New progress in the treatment of relapsed and refractory DLBCL

"Club Yinghui - Lymphoma Diagnosis and Treatment Research Interpretation Series" is an exclusive academic exchange platform for young and middle-aged hematologis.
Through intensive reading of influential research literature in the field of lymphoma, discussion of hot topics in lymphoma diagnosis and treatment, and joint exploration and summary Optimized diagnosis and treatment strategies for lymphoma to improve the survival rate of Chinese lymphoma patien.
In this issue, Professor Tao Rong of Fudan University Affiliated Cancer Hospital and Professor Liu Yanyan of Zhengzhou University Affiliated Cancer Hospital served as the chairman of the conferen.
Professor Ma Jiexian of East China Hospital Affiliated to Fudan University and Professor Li Na of the Second Affiliated Hospital of Dalian Medical University explained the relapsed and refractory diffuse disease for everyo.
Frontier literature related to the treatment of B-cell lymphoma (DLBCL), and invited Professor Wang Xiaoxiao from Sun Yat-Sen University Cancer Hospital, Professor Huang Yan from Jiangxi Cancer Hospital, Professor Xu Lu from the First Affiliated Hospital of Hainan Medical College, and Tongji Medical College of Huazhong University of Science and Technolo.
Professor Zhou Xiaoxi from Tongji Hospital participated in the exchange and discussi.
The highlights of this session are now organized as follo.
Intensive literature reading (1) What should be done after R-CHOP treatment fails in DLBCL patients? Professor Ma Jiexian shared an article titled "Diffuse large B-cell lymphoma: R-CHOP failure—what to do?" published by the American Society of Hematolo.
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This review explores the causes and possible treatment options for DLBCL patients who have failed rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy, and has good guiding significan.
Analysis of patients with DLBCL who failed R-CHOP treatment DLBCL is the most common lymphoma, accounting for 25% of all lymphoproliferative disorde.
R-CHOP is the standard of care for patients with DLB.
About 50%-60% of patients can be cured with current standard treatment, but about 40%-50% of patients still experience refractory or relapse after treatme.
Among them, about 15%-25% of patients are primary refractory (progression during or after treatment), about 20%-30% of patients relapse after complete remission (CR), and some patients (<5%) No CR was achieved, but only partial remission (PR) (Figure
Figure 1 Outcomes of DLBCL patients after R-CHOP chemotherapy R-CHOP-refractory patients: Most patients with refractory lymphoma present with double-hit lymphoma (MYC-BCL2 rearrangement) (DHL) or double-expressing lymphoma (MYC -BCL2 high expression) (DPL), its clinical manifestations are more aggressi.
Studies targeting DHL or DPL have concluded that patients have poorer outcomes and that R-CHOP may not be the treatment of choi.
Patients with early relapse: Early relapse is usually defined as one year after diagnosis or 6 months after the end of treatme.

Although these patients achieved CR with treatment, they progressed rapidly and the lymphoma cells did not respond to subsequent treatments, which may be related to genetic heterogenei.

Patients with late relapse: Compared with refractory patients or patients with early relapse, patients with late relapse responded better to salvage chemotherapy and had longer progression-free survival (PFS) and overall survival (O.

However, at the time of diagnosis or when CR occurs, there is no way to identify patients who are likely to relapse, let alone differentiate between early and late relaps.

Exploration of treatment options after failure of R-CHOP in DLBCL is currently exploring new strategies to achieve higher CR rates and fewer recurrenc.

Although autologous transplantation can be performed after high-dose therapy in young relapsed patients, there is an unmet need for better salvage regime.
The following is a suggested treatment strategy for patients who have failed R-CHOP (Figure
FigureSuggested treatment strategies for patients who have failed R-CHOP thera.

Treatment strategies for refractory patients: Currently, there is no way to distinguish refractory patients, and patients are usually treated with standard R-CHOP therapy in the first li.

However, given the poor prognosis of patients with DHL, THL or DPL, focus on them and try to improve their first-line treatment optio.

Intensive R-CHOP is a relatively more effective treatment opti.

