The treatment of indolent lymphoma focuses on the intensive reading of the 2nd issue of Qunyinghui.

The introduction of "Club Yinghui - Lymphoma Diagnosis and Research Interpretation Series" is an exclusive academic exchange platform for young and middle-aged hematologists.
To summarize the optimized diagnosis and treatment strategies for lymphoma to improve the survival rate of Chinese lymphoma patients
.

In this issue, Professor Li Yuhua of Pearl River Hospital of Southern Medical University and Professor Xue Hongwei of Affiliated Hospital of Qingdao University are the chairmen of the conference.
Professor Lin Zhijuan of the First Affiliated Hospital of Xiamen University and Professor Zheng Runhui of the First Affiliated Hospital of Guangzhou Medical University will interpret the cutting-edge literature in the field of indolent lymphoma.
, and invited Professor Sang Wei from the Affiliated Hospital of Xuzhou Medical University, Professor Wei Xiaolei from the Southern Hospital of Southern Medical University, Professor Li Xiaoqing from the Second People's Hospital of Shenzhen and Professor Zhu Huayuan from the Jiangsu Provincial People's Hospital to participate in the exchange and discussion.
The highlights of this session are now organized as follows
.

Intensive literature reading (1) Otuzumab is safe and effective for rituximab-refractory or relapsed FL patients Prof.
Lin Zhijuan shared an article published by Targeted Oncology entitled "Obinutuzumab: A Review in Rituximab-Refractory or –Relapsed Follicular Lymphoma (Otuzumab: A review of rituximab-refractory or relapsed follicular lymphoma)” [1]
.

This review focuses on the pharmacodynamics/pharmacokinetics, efficacy and safety of octuzumab in the treatment of follicular lymphoma (FL).
guiding significance
.

A brief description of the unique mechanism of octuzumab octuzumab is the world's first type II humanized anti-CD20 monoclonal antibody that has undergone glycosylation.
The Fc region of octuzumab is glycosylated, which enhances the affinity activation of immune effector cells, enhances antibody-dependent cell-mediated cytotoxicity (ADCC), and phagocytosis.
(ADCP) and direct cell death (DCD), reducing complement-dependent cytotoxicity (CDC); in addition, octuzumab has a unique CD20 antigen-recognition epitope, which does not lead to CD20 clustering into lipid rafts and Endocytosis, making anti-CD20 mAbs more durable, induces marked homotypic adhesion and direct cell death of CD20-positive cells
.

In terms of the pharmacokinetics of special populations, the pharmacokinetics of octuzumab in the elderly population was not significantly different from that in young patients; in addition, the results of the pharmacokinetics and pharmacology studies conducted in China showed that octuzumab in the Chinese patient population was not significantly different.
The pharmacokinetic profile of the drug is highly consistent with the European and American patient populations
.

The Efficacy and Safety of Ortuzumab in Relapsed and Refractory FL The GADOLIN study is a global, multicenter, randomized, controlled Phase III clinical study in patients with indolent lymphoma relapsed and refractory to rituximab (FL, MZL, small lymphocytic lymphoma [SLL]) patients were treated with bendamustine monotherapy and octuzumab combined with bendamustine (GB regimen), respectively
.

Results showed that compared with bendamustine monotherapy, GB regimen significantly improved progression-free survival (PFS) in patients with relapsed or refractory indolent lymphoma and reduced the risk of death by 33%; data in the FL subgroup Consistent with the general population data, the GB regimen reduced the risk of disease progression and death in FL patients by 48% relative to monotherapy
.

In terms of overall adverse reactions, there were no unexpected safety events
.

GB regimen is a better treatment option for FL patients refractory to rituximab
.

The better efficacy of octuzumab combined with lenalidomide (Glen) regimen in R/R FL patients is also worthy of attention
.

The results of a phase II study showed that the overall response rate (ORR) of otuzumab combined with Glen in the treatment of R/R FL reached 100%, and the complete response and indeterminate complete response (CR/CRu) rate reached 75%
.

