[ICML Review] Professor Xu Bing commented on the FOLL12 study: After the induction therapy of FL patients, can the maintenance treatment plan of rituximab be adjusted according to the efficacy?

After the induction therapy of patients with follicular lymphoma (FL) is finished, can the maintenance treatment plan of rituximab be adjusted according to the efficacy of induction therapy? This is a clinical issue that deserves attention
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The relevant results of the FOLL12 study at this ICML conference were selected as oral reports.
Professor Lin Zhijuan from the Department of Hematology, the First Affiliated Hospital of Xiamen University was specially invited to compile and Professor Xu Bing to comment on this study, and to take everyone to understand the importance of maintenance treatment for FL patients
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01 Research background After rituximab-based first-line immunochemotherapy, two-year rituximab maintenance (RM) can significantly improve the progression-free survival (PFS) rate of FL patients
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However, whether all FL patients are suitable for the above maintenance treatment plan
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The researchers designed the FOLL12 study to explore the best maintenance treatment plan by comparing the impact of the standard maintenance treatment plan with the selection of the maintenance treatment plan based on the efficacy on the survival of FL patients
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02 Research methods The study enrolled FL patients with newly diagnosed, advanced, and high tumor burden, and randomly divided into experimental group and control group.
Patients in the experimental group selected maintenance treatment options based on the therapeutic efficacy (including metabolic response and minimal residual disease status) after induction therapy , While patients in the control group received the standard regimen of rituximab maintenance
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The end of induction therapy (EOI) complete metabolic remission (CMR) is defined as the DS 1-3 score of the PET-CT DS score (Deauville scale) 5-point method
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Minor residual disease (MRD) negative is defined as positive Bcl2/IgH rearrangement at baseline, and the bone marrow and peripheral blood Bcl2/IgH rearrangement becomes negative after induction therapy.

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The treatment plan for the experimental group after induction is: CMR and MRD- patients, observe; CMR and MRD+ (EOI or follow-up) once every 4 weeks with rituximab until at least 3 courses of MRD-; patients without CMR, one dose of ibritumomab Sequential standard RM after tiuxetan
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The main study endpoint is the 3-year PFS rate
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The results of the 03 study among 807 randomized patients, 712 achieved ≥ partial remission (PR) efficacy at EOI
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After a median follow-up of 53 (1-92) months, the PFS of the control group was significantly better than that of the test group (3-year PFS rates were 86% and 72%, respectively, P<0.
001)
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The subgroup study also confirmed that the PFS of the control group was significantly better than that of the test group (Figure 1); CMR patients (A) (N=628) The 3-year PFS rates of the control group and the test group were 90% and 72%, respectively (P< 0.
001); CMR simultaneous MRD-patients (B) (N=299) were 92% and 78% (P<0.
001); CMR simultaneous MRD+ patients (C) (N=46) were 96% and 45% (p =0.
004)
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Among the 65 patients without CMR (D), there was no difference in the 3-year PFS rate between the control group and the test group (P=0.
274)
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At the time of the latest data update, 30 deaths were reported, 15 of which were related to disease progression or recurrence
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The 3-year overall survival (OS) rates of the control group and the experimental group were 98% (95%CI 96-99) and 97% (95%CI 95-99) (p=0.
238), respectively
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Figure 104 Study conclusions The FOLL12 study suggests that compared with the standard 2-year rituximab maintenance treatment, choosing the rituximab maintenance treatment based on the efficacy will lead to a significant decrease in the PFS of the patient
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Even if patients get CMR and MRD- at the end of induction therapy, they can benefit further from standard maintenance therapy
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Professor Xu Bing commented that FL is a common indolent lymphoma.
The incidence of FL in European and American countries accounts for 20%-30% of B-cell non-Hodgkin's lymphoma (B-NHL).
The incidence of FL in China is lower than that in European and American countries.
However, the incidence rate is still relatively high in developed coastal areas
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More than 80% of FL patients are diagnosed in advanced stages.
At present, advanced FL cannot be cured.
Most patients will experience several relapses and multi-line treatments.
As the number of treatment lines increases, the remission rate gradually decreases and the remission period gradually shortens.
The toxicity of treatment will gradually increase
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In addition, FL is very heterogeneous, and the main challenge of FL treatment at present is disease transformation and early disease progression (POD24)
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Therefore, the goal of advanced FL treatment is to delay disease progression, improve disease-free survival and quality of life, and avoid early recurrence and transformation
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The ECOG1496 study is the first phase III clinical study to reveal that rituximab maintenance therapy can benefit FL patients: the median PFS of the rituximab maintenance treatment group and the unmaintained group were 4.
2 years and 1.
5 years, respectively, and 3-year OS The rates are 91% and 86% respectively
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Another large randomized phase III controlled study, PRIMA, enrolled 1217 patients.
The study was followed up for 10 years.
The PFS of the rituximab maintenance treatment group was significantly longer than that of the unmaintained group (10.
5 years vs 4.
1 years, P<0.
0001).
51% of patients in the rituximab maintenance group did not progress for 10 years (only 35% in the unmaintained group)
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The ARISTOTLE study retrospectively assessed the risk of FL histological transformation in the immunochemotherapy era.
A total of 8116 patients were enrolled.
The 10-year risk of disease transformation in the rituximab-only induction therapy group vs.
induction plus maintenance therapy group was 5.
9% and 3.
6%, respectively.
It is suggested that the first-line maintenance treatment with rituximab may reduce the risk of disease transformation
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The FOLL12 study reported at the ICML conference once again confirmed the importance of FL maintenance therapy.
Even if the patient's induction therapy is over, FL patients who obtain CMR and MRD- can still benefit from rituximab maintenance therapy for 2 years
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Professor Xu Bing, a second-level chief physician, professor, and doctoral supervisor, Director of the Department of Hematology, Xiamen University, Director of the Department of Hematology, Xiamen University, Director of the First Affiliated Hospital of Xiamen University, Director of the Department of Hematology and Director of the Department of Internal Medicine, Director of the Internal Medicine Training Base, Leader of the Chinese Follicular Lymphoma Working Group, Chairman of the Leukemia Academic Working Committee of the Chinese Society of Geriatrics, Member of the Standing Committee of the Hematology and Tumor Professional Committee of the Chinese Anti-Cancer Association 1 prize, 3 second prizes, presided over 4 National Natural Science Foundation of China, published more than 200 papers as the first or corresponding author, including 60 SCI papers, 20 papers with a score of 5 or more, and a total impact factor of more than 200.
Professor Lin Zhijuan Doctor of Hematology, Department of Hematology, The First Affiliated Hospital of Xiamen University, Associate Chief Physician Graduated from Peking University Clinical Medicine for eight years.
Visiting scholar, Cleveland Medical Center, United States.
Youth Committee of the Lymphoma Professional Committee of Fujian Anti-Cancer Association Reference: 16-ICML, 2021, Oral presentation 080.
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