Analyzing the risk factors for disease progression within 2 years and histological transformation in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as first-line treatment: A 15-year follow-up of patients with advanced follicular lymphoma in JCOG0203.

Follicular lymphoma (FL) is an indolent lymphoma that becomes aggressive due to histological transformation (HT), leading to reduced survival. Patients with FL have different clinical courses and various treatment options. Some patients exhibit shorter survival and experience disease progression within 24 months of diagnosis/treatment (POD24); the optimal treatment remains an unmet needs. Thus, identifying factors that predict shorter survival is essential to stratify treatment and prolong the survival of patients with FL. To analyze risk factors for POD24 and HT in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment, we performed this post-hoc analysis of patients with advanced indolent B-cell lymphoma in a randomized clinical trial wherein six cycles of R-CHOP were administered every 2-3 weeks. The primary analysis showed no differences in outcomes, which enabled the analysis of 248 patients with FL, assigned to two arms. All histopathological specimens from the 300 enrolled patients were reviewed by three expert hematopathologists. Multivariable analysis implicated Follicular Lymphoma International Prognostic Index (FLIPI) intermediate (odds ratio [OR] 2.531, 95% confidence interval [CI] 0.676-9.466) and high- (OR 2.236, 95% CI 0.160-31.226) risks, B symptoms (OR 2.091, 95% CI 0.747-5.851), and grade 3A (G3A) (OR 1.833, 95% CI 0.634-5.299) as risk factors for POD24. Furthermore, multivariable analysis through a median follow-up of 15.9 years implicated G3A (OR 2.628, 95% CI 0.806-8.575) and high-risk FLIPI (OR 4.401, 95% CI 0.186-104.377) as risk factors for HT. However, an analysis limited to the first 10 years revealed that the prognostic factors elucidated from the longer-term analysis had a greater impact on HT. G3A and high-risk FLIPI may independently predict POD24 and HT, thereby informing treatment stratification of patients with untreated advanced-stage FL in future trials, particularly to address the unmet needs of patients with POD24.

Phase II study of novel orally PI3Kα/δ inhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma.

This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3-93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases.

AIMS: MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. METHODS: MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. RESULTS: MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). CONCLUSIONS: MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study.

BACKGROUND: Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t-DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t-DLBCL and primary DLBCL (p-DLBCL) in the same timeframe. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p-DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t-DLBCL. RESULTS: Finally, we identified 50,332 FL and 95,933 p-DLBCL. With a median follow-up of 119 months, 1631 patients developed t-DLBCL. The median time from FL diagnosis to t-DLBCL was approximately 4 years. The post-transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t-DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t-DLBCL and p-DLBCL as a whole, comparable survival was observed between p-DLBCL and t-DLBCL receiving radiation or watch-and-wait as initial therapy prior to HT. CONCLUSION: The outcome of t-DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t-DLBCL receiving watch-and-wait or radiation as initial therapy before HT.

Prognostic value of the combination of volume, massiveness and fragmentation parameters measured on baseline FDG pet in high-burden follicular lymphoma.

The prognostic value of radiomic quantitative features measured on pre-treatment 18F-FDG PET/CT was investigated in patients with follicular lymphoma (FL). We conducted a retrospective study of 126 FL patients (grade 1-3a) diagnosed between 2006 and 2020. A dozen of PET/CT-derived features were extracted via a software (Oncometer3D) from baseline 18F-FDG PET/CT images. The receiver operating characteristic (ROC) curve, Kaplan-Meier method and Cox analysis were used to assess the prognostic factors for progression of disease within 24 months (POD24) and progression-free survival at 24 months. Four different clusters were identified among the twelve PET parameters analyzed: activity, tumor burden, fragmentation-massiveness and dispersion. On ROC analyses, TMTV, the total metabolic tumor volume, had the highest AUC (0.734) followed by medPCD, the median distance between the centroid of the tumors and their periphery (AUC: 0.733). Patients with high TMTV (HR = 4.341; p < 0.001), high Tumor Volume Surface Ratio (TVSR) (HR = 3.204; p < 0.003) and high medPCD (HR = 4.507; p < 0.001) had significantly worse prognosis in both Kaplan-Meier and Cox univariate analyses. Furthermore, a synergistic effect was observed in Kaplan-Meier and Cox analyses combining these three PET/CT-derived parameters (HR = 12.562; p < 0.001). Having two or three high parameters among TMTV, TVSR and medPCD was able to predict POD24 status with a specificity of 68% and a sensitivity of 75%. TMTV, TVSR and baseline medPCD are strong prognostic factors in FL and their combination better predicts disease prognosis.

