2021 CSCO Professor Bai Ou: Prognostic Exploration and Treatment Optimization of DLBCL

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 conference, Professor Bai Ou from Bethune First Hospital of Jilin University gave a theme report on "Diffuse Large B-Cell Lymphoma (DLBCL) Prognosis Exploration and Treatment Optimization".
Yimaitong organized the main contents as follows
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Professor Bai Ou first introduced the current status of DLBCL treatment and prognostic factors
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Although about 60% of DLBCL patients can be cured by R-CHOP, the prognosis of patients with relapsed and refractory (R/R) DLBCL is still poor
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In the past 20 years, with numerous studies exploring the epidemiology and biological heterogeneity of DLBCL, as well as the detailed classification of DLBCL, the prognostic factors of DLBCL patients have been continuously discovered
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The current prognostic factors affecting DLBCL patients include clinical factors such as age, lactate dehydrogenase (LDH) level, stage, extranodal involvement, and biological factors such as disease type, Ki-67 level, gene mutation, lymphocyte count, etc.

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Professor Bai Ou said that the current challenge of DLBCL treatment is to identify high-risk patients, improve the prognosis, and prolong the survival of R/R DLBCL patients
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How to identify high-risk patients with DLBCL Professor Bai Ou first introduced the research progress of DLBCL prognosis evaluation
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The results of the retrospective GELTAMO study were announced at this year’s EHA conference.
The study included 137 DLBCL patients who received R-CHOP regimens to evaluate the GELTAMO-IPI scoring system (including age, ECOG score, LDH level, disease stage, β2 microglobulin) Level and other factors) the accuracy of identifying high-risk DLBCL patients
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Under the GELTAMO scoring system, the 5-year OS rate of low-risk patients reached 100%, the 5-year OS rate of middle-low-risk patients was 65%, the 5-year OS rate of middle-high-risk patients was 51%, and the 5-year OS rate of high-risk patients was 18% (P <0.
001; HR: 22.
9)
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Compared with IPI, R-IPI, NCCN-IPI and other scoring systems, the GELTAMO-IPI scoring system can better identify high-risk DLBCL patients, but the number of patients included in the study is small, and it is still necessary to carry out follow-up studies to further verify the model to identify high-risk patients.
Accuracy in DLBCL patients
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 The REMARC study explored the value of the total metabolic volume (MTV) of the tumor assessed by PET/CT and the longest distance between two lesions (SDmax) as prognostic factors for DLBCL
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The results of the study showed that high SDmax is associated with poor progression-free survival (PFS) and OS in patients with DLBCL
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The study combined MTV and SDmax to divide DLBCL patients into 3 risk groups.
The results of the study showed that there were significant differences in the 4-year PFS rate and OS rate in each risk group
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The study also found that the combination of MTV, SDmax, and ECOG scores (including any 2 factors of high MTV, high SDmax, and ECOG score> 2) can effectively predict the recurrence of the central nervous system (CNS) of patients with DLBCL
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 Circulating tumor DNA (ctDNA) testing can also effectively assess the prognosis of patients with DLBCL
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A phase II study conducted by the Nordic Lymphoma Group (NLG) included 101 high-risk (aaIPI scores of 2-3 and/or CNS with high-risk factors) DLBCL patients younger than 65 years to evaluate the prognosis of ctDNA testing Value
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The results of the study announced at the EHA conference this year showed that DLBCL patients with high ctDNA expression before treatment had a lower complete remission (CR) rate, a higher risk of disease progression, recurrence, and death (P=0.
0078), and minimal residues in DLBCL patients after treatment MRD status is correlated with recurrence-free survival (P=0.
0026)
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How to optimize the first-line treatment of DLBCL Professor Bai Ou then introduced how to optimize the first-line treatment strategy of DLBCL
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A multicenter retrospective study announced at this year's EHA conference included elderly (>80 years) DLBCL patients and explored the correlation between different intensity treatments and OS
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The results of the study showed that the median OS of elderly DLBCL patients who received reduced-dose chemotherapy and full-dose chemotherapy was 2.
06 years and 1.
95 years, respectively, while the median OS of elderly DLBCL patients who received palliative chemotherapy and palliative treatment was only 0.
57 years and 0.
21 years
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For older patients with DLBCL, a reduced-dose chemotherapy regimen can be used clinically to improve the prognosis of patients
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 Another phase I/II study announced at this EHA conference explored the efficacy and safety of the bispecific monoclonal antibody Mosunetuzumab in the first-line treatment of elderly/poor DLBCL patients
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The study included 48 DLBCL patients with a median age of 83 years and ECOG scores ≤ 2 points
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At a median follow-up of 9.
4 months (range: 0.
2-22.
7), the overall response rate (ORR) of Mosunetuzumab in DLBCL patients reached 61.
5%, the CR rate reached 43.
6%, and 8 of the 17 patients who achieved CR after treatment ≥12 months are still in CR state, and Mosunetuzumab has good safety in DLBCL patients
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For elderly patients with DLBCL, the treatment strategy of reduced-intensity chemotherapy combined with new drugs is expected to bring a better prognosis
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 A study conducted by the Jiangsu Provincial People's Hospital explored the efficacy and safety of the R-CHOP regimen combined with zebutinib and lenalidomide (ZR2-CHOP regimen) in the treatment of patients with high-risk DLBCL aged 18-75 years
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The results of the study announced at this EHA conference showed that at a median follow-up of 5 months (range: 3-8), the ORR of high-risk DLBCL patients receiving the ZR2-CHOP regimen reached 100%, and the CR rate reached 90%.
It is well tolerated in DLBCL patients
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For patients with high-risk DLBCL, the combined program has the significance of further exploration
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 CD5 positive is also a high risk factor for DLBCL patients
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Although CD5+ DLCBL patients accounted for only 10% of DLBCL patients, the 5-year OS rate of these patients was only 34% (P=0.