In a retrospective analysis, the MD Anderson team studied a total of 129 patients receiving R-CHOP, dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin ( DA-R-EPOCH) or rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone with high-dose methotrexate-cytarabine (R-hyperCVAD/MA) In patients with DHL who were alternately treated, it was found that patients who received DA-R-EPOCH or R-hyperCVAD/MA had better outcom.

Compared with R-CHOP, R-hyperCVAD/MA was significantly associated with higher CR rates, while DA-R-EPOCH treated EFS long.

However, intensive treatment regimens are not suitable for all patients and may be associated with higher toxici.

Therefore, regimens other than R-CHOP are more suitable for the treatment of high-risk patien.

Currently, several drugs that modulate MYC expression or activity are in clinical developme.

Treatment strategies for relapsed patients: Currently, no standard regimen has been established for patients with relapsed DLB.

To prolong PFS after salvage therapy, maintenance therapy should be consider.
Treatment strategies for patients with PR: Patients with PR may progress and require treatment before progressi.

Patients are usually given a standard salvage regimen (R-DHAP, R-ICE, or R-ESHAP) followed by autologous transplantati.

Summary R-CHOP does not seem to be a good treatment option for DHL or DPL, but there is no better soluti.

While new drugs targeting MYC and BCL2 are highly anticipated, it may take a long time to develop a good regim.

For relapsed patients, immunomodulators currently used to maintain CR are a strategy that may be applicable to both older and younger patien.

After the wonderful interpretation of Professor Ma Jiexian, the experts shared some experiences of autologous hematopoietic stem cell transplantation for high-risk DLBCL in the cent.

Several experts then discussed the treatment options for DLBCL patients who failed R-CHOP treatme.

Professor Xu Lu said that DLBCL does have a certain proportion of relapsed and refractory patients, and the treatment of relapsed patients has always been a hot spot in clinical resear.

Drug (ADC), double antibody, other new antibodies or small molecule drugs are listed or clinical data, and clinical needs to explore how to choose appropriate weapo.

Afterwards, Professor Liu Yanyan said that there are many confusions in salvage treatment for R/R DLBCL patien.

Currently, there are many new drugs and treatment plans in research, which also show that they can prolong surviv.

It is hoped that the benefits of these clinical studies can become clinical practi.

DLBCL has strong heterogeneity, different types of DLBCL have different pathogenesis, and the selection of drugs and treatment options will also be differe.

In recent years, some genome-related studies have initially shown therapeutic advantag.

There are more good literatures, Chinese people's own research, to answer clinical questio.
Intensive literature reading (2) Data update of Pola+BR in the treatment of R/R DLBCL Pr.

Li Na shared an article published by Blood Advances entitled "Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data (Polatuzumab Vedotin [hereafter referred to as Pola] in combination with bendamustine and rituximab in R/R DLBCL: survival update and new expansion cohort data)” [
This study evaluated the efficacy and safety of the Pola+BR regimen in the R/R DLBCL populati.

Study Design As of July 7, 2020, a total of 192 patients with R/R DLBCL were included in the study: Pola+BR group (n=152 [1b safety run-in, n=6; phase 2 randomization group, n=40; ​​expansion group] n=106), BR group (n=4
R/R DLBCL patients who were not eligible for transplantation received 6 cycles (21 days as a cycle) of Pola+BR or .

The expansion group had similar baseline characteristics to the randomized group (Figure
Figure 3 GO29365 Study Design The primary endpoint of randomization was CR rate at the end of treatme.

Secondary endpoints included safety, tolerability and efficacy, including objective response rate (ORR; CR or PR), best objective response (BOR), duration of response (DOR), PFS and .

The primary endpoints of the expansion arm included assessing the safety, PK profile and efficacy of Pola+.
Results As of the clinical cutoff date, the median follow-up time was 49 months and 43 months in the randomization group (Pola+BR and BR), respectively, and 12 months in the expansion gro.

In the randomized group, the significant survival benefit of Pola+BR vs BR as assessed by the Independent Review Committee (IRC) persisted (median PFS 2 months vs 7 months [HR, 39; 95% CI, 23-66; P &l.