[Studies on clinicopathological features of duodenal-type follicular lymphoma of 18 patients].

To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.

Multi-omic profiling of follicular lymphoma reveals changes in tissue architecture and enhanced stromal remodeling in high-risk patients.

Follicular lymphoma (FL) is a generally incurable malignancy that evolves from developmentally blocked germinal center (GC) B cells. To promote survival and immune escape, tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment. Dynamic interactions between tumor B cells and the tumor microenvironment (TME) are hypothesized to contribute to the broad spectrum of clinical behaviors observed among FL patients. Despite the urgent need, existing clinical tools do not reliably predict disease behavior. Using a multi-modal strategy, we examined cell-intrinsic and -extrinsic factors governing progression and therapeutic outcomes in FL patients enrolled onto a prospective clinical trial. By leveraging the strengths of each platform, we identify several tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse, the most high-risk FL patients. These features include stromal desmoplasia and changes to the follicular growth pattern present 20 months before first progression and first relapse.

Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial.

BACKGROUND: Relapsed or refractory follicular lymphoma (rrFL) is an incurable disease associated with shorter remissions and survival after each line of standard therapy. Many promising novel, chemotherapy-free therapies are in development, but few are licensed as their role in current treatment pathways is poorly defined. METHODS: The REFRACT trial is an investigator-initiated, UK National Cancer Research Institute, open-label, multi-centre, randomised phase II platform trial aimed at accelerating clinical development of novel therapies by addressing evidence gaps. The first of the three sequential novel therapy arms is epcoritamab plus lenalidomide, to be compared with investigator choice standard therapy (ICT). Patients aged 18 years or older with biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma and assessable disease by PET-CT are eligible. The primary outcome is complete metabolic response by PET-CT at 24 weeks using the Deauville 5-point scale and Lugano 2014 criteria. Secondary outcomes include overall metabolic response, progression-free survival, overall survival, duration of response, and quality of life assessed by EQ-5D-5 L and FACT-Lym. The trial employs an innovative Bayesian design with a target sample size of 284 patients: 95 in the ICT arm and 189 in the novel therapy arms. DISCUSSION: Whilst there are many promising novel drugs in early clinical development for rrFL, understanding the relative efficacy and safety of these agents, and their place in modern treatment pathways, is limited by a lack of randomised trials and dearth of published outcomes for standard regimens to act as historic controls. Therefore, the aim of REFRACT is to provide an efficient platform to evaluate novel agents against standard therapies for rrFL. The adaptive Bayesian power prior methodology design will minimise patient numbers and accelerate trial delivery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05848765; 08-May-2023. EUDRACT: 2022-000677-75; 10-Feb-2022.

[A case of follicular lymphoma with recurrent fever and pulmonary infiltrates].

We reported a case of a 65-year-old male who had been treated with obinutuzumab and chemotherapy for follicular lymphoma. He was infected with SARS-CoV-2 after the second course of therapy. He developed fever, cough and bilateral pulmonary infiltrates. His nasopharyngeal swab became negative only temporarily after repeated courses of antiviral therapy, and the symptoms and pulmonary infiltrates waxed and waned. He presented to our hospital with exertional dyspnea and hypoxemia after his nasopharyngeal swab was positive for SARS-CoV-2 for the fourth time. He had an elevated serum lactate dehydrogenase and a positive 1, 3-ß-D-glucan test. The PCR test for Pneumocystis jirovecii in the sputum was positive. The patient was diagnosed with persistent COVID-19 and Pneumocystis jirovecii pneumonia. He responded well to the combination treatment of antiviral medication, convalescent plasma, trimethoprim-sulfamethoxazole and corticosteroids.

Primary pancreatic lymphoma: Histopathological pattern of 8 cases.

OBJECTIVES: To report the histopathological pattern of primary pancreatic lymphoma (PPL) in 2 tertiary hospitals. METHODS: The pathology slides and reports of all the cases diagnosed in pathology departments in 2 referral hospitals were reviewed. An additional immunohistochemistry study was done to reclassify lymphomas according to the current system. RESULTS: Eight patients with PPL have been identified. The ages ranged from 36 to 71 years. Clinical presentation includes abdominal pain, weight loss, jaundice, abdominal mass, nausea, and vomiting. Pathological evaluation revealed 5 diffuse large B-cell lymphomas, one high-grade B-cell lymphoma, one MALT lymphoma, and one follicular lymphoma. CONCLUSION: Primary pancreatic lymphoma is a very rare tumor without specific clinical, laboratory tests, or radiological findings. Abdominal pain is the most common clinical presentation. Diffuse large b-cell lymphoma is the most common pathological subtype. Primary pancreatic lymphoma should be taken into consideration when evaluating pancreatic mass to avoid unnecessary surgical resection.

Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: Results from a bidirectional two-sample two-step Mendelian randomisation.

BACKGROUND: Non-Hodgkin's lymphoma incidence rates vary between European and Asian populations. The reasons remain unclear. This two-sample two-step Mendelian randomisation (MR) study aimed to investigate the causal relationship between anthropometric indicators (AIs) and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and the possible mediating role of basal metabolic rate (BMR) in Europe. METHODS: We used the following AIs as exposures: body mass index (BMI), whole-body fat mass (WBFM), whole-body fat-free mass (WBFFM), waist circumference(WC), hip circumference(HC), standing height (SH), and weight(Wt). DLBCL and FL represented the outcomes, and BMR was a mediator. A two-sample MR analysis was performed to examine the association between AIs and DLBCL and FL onset. We performed reverse-MR analysis to determine whether DLBCL and FL interfered with the AIs. A two-step MR analysis was performed to determine whether BMR mediated the causality. FINDINGS: WBFFM and SH had causal relationships with FL. A causal association between AIs and DLBCL was not observed. Reverse-MR analysis indicated the causal relationships were not bidirectional. Two-step MR suggested BMR may mediate the causal effect of WBFFM and SH on FL. CONCLUSIONS: We observed a causal relationship between WBFFM and SH and the onset of FL in Europeans, Which may explain the high incidence of follicular lymphoma in Europeans.

Disseminated Enterovirus Infection in a Patient Affected by Follicular Lymphoma Treated with Obinutuzumab: A Case Report and a Narrative Review of the Literature.

Background and Objectives: the principal purpose of this literature review is to cluster adults with hematological malignancies after treatment or on maintenance with obinutuzumab who experienced disseminated EV infection to understand clinical characteristics and outcome of this rare condition in these patients. We report the first clinical case of a male affected by follicular lymphoma treated with immune-chemotherapy including obinutuzumab who was affected by disseminated EV infection with cardiovascular involvement. Materials and Methods: this narrative review summarizes all the research about disseminated EV infection in immunosuppressed adult patients treated with obinutuzumab from January 2000 to January 2024 using the Scale for the Assessment of Narrative Review Articles (SANRA) flow-chart. We performed a descriptive statistic using the standard statistical measures for quantitative data. Results: we included six studies, five case reports, and one case report with literature analysis. We collected a total of seven patients, all female, with disseminated EV infection. The most common signs and clinical presentations of EV infection were fever and encephalitis symptoms (N = 6, 85.7%), followed by hepatitis/acute liver failure (N = 5, 71.4%). Conclusions: onco-hematological patients who receive immune-chemotherapy with a combination of treatments which depress adaptative immunity, which includes the antiCD20 obinutuzumab, could be at higher risk of disseminated EV infection, including CNS and cardiac involvement.

Follicular lymphoma B cells exhibit heterogeneous transcriptional states with associated somatic alterations and tumor microenvironments.

Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma of germinal center origin, which presents with significant biologic and clinical heterogeneity. Using RNA-seq on B cells sorted from 87 FL biopsies, combined with machine-learning approaches, we identify 3 transcriptional states that divide the biological ontology of FL B cells into inflamed, proliferative, and chromatin-modifying states, with relationship to prior GC B cell phenotypes. When integrated with whole-exome sequencing and immune profiling, we find that each state was associated with a combination of mutations in chromatin modifiers, copy-number alterations to TNFAIP3, and T follicular helper cells (Tfh) cell interactions, or primarily by a microenvironment rich in activated T cells. Altogether, these data define FL B cell transcriptional states across a large cohort of patients, contribute to our understanding of FL heterogeneity at the tumor cell level, and provide a foundation for guiding therapeutic intervention.

A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment.