SUMMARY Given the efficacy and tolerability of octuzumab, octuzumab in combination with bendamustine followed by octuzumab maintenance is approved in the United States and the European Union for the treatment of rituximab-refractory or patients with relapsed FL and marginal zone lymphoma (MZL)
.

Although further studies will help confirm the therapeutic benefit of octuzumab in patients with FL, current evidence suggests that octuzumab is an effective option for patients who relapse or are refractory to rituximab-containing regimens
.

Expert hotspot discussion After Professor Lin Zhijuan's wonderful interpretation, many experts discussed the application of otuzumab in FL
.

Professor Zhu Huayuan said that in the post-marketing use of octuzumab in FL patients, it was found that compared with the first-generation anti-CD20 monoclonal antibody, octuzumab had significant benefits in terms of efficacy
.

A rapid onset of effect was observed, especially after modification of the chemotherapy regimen in transformed high-grade FL patients
.

Subsequently, Professor Lin Zhijuan said that in terms of the selection of rituximab and octuzumab, it is recommended that FL that has not transformed should choose octuzumab for treatment
.

Subsequently, Professor Li Xiaoqing and Professor Lin Zhijuan discussed the problem of hepatitis B virus reactivation after the application of otuzumab.
Professor Lin Zhijuan said that the previous literature showed that compared with rituximab, there is no very high incidence
.

Intensive literature reading (2) Ortuzumab may become a new choice for newly diagnosed MZL patients Prof.
Runhui Zheng shared an article published by Future Oncology entitled "Phase II trial evaluating the efficacy and safety of the anti-CD20 monoclonal antibody obinutuzumab in patients with marginal zone lymphoma (Phase II study of the efficacy and safety of anti-CD20 monoclonal antibody octuzumab in the treatment of marginal zone lymphoma [OLYMP-1 study])” [2]
.

This study is the first single-arm, open-label, multicenter Phase II study to evaluate octuzumab in marginal zone lymphoma (MZL) and aims to evaluate the efficacy and safety of octuzumab in treatment-naïve patients with MZL , the study will explore the efficacy and safety of continuing octuzumab maintenance therapy in MZL after octuzumab single-agent induction therapy
.

Background MZL belongs to indolent B-cell non-Hodgkin's lymphoma (B-NHL), which is characterized by a slow course of disease and is more common in the elderly
.

There is currently no clear standard of care for patients with MZL
.

The randomized IELSG-19 study assigned treatment-naive patients with MZL to receive chlorambucil monotherapy, rituximab + chlorambucil, and rituximab monotherapy, and rituximab monotherapy.
The ORR was 78.
3%, and the CR rate was 55.
8%; while the rituximab + chlorambucil group was 94.
7% and 78.
8%, respectively, indicating that rituximab combined with chemotherapy has a good effect in the treatment of MZL
.

In the GALLIUM study, 195 patients with MZL were randomized to receive rituximab + chemotherapy followed by rituximab maintenance therapy, and octuzumab + chemotherapy followed by octuzumab maintenance therapy, the results showed Response and PFS rates were similar for MZL patients in both cohorts
.

To further improve safety, the development of mild chemotherapy-free regimens has received much attention
.

In this setting, monotherapy with the novel anti-CD20 monoclonal antibody octuzumab is an attractive approach, with high efficacy without major toxicity
.

The purpose of this study was to analyze the efficacy and safety of otuzumab, assuming that this treatment is superior to rituximab alone and approaches the efficacy of immunochemotherapy without causing chemotherapy-related side effects
.

In this case, octuzumab monotherapy has the potential to become a new option for MZL patients
.

Eligible patients for the study design must be ≥18 years of age, CD20 positive, in need of treatment, not suitable for local therapy (such as surgery or radiotherapy), and with good bone marrow function
.

