Professor Zhang Huilai talks about the treatment of follicular lymphoma: Otuzumab significantly reduces the risk of POD24 and brings better prognosis

Follicular lymphoma is one of the common indolent lymphomas, currently incurable and prone to recurrence
.

For high-risk newly treated patients, prevention of early recurrence is particularly important
.

If a patient develops disease progression (POD24) within 24 months after starting first-line immunochemotherapy, the risk of death will be greatly increased.
Therefore, how to choose the preferred treatment drug and reduce the risk of POD24 has become an important goal of FL treatment
.

 The humanized glycosylated type II anti-CD20 monoclonal antibody-Otuzumab was approved in China in June this year and used in combination with chemotherapy for the first-line induction therapy of newly-treated adult patients with follicular lymphoma (FL) After achieving at least partial remission, the monotherapy of Otuzumab maintenance therapy will bring new hope for meeting the treatment needs of Chinese FL patients
.

Yimaitong specially invited Professor Zhang Huilai, director of the Lymphatic Oncology Department of Tianjin Medical University Cancer Hospital to share clinical experience with you
.

Case profile: The patient was 59 years old and was pathologically diagnosed as grade 1 follicular lymphoma, with a FLIPI2 score of 3 (high risk), and Ann Arbor stage IV
.

The requirements for the initial treatment effect are high, and it is hoped to reduce the risk of recurrence and early progression
.

Case discussion and plan selection During the entire course of FL, most patients will have multiple recurrences, and the difficulty of treatment will increase after each relapse, especially for patients with POD24.
The results of multiple clinical studies have confirmed the overall survival of this part of patients.
(OS) and OS rates are significantly worse [1]
.

 The results of a clinical study involving 588 newly treated FL patients showed that 19% of patients had POD24 after receiving the current standard first-line treatment (R-CHOP regimen).
The 5-year OS rate of this part of patients was 50%, and no POD24 occurred.
The 5-year OS rate of patients is 90% (Figure 1) [2]
.

The relative risk of death of patients with POD24 is 12 times that of patients without POD24 (HR=12.
2) [3]
.

Figure 1 OS rate of patients receiving R-CHOP treatment (POD24 vs.
no POD24) It can be seen that reducing the occurrence of POD24 events is of great significance for reducing the risk of death after progression of FL patients and improving the prognosis
.

 A total of 1202 patients were enrolled in the GALLIUM study to evaluate the efficacy of otuzumab combined with chemotherapy (G-chemo) compared with the existing standard treatment (R-chemo) for the first-line treatment of FL
.

The latest 5-year follow-up results showed that the risk of POD24 in the G-chemo group was 47.
6% lower than that in the R-chemo group (95%CI: 27.
1-62.
4)
.

[4] The proportion of POD24 patients in the R-chemo group was 16.
3%, and that in the G-chemo group was 9.
2% (Figure 2)
.

The progression-free survival (PFS) of patients in the G-chemo group was prolonged (5-year PFS rate: 70.
5% vs 63.
2%), and the time to next anti-lymphoma treatment (TTNALT) was also improved (79.
7% vs 72.
9%)
.

Figure 2 The proportion of POD24 patients in the GALLIUM study.
Considering that the patient's FLIPI2 score of 3 is classified as high-risk, through comprehensive considerations in clinical practice, under the premise of protecting the patient's bone marrow function and ensuring the long-term feasibility of follow-up treatment, when the priority is given to treatments that can reduce the risk of POD24 Scheme
.

Based on the results of the GALLIUM study, after comprehensively assessing the patient's disease type, stage, and prognostic stratification and other factors, the combination treatment plan based on otuzumab became its treatment plan
.

Experts’ message: “FL is a highly heterogeneous disease.
The results of a meta-analysis of POD24 risk factors for FL patients in Tianjin Medical University Cancer Hospital showed that sIL-2R increased, TMTV> 510mL, β2m increased, LDH increased, Pathological grade 3a, lymphoma-related macrophages/high power field (LAM/HPF) ≥15, vitamin D deficiency is significantly associated with increased risk of POD24
.

At present, prognostic scores such as FLIPI, FLIPI2, m7-FLIPI, and POD24-PI are used in clinical practice The system stratifies the prognosis of patients, but the existing scoring system cannot completely accurately predict the occurrence of POD24, so choosing the optimal treatment plan to reduce the risk of early progression is an important goal for the treatment of FL
.

