Big coffee explores "Ao" anti-CD20 monoclonal antibody "Big Brother" starts well, "new generation" high starting point helps lymphoma diagnosis and treatment

With the continuous improvement of the level of diagnosis and treatment in recent years, and the application of more and more new drugs and technologies, the survival of lymphoma has been further improved
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Especially for B-cell non-Hodgkin's lymphoma (B-NHL), since the advent of the first generation of anti-CD20 monoclonal antibody-rituximab, the clinical treatment outcome of most patients has been significantly improved.
Rituxan Antibiotics have become the cornerstone of many B-NHL treatments
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Medicine has never stopped exploring forward.
With a new generation of anti-CD20 monoclonal antibody-Otuzumab approved for marketing and application in China, a very real problem lies in front of clinicians and patients: two anti-CD20 monoclonal antibodies.
How to choose resistance? How to better benefit patients? Are the two complementary or opposite? In this regard, Yimaitong specially connected with Professor Huang Wenrong of the Fifth Medical Center of the Chinese People's Liberation Army General Hospital to discuss this issue
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Yimaitong: You have been committed to the treatment of lymphoma and have a very deep experience in the use of drugs in the field of lymphoma.
Can you briefly introduce these two anti-CD20 monoclonal antibodies? Professor Huang Wenrong believes that everyone is already very familiar.
Rituximab is the first anti-CD20 monoclonal antibody.
It has been in clinical use for more than 20 years since it came out in 1997 and has brought significant benefits to the survival of many B-NHL patients.
, Is an epoch-making medicine
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Before the advent of otuzumab, rituximab has always been the cornerstone of the treatment of B-NHL, including some T-cell lymphomas
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Otuzumab is the first type II humanized anti-CD20 monoclonal antibody that has been glycosylated
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Compared with human-mouse chimeric rituximab, humanized otuzumab has lower immunogenicity, longer half-life and more stable, antibody-dependent cytotoxicity (ADCC) and direct cytotoxicity (DCD) is also stronger
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Otuzumab was first launched in Europe in 2011, and was first used in chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).
It is currently used in many other B-NHLs, especially lazy lymphoma.
Explore and try
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Yimaitong: Do you think they are complementary or opposed? What is the main reason? Can you talk briefly about it? Professor Huang Wenrong Although both rituximab and otuzumab are anti-CD20 monoclonal antibodies, there is a certain competitive relationship, but for clinicians, there is no doubt that we have one more anti-CD20 monoclonal antibody in our hands.
Weapons, there is also a choice
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One more choice, one more opportunity, so I think the relationship between them is more complementary than opposed
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I think the complementarity is mainly reflected in three aspects: 1.
From the current research data and real-world use, rituximab cannot be shaken as the cornerstone of the first-line treatment of aggressive lymphoma, while otuzumab is in The advantages are obvious in indolent lymphoma (iNHL)
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The GOYA study showed that otuzumab did not get superior results in the first-line treatment of diffuse large B-cell lymphoma (DLBCL), although in exploratory analysis, G-CHOP (Otuzumab/ Cyclophosphamide/doxorubicin/vincristine/prednisone) in the benefit trend of GCB subtypes, but the status of rituximab in the first-line treatment of DLBCL is still unshakable
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However, in iNHL, especially FL and CLL, otuzumab has obvious advantages, with the most evidence and the highest level of evidence
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In addition to FL and CLL, there are also routine recommendations for relapsed and refractory marginal zone lymphoma (MZL) in the NCCN guidelines
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In addition, from the currently registered iNHL-related clinical studies, the selected anti-CD20 monoclonal antibodies are almost all otuzumab, which also confirms the cornerstone position of otuzumab in iNHL
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2.
For patients who are resistant to rituximab, otuzumab is also a better treatment option
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As mentioned above, there was only one anti-CD20 monoclonal antibody-rituximab.
Once rituximab resistance appears, patients cannot continue to benefit from rituximab treatment.
For patients It is also a very big loss
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The unique mechanism of action and binding site of otuzumab (Figure 1) may overcome the resistance of rituximab and enable patients to regain benefit from anti-CD20 monoclonal antibody treatment
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The lymphoma transplantation model (DLBCL cell line) also showed that after the first-line rituximab treatment progressed, the otuzumab treatment still had a significant response (Figure 2)
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 Figure 1 Figure 2 The results of the GADOLIN study showed that compared with bendamustine alone, the sequential otuzumab maintenance regimen after induction of otuzumab combined with bendamustine significantly prolonged rituximab resistance The survival time of iNHL patients with drugs (Figure 3)
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Figure 3 For aggressive lymphomas resistant to rituximab, such as DLBCL, we also look forward to more research data to confirm the effectiveness of otuzumab
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In short, for patients who are resistant to rituximab, clinicians have another weapon against CD20 monoclonal antibody, giving patients one more choice and one more opportunity
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3.
Due to immunogenicity and other reasons, patients who are intolerant to rituximab can try otuzumab
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In the real world, a small number of patients will experience intolerance during rituximab infusion, and may stop using rituximab in the past, causing patients to lose their gains from anti-CD20 monoclonal antibody treatment.
Opportunity
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Now that humanized type II otuzumab is available, patients may tolerate otuzumab treatment due to differences in immunogenicity, giving patients the opportunity to continue to benefit from anti-CD20 monoclonal antibody treatment
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In summary, I think that the complementarity between otuzumab and rituximab is greater than the opposition.
The two anti-CD20 monoclonal antibodies give clinicians an extra weapon and benefit more lymphoma patients
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It is expected that with the continuous application of otuzumab in China, the overall survival of patients with B-cell lymphoma will be further improved
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Professor Huang Wenrong, Doctor of Medicine, Chief Physician, Master Tutor, Director of Lymphoma-Plasma Cell Disease Department, Department of Hematology, PLA General Hospital, Deputy Chairman, Lymph, Hematology, and Tumor Committee, Beijing Anti-Cancer Association, Vice Chairman, Hematology Committee, Chinese Society of Geriatrics The subject person in charge of the Standing Committee of the Blood Precision Diagnosis and Treatment Committee of the Chinese Research Hospital Association is responsible for the National Natural Science Foundation, the military project, and the capital health development scientific research project
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Won the second prize of Army Science and Technology Progress Award 1 first author or corresponding author published 21 clinical SCI papers in international journals such as Oncogene, Bone marrow transplant, Cell Transplantation, Frontier Oncology, Transfusion, Annals of Hematology, Clinical transplant, Leukemia & lymphoma, etc.
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