Heterogeneity in the tumor microenvironment (TME) of follicular lymphomas (FLs) can affect clinical outcomes. Current immunotherapeutic strategies, including antibody- and cell-based therapies, variably overcome pro-tumorigenic mechanisms for sustained disease control. Modeling the intact FL TME, with its native, syngeneic tumor-infiltrating leukocytes, is a major challenge. Here, we describe an organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the native FL TME. We define the robustness of this method by successfully culturing cryopreserved FL specimens from diverse patients and demonstrate the stability of TME cellular composition, tumor somatic mutations, gene expression profiles, and B/T cell receptor dynamics over 3 weeks. PDLOs treated with CD3:CD19 and CD3:CD20 therapeutic bispecific antibodies showed B cell killing and T cell activation. This stable system offers a robust platform for advancing precision medicine efforts in FL through patient-specific modeling, high-throughput screening, TME signature identification, and treatment response evaluation.

Age and lymphocyte/monocyte ratio as prognostic factors for autologous transplantation in the treatment of patients with follicular lymphoma.

OBJECTIVE: Follicular lymphoma (FL) is an indolent, lymphoproliferative disease of B-cell origin that has a heterogeneous disease course with varying outcomes. Certain patients may undergo autologous stem cell transplantation. We investigated the outcome of autologous stem cell transplantation in patients with FL. METHODS: Patients who received autologous stem cell transplantation at the University of Debrecen's Department of Hematology between 2004 and 2021 were retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) after transplantation of patients with FL were examined. Prognostic factors that may influence the course of the disease were chosen. RESULTS: Data were collected from 49 patients. OS was influenced only by age, whereas PFS was affected by age and the lymphocyte/monocyte ratio. The combination of age and lymphocyte/monocyte ratio defined a patient population with a particularly unfavorable prognostic risk profile: patients over 47 years of age with a pre-transplant lymphocyte/monocyte ratio greater than or equal to 2.675. CONCLUSION: Age and lymphocyte/monocyte ratio were identified as useful prognostic factors for PFS in patients with FL following autologous stem cell transplantation.

Recurrent and persistent fever after SARS-CoV-2 infection in patients with follicular lymphoma: A case series.

Although persistent or recurrent COVID-19 infection is well described in some immunosuppressed patient cohort, to date, there have been no reports of this phenomenon in the context of repeatedly negative SARS-CoV-2 testing in the upper respiratory tract. We reported six patients with follicular lymphoma who developed recurrent symptomatic COVID-19 infection. They tested persistently negative for SARS-CoV-2 on pharyngeal swabs and ultimately confirmed by bronchoalveolar lavage fluid metagenomics next-generation sequencing. All six patients presented with lymphopenia and B-cell depletion, and five of them received the anti-cluster of differentiation 20 treatment in the last year. Persistent fever was the most common symptom and bilateral ground-glass opacities were the primary pattern on chest computed tomography. A relatively long course of unnecessary and ineffective antibacterial and/or antifungal treatments was administered until the definitive diagnosis. Persistent fever subsided rapidly with nirmatrelvir/ritonavir treatment. Our case highlighted that recurrent COVID-19 infection should be suspected in immunocompromised patients with persistent fever despite negative pharyngeal swabs, and urgent bronchoalveolar lavage fluid testing is necessary. Treatment with nirmatrelvir/ritonavir appeared to be very effective in these patients.

PET/CT in a 65-Year-Old Woman With Epstein-Barr Virus-Associated Smooth Muscle Tumor After Chemotherapy for Follicular Lymphoma.

ABSTRACT: The Epstein-Barr virus-associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder-associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus-associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.

Long-Term Follow-Up of the RESORT Study (E4402): A Randomized Phase III Comparison of Two Different Rituximab Dosing Strategies for Low-Tumor Burden Follicular Lymphoma.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In 2003, the Eastern Cooperative Oncology Group initiated a randomized phase III clinical trial (E4402) comparing two different rituximab dosing strategies for patients with previously untreated low-tumor burden follicular lymphoma. Rituximab-responsive patients (n = 299) were randomly assigned to either a retreatment rituximab (RR) strategy or a maintenance rituximab (MR) strategy. Each dosing strategy was continued until treatment failure. The primary end point of the study was time to treatment failure (TTF). In the original report, there was no difference in TTF between the two dosing strategies. Here, we report on the long-term outcomes for secondary end points of time to first cytotoxic therapy, duration of response, and overall survival (OS). At 7 years, 83% of MR patients had not required first chemotherapy compared with 63% of RR patients (hazard ratio, 2.37 [95% CI, 1.5 to 3.76]). At 7 years, 71% of MR remained in their first remission compared with 37% of RR patients. Despite the improved first remission length with MR, there was no difference in OS at 10 years (83% v 84%). With mature long-term data, we confirm that prolonged maintenance rituximab does not confer an OS advantage in low-tumor burden follicular lymphoma.