According to the results of the GALLIUM study, Compared with low- and medium-risk patients, POD24 events are more common in patients with high-risk FLIPI scores, which also has certain reference significance for clinical treatment
.

 This time the patient’s FLIPI2 score is 3 points, and the risk of POD24 is higher in patients.
Young and hoping to get a better prognosis and reduce the risk of recurrence, after a comprehensive assessment, a combination treatment plan based on otuzumab was selected for the patient, hoping to reduce the risk of POD24, prolong PFS, and improve the patient's quality of life
.

 At present, otuzumab has been approved and put into clinical application in China, bringing new first-line treatment options to more FL patients
.

In addition, otuzumab combined with lenalidomide (GLen) regimen has also made great progress in the treatment of newly treated FL.
The results of a phase II clinical study showed that at a median follow-up of 25 months, the complete remission rate was as high as 94%, and the total remission rate To reach 96%, the 2-year PFS rate is as high as 96%, and only 4% of patients have POD24, which can effectively reduce the risk of POD24 in FL patients, and the GLen-free chemotherapy regimen has more advantages than traditional chemotherapy regimens in terms of safety [5]
.

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

"Professor Zhang Huilai, Doctor of Oncology, Chief Physician, and Doctoral Supervisor.
Currently, Director of the Department of Lymphoma, Tianjin Medical University Cancer Hospital, Deputy Chairman of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association, Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Anti-Lymphoma Alliance China Medical Vice Chairman of the Oncology Branch of the Health Care International Exchange Promotion Association Vice Chairman of the Lymphoma Professional Committee of the Chinese Geriatric Healthcare Association Member of the Standing Committee of the Chinese Society of Clinical Oncology (CSCO) Oncology and Cardiology Committee Member of the Lymphoma Group of the Oncology Branch of the Chinese Medical Association Chinese Anticancer Member of the Association Integrated Oncology and Cardiology Committee Member of the Lymphoma Professional Committee of Tianjin Anti-Cancer Association Vice Chairman of Tianjin Blood Disease Quality Control Center Vice Chairman of Tianjin Medical Doctor Association Hematologist Branch Reference: [1] Maurer MJ, Bachy E, Ghesquières H, et al.
Early event status informs subsequentoutcome in newly diagnosed follicular lymphoma.
American Journal of Hematology.
2016 Nov;91(11):1096-1101.
[2]Casulo C, Byrtek M, Dawson KL, et al.
Early Relapse of Follicular LymphomaAfter Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and PrednisoneDefines Patients at High Risk for Death: An Analysis From the NationalLymphoCare Study.
Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology.
2015 Aug;33( 23):2516-2522.
[3]SeymourJF, Marcus R, Davies A, et al.
Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression.
Haematologica.
2019,104(6): 1202-1208.
[4]William Townsend, et al.
ASCO 2020 .
#P8023.
[5] Nastoupil LJ et al.
Resultsof a phase II study of obinutuzumab in combination with lenalidomide inpreviously untreated, high tumor burden follicular lymphoma (FL); 2019 Dec 7.
Oral Abstract #125: 61st American Society of Hematology ( ASH) Meeting &Exposition, Orlando, US.
★ Scan the QR code below to enter the "Mystery Exploration" channel ★Poke "Read the original text" to enter the "Mystery Exploration" channel!Resultsof a phase II study of obinutuzumab in combination with lenalidomide inpreviously untreated, high tumor burden follicular lymphoma (FL); 2019 Dec 7.
Oral Abstract #125: 61st American Society of Hematology (ASH) Meeting &Exposition, Orlando, US.
Scan below QR code to enter the "Mystery Exploration" channel★Poke "Read the original text" to enter the "Mystery Exploration" channel!Results of a phase II study of obinutuzumab in combination with lenalidomide inpreviously untreated, high tumor burden follicular lymphoma (FL); 2019 Dec 7.
Oral Abstract #125: 61st American Society of Hematology (ASH) Meeting &Exposition, Orlando, US.
Scan below QR code to enter the "Mystery Exploration" channel★Poke "Read the original text" to enter the "Mystery Exploration" channel!