Application of anti-CD20 monoclonal antibody in lymphoma

"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 Wang Xiaobo of the Second Affiliated Hospital of Dalian Medical University and Professor Du Juan of Shanghai Changzheng Hospital served as the chairman of the conferen.
Professor Wang Yun of Sun Yat-sen University Cancer Center and Professor Ping Lingyan of Peking University Cancer Hospital explained the combination of anti-CD20 monoclonal antibody in the treatment of lymph nod.
Frontier literature related to cancer, and invited Professor Ye Jingjing from Qilu Hospital of Shandong University, Professor Wang Liang from Beijing Tongren Hospital Affiliated to Capital Medical University, Professor Wang Wei from Qingdao University Affiliated Hospital, and Professor Liu Haisheng from the Fourth Hospital of Hebei Medical University to participate in the exchange and discussi.
The highlights of the meeting are organized as follo.
Intensive Literature Reading (1) G-atezo-len regimen may be a new treatment option for R/R FL patients Pr.
Yun Wang shared an article published in Blood Cancer Journal entitled "Obinutuzumab-atezolizumab-lenalidomide for the treatment of patients with relapsed /refractory follicular lymphoma: final analysis of a Phase Ib/II trial (octuzumab-atezolizumab-lenalidomide [G-atezo-len] in relapsed/refractory follicular lymphoma) [R/R FL]: Final Analysis of Phase Ib/II Trials)” article [
In this study, the chemotherapy-free triple regimen G-atezo-len showed good efficacy and manageable safety in the induction and maintenance therapy of R/R FL patien.
Study Design This is a Phase Ib/II, open-label, multicenter, non-randomized stu.
A total of 38 patients with R/R FL who received ≥1 prior anti-CD20-containing mAb therapy were included, with a median age of 65 years (38-79), and 79% of the patients had Ann Arbo stage III/IV at diagnos.
The study included induction therapy and maintenance therapy phas.
During the induction treatment phase, patients received 6 cycles (28 days/cycle) of octuzumab 1000mg + atezolizumab 840mg + lenalidomide (15 or 20m.
Patients who achieved complete remission (CR), partial remission (PR) or stable disease (SD) at the end of induction therapy continued to receive G-atezo-len maintenance therapy (octuzumab 1000mg + atezolizumab 840mg + lenadulum amine 10m.
Treatment was maintained for 24 months or until disease progression, unacceptable toxicity, or discontinuation of treatment for other reaso.
The primary endpoint of the study was independent review committee (IRC)-assessed CR at end of induction therapy (EO.
The safety endpoint was the incidence of adverse events (AE.
Secondary endpoints included CR rate at EOI (investigator [INV]-assessed, combined IRC&INV assessment) and objective response rate (ORR, CR or PR) at EOI (combined IRC&INV assessmen.
Exploratory endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), and ORR and CR rates for EOI in patients with or without disease progression within 24 months (POD24) after first-line thera.
Finally, 38 patients (lenalidomide 15 mg, n=4; 20 mg, n=34) completed the study, 31 patients completed induction therapy, and 27 patients completed maintenance thera.
At the end of induction, the response population (lenalidomide 20 mg, n=32) had an IRC-assessed CR rate of 79% (Table 1) and an INV-assessed CR rate of 7
The 36-month PFS rate was 64% (95% CI, 48-82) (Figure 1), and the 36-month OS rate was 90% (95% CI, 72-9
Table 1 Summary of main study results (lenalidomide 20 mg, n=32) Figure 1 Kaplan-Meier curve: PFS (INV assessment) median DOR in R/R FL patients was 38 months (95% CI, 35-not possible) estimated), 24 patients (70%) who received G-atezo-len maintenance therapy had durable clinical responses (>1 year), and 18 patients had clinical responses lasting >36 months (Figure
Figure 2 DOR (INV assessment) >>>> subgroup analysis of 32 patients treated with G-atezo-len in dual refractory (rituximab and alkylating agent refractory) patients (n=12) , the CR rate (IRC assessment) was 67% (95%CI, 31-87; ORR 67%), while the CR rate in non-refractory patients was 70% (95%CI, 54-86; ORR 80%) (P =696
In POD24 patients (n=12), the CR rate (IRC assessment) was 50% (95% CI, 25-75; ORR 53%) compared to 80% (95% CI, 66-98) in non-POD24 patients ; ORR 90%) (P=049
>>>>Safety No new safety signals were found, AEs were consistent with each drug, and no patients discontinued the study due to A.
Conclusions This study showed that the G-atezo-len regimen was effective and tolerable in R/R FL patients, with an EOI CR rate of 79% and a 36-month PFS rate of 6
No new safety signals were fou.
.
Expert hot discussion After Professor Wang Yun's wonderful interpretation, many experts discussed the application of the new G-base treatment plan in R/R .
Professor Ye Jingjing said that ortuzumab has been proven in multiple studies for R/R FL patients, which can effectively reduce disease progression and improve patient prognos.
In this study, the G-atezo-len regimen had a good effect in the treatment of R/R FL patients, and the 36-month PFS rate was 6
Another article published in Blood evaluated the G-len regimen in patients with R/R FL and showed that the octuzumab combination was superior to the rituximab combination in 66 patients with relapsed iN.

