Follicular lymphoma (FL) is an inert non-Hodgkin’s lymphoma (NHL) that originates from follicular germinal centers, accounting for approximately 20% of all lymphomas, and is second only to diffuse large B-cell lymphoma (DLBCL) in terms of incidence, with a median age of 60 years and a median survival time of more than 10 years. Grade 3 FL should follow the principles of DLBCL treatment, while grade 1~2 are stratified according to patients’ clinical characteristics. With the progress of related clinical trials and the introduction of new drugs, the treatment pattern of FL is gradually changing. 1. Treatment of primary FL 1. Early FL treatment FL mainly involves lymph nodes, also seen in the spleen, bone marrow, peripheral blood and Wechsler’s ring, and occasionally seen in primary extra-nodal sites. Univariate analysis suggested that overall survival (OS) was better in patients with primary cutaneous stage I FL than in patients with primary lymph nodes (HR 0.74, 95% CI 0.63-0.59), while OS was significantly better in patients with primary respiratory (HR 1.69, CI 1.18-2.4), motor (HR 2, CI 1.37-3), and neurological (HR 1.9, CI 1.37-2.68) systems. 2.68) were significantly worse than patients with primary lymph nodes. Multifactorial analysis suggested that only primary epidermis was associated with better OS (HR 0.77, CI 0.66-0.9), while patients with primary nervous system (HR 2.4, CI 1.72-3.38) and motor system (HR 2.14, CI 1.44 ~3.18) had poorer OS, and early aggressive treatment could benefit this group of patients. The use of rituximab (RTX) led to improved OS in early patients with extra-nodal involvement and better survival in patients treated with surgery or radiotherapy. Involved field radiotherapy is recommended by NCCN guidelines for patients with stage I FL. In a retrospective comparison of 1914 patients with stage I FL at St. Joseph Regional Medical Center in the United Kingdom over a 10-year period, the data showed a 1-year OS of 96.1% vs. 100% and a 5-year OS of 89.3% vs. 98.7% in both groups (no combined radiotherapy vs. combined radiotherapy), with significantly longer OS in radiotherapy patients in both the middle-aged and elderly groups. 2. The NCCN guidelines recommend the principle of “watch and wait” (WW) for the management of intermediate to late stage asymptomatic FL. The National Cancer Center Hospital in Japan investigated the effect of WW therapy on FL patients in the RTX era. Of the 348 patients included in the study, 101 received WW after diagnosis and 247 received treatment under physician supervision. 45 patients in the WW group received antitumor therapy for disease progression after a median follow-up of 16 months. the median time to treatment failure (TTF) was 92 and 85 months in the WW and treatment groups, with no significant difference; there was no statistically significant difference in OS rate or cumulative risk of conversion between the two groups. This suggests that WW treatment of FL does not negatively affect TTF, OS or increase the pathological conversion rate regardless of tumor load, indicating that this treatment can still be considered an effective treatment in the RTX era, while the selection of the optimal timing of treatment after WW still needs to be explored in trials. For high-stage low-grade FL, the MD Anderson Center compared the efficacy of both bendamustine combined with RTX (BR) and RTX combined with CHOP (R-CHOP) regimens over the same period, and the results suggested that the complete remission (CR) rates were similar, and the 2-year progression-free survival (PFS) (85% vs 82%) and OS (94% vs 99%) were similar in the BR and R-CHOP groups, yielding high-stage The CR rates for first-line regimens with BR or R-CHOP were similar in patients with low-grade FL. The GAUDI phase Ib maintenance trial is now complete, and preliminary results are available on the comparison of GA101 (Obinutuzumab) in combination with bendamustine and Obinutuzumab in combination with CHOP: 81% and 72% of the 72 participants (36 in each group) completed maintenance therapy, respectively, from the end of induction therapy to the end of maintenance. The CR rate and overall response rate (ORR) improved for both regimens from the end of induction therapy to the end of maintenance therapy, and the PFS at 32 months was 92% and 84%, respectively, suggesting that Obinutuzumab in combination with chemotherapy followed by Obinutuzumab maintenance resulted in a higher CR rate in patients with primary FL, an acceptable probability of side effects such as opportunistic infections, and granulocytopenia with clinical symptoms ( NP) was only found in the Obinutuzumab combined with bendamustine group. The Norris Condon Cancer Center in Lebanon studied the BR regimen in combination with 90YIT for primary FL. 42 patients received 4 courses of BR followed by 6-12 weeks of 90YIT maintenance therapy. The CR (including CRu) rate was 83%, ORR was 96%, and 71% of patients in partial remission (PR) achieved CR/CRu after 90YIT treatment. the BR regimen combined with 90YIT was considered effective and safe as a first-line regimen for primary FL. II. Treatment of high-risk, relapsed/refractory FL 1. Hematopoietic stem cell transplantation Patients with high-risk FL treated with autologous hematopoietic stem cell transplantation (ASCT) can achieve long-term remission, and those who receive transplantation after first remission have a significant advantage in PFS and event-free survival (EFS) over those who receive conventional treatment, but whether OS benefits are inconclusive. In a Spanish multicenter study that included 640 patients receiving ASCT with a post-transplant follow-up of 12.2 years, the statistics showed that median PFS and OS were 9.4 and 21.3 years, respectively. patients transplanted after CR1 had better PFS (68%) and OS (73%), while those transplanted after PR1 were inferior to the former. The results from this center also showed that neither FLIPI I/II had a meaningful prognostic stratification for patients transplanted after CR1. In contrast to other results, the analysis of data from this center suggests that the use of RTX does not improve the survival of patients who underwent ASCT consolidation after CR1. However, it is certain that ASCT is an appropriate option for patients who achieve a better outcome after chemotherapy, and that a proportion of patients can be cured and not relapse even if the initial results suggest a poor prognosis. The results of the Cleveland Clinic study showed that the median PFS of FL relapsed/refractory patients who received ASCT in the RTX years was 49 months, and that increasing age and number of induction treatments were negatively associated with prognosis, so young FL patients with relapsed/refractory disease should receive ASCT as early as possible. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is thought to bring long-term remission in chemotherapy-sensitive relapsed patients. The results of a multicenter phase II clinical trial led by the American Bone Marrow Transplantation Network affirmed the efficacy of combined RTX reduced pretreatment intensity allo-SCT for relapsed FL. 65 patients with salvage therapy-sensitive relapsed FL received pretreatment with a high-dose RTX combined with FC regimen (RTX 1000 mg/m2, -13d, -6d, +1d, and +8d) with a median follow-up of 24 months and 62 The evaluable data showed: 2-year PFS and OS of 75% and 83%, respectively; cumulative incidence of relapse/progression and non-relapse mortality of 10% and 15% at 2 years; and incidence of grade 2-4 and grade 3-4 graft-versus-host disease (GVHD) of 27% and 10%, respectively, of which 55% were extensive chronic GVHD. serum RTX concentrations were still measurable 1 year after transplantation. The results showed that allo-SCT with reduced-intensity pretreatment combined with high-dose RTX resulted in a low relapse/progression rate and significant survival for patients with relapsed FL. 2. New drug therapy (1) Irutinib: The results of a phase II clinical trial of irutinib for relapsed/refractory NHL with multicenter participation in the United States showed that: 40 patients (median age 64 years) enrolled had an ORR of 30% (12 cases; 1 CR, 11 PR), median effective time of 2.4 months, and median PFS of 9.9 months. Only 1 case progressed after 9.9 months of dosing. 4 cases had delayed dosing or dose reduction due to adverse events, including anemia, NP, and infection, and 17 patients dropped out of the group due to disease progression, serious adverse effects, or death, including 3 patients who died due to disease progression, pneumonia, and gastric bleeding, respectively. The results of early evaluation suggest that patients with relapsed/refractory FL can tolerate single-agent irutinib treatment and obtain a general ORR, but the effect of irutinib on FL is not satisfactory compared with that of set cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL). (2) PI3K inhibitors: In an international multicenter study involving PI3K inhibitors for relapsed/refractory NHL and CLL, 16 FL patients received a regimen of Copanlisib 0.8 mg/kg ivd 1d, 8d, 15d; a 28-day course. The results of post-treatment evaluation suggested that 1 case in the FL group obtained CR, 2 CRu, 5 PR, ORR 53%, and PI3K inhibitor was an effective drug for relapsed/refractory FL with acceptable side effects (hyperglycemia, hypertension, weakness, diarrhea, NP, anemia, etc.). (3) Lenalidomide in combination with Obinutuzumab: 20 patients (median age 64 years) were treated with lenalidomide in combination with Obinutuzumab in 6 cycles of 28 days, with patients receiving progressively higher oral doses (10-25 mg) of lenalidomide from 1 to 21 days (2 to 22 days for 2 to 6 cycles) and at 8d, 15d, 22d Obinutuzumab 1000mg was applied intravenously (day 1 only for cycles 2-6). The results of the trial suggest that patients with relapsed/refractory FL can tolerate oral lenalidomide combined with Obinutuzumab regimen with good efficacy at the recommended lenalidomide dose of 20 mg each. Further trials are continuing. In addition to the new drugs mentioned above, clinical trials such as oral clofarabine, CD79b monoclonal antibody and CD22 monoclonal antibody, and IFNa2b in combination with COP regimens have been conducted for the treatment of relapsed/refractory FL with varying degrees of results, and further exploration is actively underway. Third, the treatment of FL with transformation FL to DLBCL, the degree of tumor aggressiveness is greatly increased, and the prognosis of patients is not satisfactory. In a retrospective analysis of 56 patients at the Royal Marsden Hospital, the 2-year and 5-year OS of patients who had received RTX combined with chemotherapy before transplantation were 84.5% and 70.9%, respectively, which were better than those who underwent direct ASCT, and the PFS was also more favorable, while the treatment caused less toxic side effects, so the center believes that RTX chronological priority transplantation may no longer be the only option for transformed FL, and RTX maintenance may be considered for the treatment of this group of patients. The value of PET-CT in the management of FL has been controversial except for guiding biopsies and detecting transformed lesions.High SUVmax in PET-CT reports often suggest the possibility of highly aggressive FL lesions and transformation to DLBCL, but the correlation between high SUVmax values and patient prognosis is unknown.A related study was conducted at the MD Anderson Center In a study conducted at the MD Anderson Center, 225 patients with stage III/IV FL treated with the R-CHOP regimen (excluding transformed patients) were divided into two groups according to baseline PET-CT SUVmax ≤13 (105 patients) and >13 (120 patients), with no significant differences in patient characteristics including age, gender, pathological grade, Ki-67 level and FLIPI score between the two groups; after a median follow-up of 66 months, ORR and CR were 96. After a median follow-up of 66 months, ORR and CR were 96% and 87%, with no significant differences in 5-year PFS and OS. The investigators further grouped GELF criteria-positive patients by SUVmax, and the statistical results showed that PFS and OS remained indistinguishable, suggesting that SUVmax values of baseline PET in patients with stage III/IV FL treated with R-CHOP cannot be used as a prognostic factor.