0003]) (Figure 4-.

In the extension group, the median PFS assessed by IRC was 6 months (F.

4-.

Figure 4 Kaplan-Meier survival curves: PFS in the randomization group (A), PFS in the expansion group (B) In the randomized group, the median OS of Pola+BR vs BR assessed by IRC was 14 months vs 7 months [HR, 42; 95 %CI, 24-72; .

001]) (F.

5-.

In the extension group, the median OS as assessed by IRC was 15 months (F.

5-.

Figure 5 Kaplan-Meier survival curve: OS in randomization group (C), OS in expansion group (D) In ​​the expansion group, the ORR assessed by IRC was 45%, and the CR rate was 37%; in the randomization group, the Pola+BR group assessed by IRC Compared with the BR group, the BOR rates were 65% and 20%, respectively, and the best CR rates were 55% and 25%, respective.

In this study, the follow-up period was longer and no new safety issues were observ.

Table 1 Summary of efficacy results Subgroup analyses We performed an exploratory analysis of BOR, PFS, and OS in 152 patients who received Pola+.
The results showed that patients who benefited from the Pola+BR regimen: Compared with later-line therapy and refractory patients, patients who received Pola+BR early, patients who were not refractory had higher BOR, median PFS and .

In non-primary refractory patients and patients who received Pola+BR as second-line therapy, the efficacy benefit was significant, with median OS of 30 months and 14 months, respectively (Figure
Figure 6 Subgroup analysis IRC assessment of BOR (AC), IRC assessment to assess PFS (D), OS (E) Study Conclusions In the longer follow-up, the efficacy of the Pola+BR expansion group and the randomized group were similar; The survival benefit of BR persist.

Pola+BR is an effective option for the treatment of R/R DLBCL with favorable efficacy and manageable safety profi.

Experts' hot discussion After Professor Li Na's wonderful interpretation, many experts discussed the Pola+BR regimen in the treatment of R/RDLBC patien.

Pr.

Huang Yan and Pr.

Li Na discussed whether CD79 expression was detected when Pola was used in this stu.

Professor Li Na added that CD79 expression was detected in this study, but there was no difference in CD79 positive and negative results, and further large-scale studies are needed in the later sta.

Pr.

Yanyan Liu added that CD79 is expressed in almost all B-cell lymphomas, and as a target for targeted therapy, it may meet unmet clinical nee.

Subsequently, Professor Zhou Xiaoxi shared the clinical experience of Pola+BR bridging CAR-T cell therapy in his hospit.

Professor Wang Xiaoxiao said that from the data of subgroup analysis, the Pola+BR regimen is a good regimen in second-line, R/R DLBCL and primary drug-resistant patients, and he looks forward to having the opportunity to try this regimen in clinical practice in the futu.
Finally, Professor Tao Rong concluded that in general, R/R DLBCL is still a field with high unmet clinical nee.

With the clinical research and the launch of new drugs, more treatment options are availab.

For example, Pola with better evidence will soon come to the Chinese mark.

, It is also very critical for which specific patients can be used for the premise, especially patients who are not suitable for transplantation with 2L, and their treatment outcomes are significantly wor.

At the same time, Pola is also conducting research on the combined R-GemOx program, which is expected to further confirm the benefit of patients after
We look forward to Pola entering China as soon as possible, making it accessible to more patients and benefiting more patien.
This issue of "Club Yinghui - Lymphoma Diagnosis and Treatment Research Interpretation Series" has been successfully conclud.

See you in the next issue! In the next issue, we will be previewing Qunyinghui | Lymphoma Diagnosis and Research Interpretation Series - Session 5, Qunyinghui | Interpretation Series of Lymphoma Diagnosis and Treatment - The Eighth Review of Past Issues, Issue 1 | New Thinking on the Diagnosis and Treatment of Initial DLBCL with Literature Accuracy, Issue 2 | Issue 3 | New progress in the treatment of rituximab-refractory iNHL in intensive literature review --what to d.

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