In the phase I/II study of the FL subgroup (n=57), the 24-month PFS was 74%, the ORR was 100%, and the CR was 75%; compared with the previous study of rituximab combined with lenalidomide in the treatment of R/ The data response rate was higher in RFL patients (ORR 70%, CR 41.

Professor Wang Liang added that for the post-line treatment of FL patients, patients who have not used otuzumab in the front-line treatment can try .

On the one hand, as a new humanized anti-CD20 mAb, octuzumab has a unique mechanism of action and no cross-resistance with rituximab; Targeted drugs for full coverage of induction and maintenance thera.

Otuzumab can be used as the cornerstone of therapy in combination with other small molecule targeted drugs in the treatment of R/R FL in the later li.

Professor Du Juan said that when choosing a treatment plan, in addition to the factors of the disease, it is also necessary to consider the patient's age, physical state, and drug price, and recommend a treatment plan that can bring more benefits to the patie.
Intensive literature reading (2) Application of anti-CD20 monoclonal antibody in B-cell lymphoma: current situation and future Pr.

Ping Lingyan shared an article titled "Anti-CD20 treatment for B-cell malignancies: current published by Expert Opinion on Biological Therapy" status and future directions (the application of anti-CD20 monoclonal antibody in B-cell lymphoma: status and future)” article [
This study systematically reviewed the development of anti-CD20 mAb and its application in B-cell lympho.

The status of anti-CD20 monoclonal antibodies was significantly improved in the 1990s with the first anti-CD20 monoclonal antibody, rituximab, the treatment of B-cell malignanci.

Enhanced activity in lymphoma (NHL) and chronic lymphocytic leukemia (CLL), as well as against cytotoxic chemotherapy in lymphoma, significantly improves outcomes in patients with B-cell malignancies as follicular lymphoma (FL) , standard of care for diffuse large B-cell lymphoma (DLBCL) and C.

Despite these successes, many patients relapse, and retreatment after relapse has diminished efficacy, reduced DOR, and patients may become refracto.

This prompted researchers to search for novel anti-CD20 monoclonal antibodies that differ structurally and mechanistically from rituxim.

Novel anti-CD20 monoclonal antibodies Anti-CD20 monoclonal antibodies can be divided into type I and type .

Type I includes rituximab, ofatumumab, and Ublituxim.

Otuzumab belongs to type II (Table
Type I monoclonal antibodies usually have complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC); type II monoclonal antibodies have ADCC and antibody-dependent cell-mediated phagocytosis (ADCP), Direct cell death (DCD) increases and CDC decreas.
Otuzumab is the world's first humanized and glycosylated type II anti-CD20 monoclonal antibody; Ofatumumab is a fully humanized type I anti-CD20 monoclonal antibody with unmodified Fc segment; Ublituximab It is a chimeric type I anti-CD20 monoclonal antibody whose Fc segment is modified by glycosylati.