0026)
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A clinical study announced at the ASCO conference this year explored the efficacy and safety of the R-DA-EPOCH regimen combined with high-dose methotrexate (HD-MTX) regimen in the treatment of CD5+ DLBCL patients
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At a median follow-up of 6.
0 years (range: 5.
0-7.
7), the 5-year PFS rate of the program reached 72% (95%CI: 57%-83%), and the 5-year OS rate reached 79% (95%CI: 64%) -88%), the 5-year CNS recurrence rate was 9% (95%CI: 3%-22%), and 7 patients had secondary tumors
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The efficacy of this combined program in patients with CD5+ DLBCL is worthy of recognition, but it is necessary to pay attention to toxic and side effects when using it
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 Genetically high-risk DLBCL patients can guide treatment selection through molecular stratification
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A phase II study conducted by Professor Zhao Weilai's team from Ruijin Hospital, Shanghai Jiaotong University School of Medicine, explored the efficacy of molecularly stratified guided R-CHOP+X regimens in newly treated patients with high-risk genetics DLBCL
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The research results announced at the ICML conference this year showed that compared with the R-CHOP program, the molecular-layered guided R-CHOP+X program had a higher CR rate (87% vs 66%; P=0.
003), and the 12-month PFS rate (93% vs 73%) and the 12-month OS rate (96% vs 85%) are also higher
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The treatment plan guided by molecular stratification can significantly improve the prognosis of patients with high-risk DLBCL, and it is worthy of further exploration
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Exploration of new drug treatment options for R/R DLBCL Professor Bai Ou finally introduced the research progress of new drugs for R/R DLBCL
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At present, the FDA has approved a variety of chimeric antigen receptor T cell (CAR-T) immunotherapies, monoclonal antibodies, antibody drug conjugates, and targeted drugs for the treatment of R/R DLBCL
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Professor Bai Ou said that new drugs and new therapies will be an important exploration direction for R/R DLCBL in the future
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 This year’s EHA conference announced the real-world efficacy data of CAR-T therapy in France.
The ORR of CAR-T therapy for R/R DLBCL reached 74.
2%, the CR rate reached 53%, and the 6-month PFS rate reached 44.
5% and 57.
7%.
Of patients’ remission lasted up to 6 months
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Within 10 days of CAR-T infusion, the incidence of cytokine release syndrome (CRS) was 81.
2%, the incidence of neurotoxicity was 35.
7%, and the incidence of ≥3 grade infection was 31.
7%
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The efficacy of CAR-T therapy in the real world is consistent with clinical research, but further exploration is needed to improve the efficacy of CAR-T therapy
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 The long-term follow-up results of the CD19 monoclonal antibody Tafasitamab combined with lenalidomide in the treatment of R/R DLBCL were announced at the ASCO conference this year
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The ORR of the combined program reached 57.
5%, the CR rate reached 40%, and the median duration of response (DOR) reached 43.
9 months
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At a median follow-up of 33.
9 months, the median PFS reached 11.
6 months (95%CI: 6.
3-45.
7); at a median follow-up of 42.
7 months, the median OS reached 33.
5 months (95%CI: 18.
3-NR)
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The combination regimen is well tolerated in R/R DLCBL patients and is expected to become a new treatment option for R/R DLBCL
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 The results of the study on the treatment of R/R DLBCL with the antibody-drug conjugate loncastuximab combined with ibrutinib were announced at the ICML conference this year
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The ORR of the combined regimen for R/R DLBCL reached 56.
7%, the CR rate reached 30%, and the median DOR reached 5.
5 months
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For patients with non-GCB R/RDLBCL, the ORR of the combined regimen reached 66.
7%, and the CR rate reached 37.
5%
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The combination regimen has good safety in R/RDLBCL patients, and it can also be used as a new treatment option for R/R DLBCL
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 This year's ASCO conference announced the results of the antibody-drug conjugate Polatuzumab vedotin (Pola) combined with rituximab and lenalidomide in the treatment of R/R DLBCL
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The ORR of the combined regimen in the treatment of R/R DLBCL reached 35%, and the CR rate reached 29%; the median PFS was 6.
3 months, and the median OS was 10.
9 months
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In the study, 11% of patients discontinued the drug due to adverse events (AEs), 67% of patients delayed or discontinued treatment due to AEs, and 26% of patients received dose reduction therapy due to AEs
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The combined program can also be used as a new option for the treatment of R/R DLBCL, but it is necessary to pay attention to the management of related AEs when using it
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Summary Professor Bai Ou finally concluded: Although the current treatment of DLBCL still has certain challenges, many new drugs and new therapies have shown considerable efficacy and safety in the treatment of DLBCL
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We look forward to more clinical studies in the future to further verify the efficacy and safety of these new drugs and new therapies, and to discover better drugs and treatment options to bring more treatment options to DLBCL patients and improve the prognosis of DLBCL patients
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Professor Bai Ou, Deputy Director, Department of Hematology, Bethune First Hospital, Jilin University, Head of the Lymphoma Specialist Alliance, Bethune First Hospital, Jilin University; Member of the Standing Committee of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association CSCO Member of the Standing Committee of the Chinese Anti-Lymphoma Alliance (UCLI) Member of the Standing Committee of the 5th Clinical Chemotherapy Committee of the Chinese Anti-Cancer Association Member of the Standing Committee of the First Committee of the Hematology Branch of the Chinese Society of Geriatrics Member of the Standing Committee of the Oncology Branch of the International Exchange Promotion Association CSCO Member of the Chinese Anti-Leukemia Alliance (UCLI) stamp "Read the original text", we make progress together