The innovative CD20 monoclonal antibody set sail in the wave of standardized treatment of indolent lymphoma

Q4: What else can we do to advance the standardized treatment of many types of iNHL?

▎Professor Yang Haiyan:

The emergence of anti-CD20 monoclonal antibodies has revolutionized the treatment paradigm
of iNHL.
Ointarzumab is the world's first humanized glycosylated type II CD20 monoclonal antibody, its innovative mechanism and PK advantages significantly prolong the PFS of patients, optimize the existing treatment mode, and have been explored and progressed in the treatment of multiple iNHL subtypes, including MZL, FL, CLL/SLL, MCL, MCL, etc
.

The GADOLIN Phase III study ^[15] compared the effects
of relapsed and refractory iNHL (FL, MZL, SLL) patients with rituximab who received obintaruzumab plus bendamustine (GB) versus bendamustine monotherapy (B group), respectively.
Long-term follow-up analysis showed that compared with group B^, the median PFS in the GB group was significantly longer (25.
8 months vs 14.
1 months), the risk of disease decreased by 43% (HR=0.
57, P<0.
0001), the median overall survival (OS) was longer than that in group B (88.
3 months vs 65.
6 months), and the risk of death was reduced by 33% (HR=0.
77, P=0.
0810) <b20>。 Among them, the data of the FL subgroup were basically consistent with the general population data, and the GB regimen reduced the risk of disease progression and death in FL patients by 48%
compared with monotherapy.
In terms of overall adverse effects, there were no unexpected safety events ^[16], suggesting that GB regimens are a new treatment option
for patients with FL who have progressed after rituximab treatment.

For the treatment of MCL, the combination regimen of obinutuzumab has shown good efficacy and safety in the treatment of patients with relapsed and refractory MCL:

• The efficacy of ibrutinib + obinutuzumab + Venetoclax was investigated in the OASIS study, and the results showed ^{that the} 1-year PFS and OS rates in patients with treatment-naïve MCL were 93.
  3% and 100%, respectively.
  The 2-year PFS and OS rates of patients with relapsed and refractory MCL were 69.
  5% and 68.
  6%,
  respectively.
  

• A phase II trial showed that zebratinib + obinutuzumab + veneclax (BOVen regimen) demonstrated good efficacy, tolerability, and safety
  in the treatment of treatment-naïve TP53-mutant MCL.
  Studies ^{have shown [17]}, with a median follow-up of 4 months, with an objective response rate (ORR) of 86% and a complete response (CR) rate of 64%.
  
  

• The LyMa-101 study explored the efficacy and safety of obinutuzumab + dexamethasone + cisplatin + cytarabine (G-DHAP) regimen in the first-line treatment of transplant-eligible MCL ^[17].
  The results showed that at the end of induction therapy with G-DCAP regimen, 92% (78/85) of patients achieved remission, 79% (67/85) of patients achieved CR, PFS rate and OS rate at 12 months were 94% and 96%, respectively, and bone marrow MRD negative rate reached 75%, suggesting that G-DCAP regimen is a new first-line induction therapy option
  for transplant-eligible MCL patients.
  

FOR THE TREATMENT OF CLELL, THE RESULTS OF THE FIVE-YEAR FOLLOW-UP OF THE ELEVATE-TN STUDY WERE UPDATED AT THE 2022 AMERICAN CLINICAL ONCOLOGY SOCIETY (ASCO) ^{ANNUAL MEETING [19].}

。 The results showed that the median PFS of the A+O group and the A group was significantly higher than that of the O+Clb group at a median follow-up of 58.
2 months, P< 0.
0001, A+O vs.
O+Clb: HR=0.
11; A vs.
O+Clb: HR=0.
21], and the estimated 5-year PFS rates of A+O and A were 84% and 72%, respectively, and the estimated 5-year overall survival rates were 90% and 84%.
<b12> This study confirmed that obinutuzumab combination therapy can bring long-term survival benefits
for treatment-naïve CLL through long-term follow-up.

In fact, obinutuzumab has been used internationally for many years and has been approved for marketing in nearly 100 countries, and its relevant clinical results have been released
at conferences such as ASH, ASCO, EHA and so on.
The innovative CD20 monoclonal antibody obinutuzumab can still produce antitumor activity in patients with disease progression resistance after rituximab treatment, showing good efficacy and safety
.

In order to achieve better prognosis and quality of life for iNHL patients, on the one hand, it is still necessary to increase investment in the field of innovative drug research and development, accelerate the speed of new drug research and development, and ensure the quality of
new drug research and development.
Scientific and technological innovation is the primary productive force
for improving the level of treatment.
Only the innovation of tumor drugs can have the possibility
of tumor cure.
With the further development and improvement of clinical research, basic scientific research and translational medicine, it will greatly promote the improvement
of the treatment level of hematological tumors.
On the other hand, further promotion of standardized treatment of iNHL can improve the level of clinical standard medication and help improve the treatment response rate and survival rate
of patients.
Accelerating the process of standardized treatment in China is a key step, and clinical guidelines can achieve the purpose of leading doctors at all levels in the country to provide standardized treatment for patients, and the construction of lymphoma subspecialties is the main measure
of standardized management.

With the support and assistance of hospital leaders and sister departments, the Cancer Hospital of the University of Chinese Academy of Sciences integrates existing clinical, pathological and nursing resources and gradually establishes a lymphoma subspecialty and multidisciplinary diagnosis and treatment (MDT) team
.
At the same time, the rapid development of innovative drugs, such as the good performance of obinutuzumab in various iNHLs, has enriched the standard treatment regimen of first-line induction therapy, maintenance therapy and recurrence progression of iNHL patients, and accelerated the construction
of lymphoma subspecialties while promoting the progress of standardized management of lymphoma.
In addition, the Cancer Hospital of the University of Chinese Academy of Sciences has also opened the MDT Clinic for Malignant Lymphoma, which is patient-centered and relies on a multidisciplinary team to formulate standardized, individualized and continuous comprehensive treatment plans
for patients with malignant lymphoma.
In the future, we will continue to strengthen the skills of medical, nursing and technical personnel under multidisciplinary cooperation, and hope that the construction of lymphoma subspecialty and full-process management experience in our hospital can provide assistance
for promoting standardized treatment of lymphoma.

Standardized treatment of iNHL can help prolong PFS, improve prognosis, and improve quality of life, but there are still shortcomings
in the clinical treatment of iNHL in China.
Therefore, it is imperative to further promote standardized treatment and improve the level of clinical standardized medication
.
Based on solid evidence-based medical evidence and excellent clinical value, obinutuzumab has been consistently recommended by domestic and foreign guidelines and has become the standard treatment for
FL.
It is believed that under the guidance of guidelines, the standardized use of obinutuzumab can truly help to exert its best clinical efficacy and help standardize
clinical practice in various centers.
In the future, with the continuous improvement of the standardized treatment system of iNHL, China will further strengthen the development of iNHL specialty diseases, multidisciplinary cooperation and the whole health management of lymphoma patients, and witness the continuous emergence of new drugs and new programs in the new era to bring more clinical benefits
to patients.