talents" program won the "Honoring Life·2017 Glory Doctor-Youth Innovation Award" Member of the 11th Youth Committee of the Hematology Branch of the Chinese Medical Association Standing Committee Member of the Myeloma Professional Committee of the Chinese Medical Education Association Specializing in lymphoma and other hematological malignancies Tumor diagnosis and treatment presided over a number of topics such as the National Natural Science Foundation, published dozens of SCI papers "read the original text", we make progress together