2021 CSCO Innovation Prospects Prof. Wei Zhang Analyzes the "Breakthrough" of Otuzumab in the Treatment of Indolent Lymphoma

Indolent B-cell lymphoma is a more common type of chronic lymphoma.
Although indolent B-cell lymphoma develops slowly and the patient survives longer, indolent B-cell lymphoma usually cannot be completely cured
.

In recent years, the treatment of indolent B-cell lymphoma has gradually shifted from the optimization of treatment plans to the optimization of therapeutic drugs
.

New drugs led by a new generation of anti-CD20 monoclonal antibody otuzumab have shown better curative effects in indolent B-cell lymphoma, bringing more benefits to patients
.

On September 25-29, 2021, the 24th National Conference on Clinical Oncology and the 2021 CSCO Academic Annual Conference were officially held.
The theme of the conference was "Focus on Innovative Research, Leading the Future of Originality", which reflects CSCO's support for innovative drugs
.

During the conference, Yimaitong was fortunate to invite Professor Zhang Wei from Peking Union Medical College Hospital to accept an interview to share clinical experience and talk about the changes that Otuzumab has brought to the treatment strategy of indolent B-cell lymphoma
.

Yimaitong: First of all, could you please introduce the current dilemma in the treatment of indolent B-cell lymphoma, and what are the current development directions for the treatment of indolent B-cell lymphoma? Professor Zhang Wei has a lower incidence of indolent lymphoma in China than in European and American countries.
However, with the popularization of medical examinations and the development of an aging society, the number of confirmed cases of indolent lymphoma in major centers has increased significantly in recent years
.

Indolent lymphoma, as its name suggests, is a type of lymphoma with slow disease progression.
However, even in the era of new drugs, indolent lymphoma is still an incurable disease, and patients will relapse repeatedly during the course of the disease
.

Despite this, clinicians still hope to improve the quality of life of patients with lazy lymphatics and reduce recurrence, so that patients can survive with tumors and achieve the same life span as their peers.

.

In addition, some patients with lazy lymphoma have disease progression (POD24) within two years after starting immunochemotherapy.
The prognosis of this part of patients is similar to that of aggressive diffuse large B-cell lymphoma (DLBCL), and long-term tumor-carrying survival cannot be achieved.
It is currently clinical The more difficult issues in
.

In recent years, the treatment of Laidlin has progressed rapidly, and new drugs represented by the new generation of anti-CD20 monoclonal antibody otuzumab have shown excellent efficacy and safety
.

We hope that with the emergence of many new drugs, there will be better treatments to reduce the occurrence of POD24 and solve this clinical "rigorous need"
.

Yimaitong: At present, a number of clinical trials have explored the application of otuzumab in indolent B-cell lymphoma.
Could you please briefly introduce the research progress of otuzumab in indolent B-cell lymphoma? ? What changes have these research results brought to the treatment strategy of indolent B-cell lymphoma? Professor Zhang Wei rituximab was launched in China in 2000, which we all call a "milestone"
.

However, after more than two decades, rituximab has limited efficacy in chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), DLBCL and other lymphomas
.

Jalova® (Otuzumab) is a long-awaited new humanized anti-CD20 monoclonal antibody for our doctors and patients, which breaks the bottleneck of rituximab's curative effect
.

Therefore, in recent years, the NCCN guidelines and ESMO guidelines have basically changed the recommended CD20 monoclonal antibody for the treatment of B-cell lymphoma from rituximab to otuzumab
.

In the initial treatment of FL, the GALLIUM study compared the efficacy of otuzumab (G) combined with chemotherapy and traditional rituximab (R) combined with chemotherapy
.

The results of the study showed that compared with rituximab combined with chemotherapy, otuzumab combined with chemotherapy significantly prolonged the PFS of newly treated FL patients (3-year PFS rate: 80.
0% vs 73.
3%; 95% CI: 0.
51 -0.
85; P=0.
001), while reducing the risk of disease progression, recurrence and death by 34%, reducing the risk of POD24 by 46%, and extending the time to next treatment (TTNT) by 28%
.

Otuzumab combined with chemotherapy can also bring more profound disease relief to FL patients.
FL patients receiving Otuzumab combined with chemotherapy have a higher negative rate of minimal residual disease (MRD) (94.
3% vs 88.
9) %; P=0.
013)
.

Based on this, the FDA quickly approved the combination of otuzumab and chemotherapy for the treatment of newly-treated FL.
At present, G-chemotherapy has become the new standard for first-line treatment of FL
.

In relapsed and refractory FL, the combination of otuzumab also showed good efficacy and safety
.

The GADOLIN study showed that compared with bendamustine single-agent regimen, otuzumab combined with bendamustine regimen can significantly improve the PFS and overall survival (OS) of patients with relapsed and refractory FL, and there is no unexpected Security incidents
.

Many previous studies of rituximab have found it difficult to improve the OS of relapsed and refractory FL.
However, the combination of otuzumab and bendamustine, plus maintenance treatment of otuzumab, can be seen after 3 years of follow-up.
A statistically significant improvement in OS is very rare
.

Otuzumab is also a drug that cannot be ignored in the treatment of CLL.
The results of the CLL11 study show that compared with rituximab, the efficacy of otuzumab combined with chlorambucil in the treatment of CLL is significantly better, with a median PFS is longer (31.
1 months vs 11.
1 months)
.

Therefore, as early as 2013, otuzumab was approved by the FDA for the first-line treatment of CLL based on the results of the CLL11 study
.