Table 2 Anti-CD20 monoclonal antibodies and their properties Important studies of novel anti-CD20 monoclonal antibodies (aNHL) pivotal stu.

Of the novel anti-CD20 antibodies, only octuzumab demonstrated superiority to rituximab in randomized pivotal trials in iNHL and C.

Data from the Phase 3 CLL11 and GALLIUM trials demonstrated that octuzumab-based immunochemotherapy improved clinical outcomes in patients with CLL and iNHL, respectively, including PFS, OS, and baseline compared with rituximab-based immunochemothera.

Time to next treatment and minimal residual disea.

Table 3 Survival rates and adverse events in pivotal clinical studies of novel anti-CD20 mAbs in CLL patients Table 4 Survival rates and adverse events in pivotal clinical studies of novel anti-CD20 mAbs in patients with iNHLTable 5 Novel anti-CD20 mAbs in patients with aNHL Summary of survival and adverse events from pivotal clinical studies in the type I anti-CD20 mAb, rituximab, has significantly improved the treatment of B-cell malignancies, but there remains an unmet ne.

Relapse and refractory still plague many patients, and the new anti-CD20 mAb octuzumab has enhanced pharmacodynamic properties relative to rituximab, and some trials in patients with CLL or iNHL have shown greater benef.

There are also many new combinations of octuzumab being explored, including chemotherapy-free options, such as the newly approved octuzumab in combination with veneclax, ibrutinib, or acalabrutin.
Expert Hotspot Discussion After Professor Ping Lingyan's wonderful interpretation, many experts discussed the exploration of new combination therapy of otuzum.

Professor Wang Wei said that BTK inhibitors are widely used in CLL, but require long-term treatment and have limited efficacy in high-risk patien.

For young patients and low-risk patients, limited treatment with octuzumab combined with BTK inhibitors can be tried mo.

Professor Liu Haisheng added that although oral medication is convenient, it needs to be differentiated for different types of patien.

Although cost is an important consideration, an economical combination plan can be considered to bring more clinical benefits to patien.

Professor Du Juan said that for the treatment of any disease, we all hope to achieve deep remission, but at the same time, we hope to save the cost of patient treatme.

The data of veneclax research has good curative effect, but the domestic price is still high and the availability is not stro.

However, based on foreign experimental data, we can try to combine anti-CD20 monoclonal antibody in the later li.

In the end, Professor Wang Xiaobo said that both in terms of economy and depth of remission, he hopes to have a stronger combinati.

In addition, in the treatment plan for chronic lymphoma, chemotherapy-free and limited-cycle treatment is an important direction for our future explorati.


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See you in the next issue! The next preview of Qunyinghui | Lymphoma Diagnosis and Treatment Research Interpretation Series - the seventh session of Qunyinghui | Thinking Qunyinghui·.

2| Intensive Literature Reading Focused on the Treatment of Indolent Lymphoma·Qingyinghui·.

3 | Literature Intensive Reading: New Progress in the Treatment of Rituximab-Refractory iNHL New progress in the treatment of relapsed and refractory DLBCL Review references:Morschhauser F, Ghosh N, Lossos IS, et .

Obinutuzumab-atezolizumab-lenalidomide for the treatment of patients with relapsed/refractory follicular lymphoma: final analysis of a Phase Ib/II trial[.

Blood cancer journal, 2021, 11(8): 1- Klein C, Jamois C, Nielsen.

Anti-CD20 treatment for B-cell malignancies: current status and future directions[J.

Expert Opinion on Biological Therapy, 2021, 21(2): 161-18 Editor: SXJ Reviewer: Evelyn Typesetting: Wenting Execution: Quinta Poke "read the original text" to see more content