The study ultimately included 56 patients, including 28 with extranodal mucosa-associated lymphoid tissue lymphoma (EMZL), 14 with splenic marginal zone B-cell lymphoma (SMZL), and 14 with nodal marginal zone lymphoma (NMZL)
.

Patient enrollment began in January 2019, and eligible patients received octuzumab induction therapy followed by octuzumab maintenance therapy (Figure 1)
.

The primary endpoint was CR rate, secondary endpoints included remission rate (CR, partial remission [PR] and ORR [CR or PR]), best remission rate, time to best remission, time to first remission, PFS, to Time to treatment failure, duration of remission, OS, safety, and quality of life
.

Figure 1.
Study design Study summary and outlook Otuzumab, a novel anti-CD20 mAb, has shown significant activity in FL and other B-NHLs such as chronic lymphocytic leukemia (CLL)
.

In previous studies, octuzumab toxicity was manageable, and octuzumab plus chemotherapy was significantly better than rituximab plus chemotherapy in FL and elderly CLL patients
.

Tables 1 and 2 summarize the efficacy and safety results of previous studies on octuzumab
.

Table 1 Selected efficacy data for octuzumab/rituximab in comparative clinical studiesTable 2 Selected adverse event data for octuzumab/rituximab in comparative clinical studies Known activity and toxicity profile of tuximab as a single agent, the OLYMP-1 study used octuzumab monotherapy in MZL patients, the results of this study will help to understand whether octuzumab monotherapy Provides excellent tumor control rates and a favorable safety profile for treatment-naïve MZL
.

This will further assist in evaluating the feasibility of octuzumab maintenance therapy following octuzumab induction in MZL patients
.

Experts' Hot Discussion After Professor Zheng Runhui's wonderful interpretation, many experts discussed the attempt of otuzumab in MZL patients
.

Professor Xue Hongwei said that in the GALLIUM study, the small number of MZL patients enrolled and the unbalanced base may be one of the reasons why it did not see a significant effect
.

At the same time, the analysis of MZL is a retrospective evaluation, rather than a prospectively defined analysis, and more studies are expected to further explore the role of otuzumab in MZL
.

In addition, otuzumab has been approved abroad for the treatment of R/R MZL, FL, and CLL/SLL
.

Professor Zheng Runhui added that the clinical research and practice of octuzumab for the treatment of MZL are also being explored, and China can also try to apply octuzumab in MZL as a second-line re-induction and maintenance therapy
.

Prof.
Sang Wei said that anti-CD20 monoclonal antibody is the cornerstone of the treatment of indolent lymphoma, and the combination of anti-CD20 monoclonal antibody and new drugs is expected to improve the prognosis of high-risk patients
.

Subsequently, Professor Li Yuhua added that at present, octuzumab has advantages in the treatment of indolent lymphoma, and can reduce the early recurrence rate and prolong PFS.
The era of monoclonal antibodies"
.

This issue of "Club Yinghui - Lymphoma Diagnosis and Treatment Research Interpretation Series" has been successfully concluded.
See you in the next issue! The next preview of Qunyinghui | Lymphoma Diagnosis and Treatment Research Interpretation Series Session - The third Qunyinghui | Lymphoma Diagnosis and Research Interpretation Series - Fourth Review of Past Issues Qunyinghui·Issue 1 | References in the live review section of Thinking Group: 1.
Sohita Dhillon.
Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma.
Target Oncol.
2017 Apr;12(2):255-262.
017-0485-6.
2.
Alexander Grunenberg, Lisa M Kaiser, Stephanie Woelfle, et al.
Phase II trial evaluating the efficacy and safety of the anti-CD20 monoclonal antibody obinutuzumab in patients with marginal zone lymphoma.
Future Oncol.
2020 May;16( 13): 817-825.
doi: 10.
2217/fon-2020-0071.
Edit: Quinta Typesetting: Wenting pokes "read the original text", let's make progress together