Afterwards, the CLL14 study explored the efficacy and safety of a fixed course of venexaline combined with otuzumab (VenG) and chlorambucil combined with otuzumab (ClbG) in newly-treated CLL patients with comorbidities.
Sex
.

The results of the study show that the VenG regimen is safe in CLL patients, PFS benefits more (4-year PFS rate: 74.
0% vs 35.
4%), and the MRD negative rate is higher (MRD negative rate 30 months after the completion of treatment: 26.
9% vs 3.
2%)
.

The latest results of the CLL14 study undoubtedly provide a new "chemo-free" treatment option for CLL patients, greatly increasing the chances of prolonging survival and improving the quality of life of patients, and making it possible to stop the drug
.

In marginal zone lymphoma (MZL), the LYSA Phase II clinical study explored the efficacy and safety of otuzumab+venecla+atilizumab in the treatment of R/R FL/MZL.
The study was included in the group In 20 patients with MZL, the total effective rate of CT evaluation at the end of 8 cycles of treatment was 66.
76% (CR rate 16.
7%, PR rate 50.
0%)
.

The efficacy of the triple regimen in the R/R FL/MZL cohort was relatively long-lasting.
During the follow-up, only 21.
4% of remission patients reported recurrence/progress
.

The median age of onset of mantle cell lymphoma (MCL) patients is 60-65 years old.
Therefore, in clinical practice, we are more pursuing "no chemotherapy" programs with less side effects
.

The phase I/II prospective OASIS study explored the efficacy of ibrutinib, otuzumab combined with venacral in MCL
.

The results of the current study show that: patients with recurrent mantle cell lymphoma were followed up for a median of 17 months, and the estimated 2-year PFS rate and OS rate reached 69.
5% and 68.
6%, respectively; the median follow-up of patients with newly diagnosed mantle cell lymphoma was 14 months, 1 The annual PFS rate and OS rate are 93.
3% and 100%, respectively
.

The combined regimen is well tolerated and can provide a higher remission rate for mantle cell lymphoma, and its further research results are very worth looking forward to
.

Yimaitong: At present, otuzumab has been commercialized in China.
Could you please share your clinical experience and experience? After Professor Zhang Wei's otuzumab was launched in China, the cost of one cycle of treatment was lower than the clinician's expectations.
It is conceivable that the clinical accessibility after the market was better than expected
.

At present, our department has three initial patients with FL who have been treated with otuzumab, all between the ages of 60-70
.

All three patients have indications for treatment.
One patient has waited for observation for 4 years and now has digestive tract symptoms such as weight loss and intestinal involvement.
The other two patients are newly treated patients with advanced stages with huge masses and systemic symptoms
.

All three patients were treated with otuzumab combined with bendamustine, and the efficacy has not been evaluated yet
.

In the process of clinical medication, my biggest experience is the good safety of otuzumab.
Past experience suggests that 20%-30% of patients will have allergic reactions during the first infusion of rituximab, but use None of the three patients with otuzumab had allergic reactions
.

At present, the three patients are in good physical condition, and I believe that they will get better results in the mid-term evaluation
.

Yimaitong: Given the excellent efficacy and safety of otuzumab in related research and clinical practice, what prospects do you have for the application of otuzumab in indolent B-cell lymphoma? Professor Zhang Wei just mentioned CLL.
The first choice for the treatment of CLL is BTK inhibitors, but there will be a "shift" phenomenon during the initial treatment of BTK inhibitors, that is, a sharp increase in white blood cells.
The clinical need to add CD20 monoclonal antibody to reduce the increase in white blood cells.
Adverse reactions
.

In addition, CLL patients also hope to pursue limited-period treatment to improve their quality of life
.

Based on this, otuzumab has become the best choice for combination therapy
.

In addition, no chemotherapy is currently a hot topic in cancer treatment.
CLL, MCL, and FL patients are older and require less toxic treatments
.

The results of the Phase II clinical study of otuzumab combined with lenalidomide (GLen) regimen in the treatment of newly-treated FL were surprising.
The 2-year PFS rate was as high as 96%; the median follow-up was 25 months, and the complete remission rate was as high as 94%.
The overall remission rate reached 96%, and the GLen-free chemotherapy regimen has more advantages than traditional chemotherapy regimens in terms of safety
.

The current efficacy data of the study is better than the previous data of rituximab combined with lenalidomide (R2 regimen), and the results of the extended follow-up study are very worth looking forward to
.

At present, GLen has been listed in the NCCN guidelines and CSCO guidelines as the first-line treatment recommendation for FL
.
The chemotherapy-free regimen based on otuzumab is expected to become the new standard for the first-line treatment of FL .

At present, the first indication for otuzumab approved in China is follicular lymphoma.
In the future, otuzumab will gradually replace rituximab as the cornerstone of lymphoma treatment
.

I hope that more indications can be approved in China, and that otuzumab can enter the medical insurance as soon as possible, improve the accessibility of clinical drugs, and allow more patients to obtain better quality of life and longer survival
.

Zhang Wei Chief Physician, Master's Tutor, Youth Committee of Chinese Society of Geriatric Lymphoma, Committee of Hematology and Oncology, Chinese Society of Anti-Cancer Society, Committee of Hematology and Immunology Branch of Chinese Society of Immunology, Member of Standing Committee of China Anti-Lymphoma Alliance, Secretary of Expert Committee of Hematology, Beijing Medical Awards Foundation ★ Scan below 2 Dimension code, enter the "Mystery Exploration" channel★Poke "Read the original text" and enter the "Mystery Exploration" channel!