OBJECTIVE: Previous results about prognostic value of CD4+ T cells in follicular lymphoma (FL) remain controversial.
METHODS: Immunohistochemistry was used to examine expression of positive CD4 cells in 103 patients with FL 1-3A. Early failure was described as failing to achieve event-free survival (EFS) at 12 or 24 months.
RESULTS: There were 49 (47.6%) male and 54 (52.4%) females, with a median age of 54 years. Compared to patients with <20% of positive CD4 cells, patients with ≥20% of positive CD4 cells exhibited a significant lower risk of early failure (2-year EFS rate: 56.7% vs 73.5%, p = 0.047). When patients were stratified based on positive CD4 cell combined with FLIPI, the median EFS (p = 0.002) and median OS (p = 0.007) were significantly different.
CONCLUSIONS: This study demonstrated that higher expression of positive CD4 cells predicts lower risk of early failure in follicular lymphoma, and combination analysis of CD4 and FLIPI could better predict disease relapse and survival outcome.

[This corrects the article DOI: 10.3389/fimmu.2024.1391404.].

Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), there remains a lack of biomarker-directed therapeutic approaches in routine clinical practice, with the notable exception of the EZH2 inhibitor tazemetostat in EZH2-mutant FL. Here we examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of biopsies from 21 relapsed/refractory FL patients treated with mTORi everolimus or temsirolimus within clinical trials. We observed an enrichment of mutations within the catalytic histone acetyltransferase (HAT) domain of CREBBP in mTORi-responders, and describe distinct transcriptional characteristics and co-occurring mutations of FL harbouring these mutations; reinforcing the growing appreciation of CREBBPHAT mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.

Apart from bone marrow involvement, extranodal involvement of follicular lymphoma (FL) is rare. Gynecologic FL is seldom reported, among which the vagina is the rarest involved site. No vaginal involvement in advanced-staged FL was reported before. Here, we report a case of FL with systemic involvement including the vagina.

Follicular lymphoma (FL) is an indolent, germinal center B cell-derived lymphoid neoplasm, for which recent advances in treatment have substantially improved patient survival. However, FL remains an incurable and heterogeneous disease, with groups of patients experiencing early disease progression, histologic transformation, or a high risk of treatment-related toxicity. Additionally, FL is a continually relapsing disease, and response rates and disease-control intervals decrease with each subsequent line of therapy. In this review, we explore the current treatment landscape for relapsed or refractory FL and promising therapies in development, highlighting the efficacy and potential risks of each treatment. We provide a real-world perspective on the unmet needs of patients with FL. Novel therapeutic approaches in development offer a wide array of options for clinicians when treating relapsed or refractory FL. A nuanced approach is required to address the needs of individual patients, taking into consideration both the risks and benefits of each treatment option, as well as patient preferences.

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UNASSIGNED: Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma.
UNASSIGNED: In this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at the MD Anderson Cancer Center. We excluded patients with evidence of ongoing transformation to aggressive lymphoma. During phase 1, 1000 mg intravenous obinutuzumab was administered with three predefined levels of oral lenalidomide in a 3 + 3 dose escalation design to establish lenalidomide 20 mg as the recommended phase 2 dose. During phase 2, patients received induction therapy with six 28-day cycles of lenalidomide 20 mg with intravenous obinutuzumab 1000 mg. In accordance with our prior experience with lenalidomide plus rituximab, patients who were responding to the combination could receive up to 6 additional cycles (up to 12 cycles in total) of combination therapy. Dosing of obinutuzumab was continued in all responding patients after cycle 6 every 2 months for a total of 30 months from the start of therapy. The decision of number of cycles of combination therapy beyond 6 was at discretion of the investigator and was included to allow individualisation of therapy to maximise response while minimising exposure. The co-primary objectives were to evaluate the safety and overall response, defined as the proportion of patients who achieved a complete or partial response in relapsed and refractory indolent non-Hodgkin lymphoma at the end of induction therapy, according to Cheson and colleagues (2007 criteria). The secondary endpoints were complete response after induction therapy and time to event endpoints including time to progression, progression free survival, and overall survival. Analyses were intent to treat in the efficacy cohort and per-treated in the safety population in all patients who received at least one dose of either investigational agent. This trial is registered with ClinicalTrials.gov, NCT01995669.
UNASSIGNED: Between June 03, 2014, and 07 March 2019, we completed planned enrolment, and 66 patients started therapy including 9 patients in phase 1 and 57 patients in phase 2. All patients were evaluated for safety and the 60 patients treated at the recommended phase 2 dose of lenalidomide 20 mg were evaluable for activity. Grade 3-4 haematological toxicities included neutropenia 21% (14/66) and thrombocytopenia 11% (7/66) with no cases of febrile neutropenia. Grade 3-4 non-haematological toxicities included lung infection 8% (5/66), fatigue 8% (5/66) and rash 6% (4/66). By Cheson 2007 criteria, 90% (54/60, 95% CI: 79-96) achieved an overall response at the end of induction meeting the prespecified activity endpoint. Complete responses were seen in 33% (20/60, 95% CI: 22-47) at the end of induction. Median progression free survival, time to progression and overall survival have not been reached after median follow-up of 41.7 months. Estimated 4-year progression free survival rates were 55% (95% CI: 42-73), time to progression of 56% (95% CI: 43-74) and overall survival of 84% (95% CI: 74-95).
UNASSIGNED: Our findings suggest that oral lenalidomide with obinutuzumab is safe and highly active in patients with relapsed and refractory indolent B cell non-Hodgkin lymphoma and is associated with prolonged remission duration. The study is limited by the lack of a control arm leading to cross-trial comparisons to evaluate activity. Future randomised trials comparing this regime to rituximab and lenalidomide are warranted.
UNASSIGNED: Genentech and an MD Anderson Core grant.

BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma.
METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma (FL) after ≥2 lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in Cycle 1 to help mitigate the risk of cytokine release syndrome (CRS), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review.
RESULTS: Among 128 patients evaluated, 95% completed Cycle 1, and 85% completed ≥4 cycles. At 20.1 months\' efficacy follow-up, ORR was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events (AEs) occurred in 16% of patients. The most common treatment-emergent AEs were CRS (56%; grade ≥3 1.7% [1/60] with 0.7/4/20 mg step-up), neutropenia (39%), and pyrexia (38%).
CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R FL.

BACKGROUND: PTC has high lymph node metastasis, affecting central and lateral lymph nodes. On the other hand, follicular lymphoma is the second most frequent non-Hodgkin lymphoma in the West and affects cervical lymph nodes.
METHODS: A 66-year-old Saudi man with type 2 diabetes and hypertension presented with neck lumps on both sides of his neck. The swelling was progressive, with no apparent cause, no history of hypothyroidism or hyperthyroidism, and no constitutional symptoms. Physical examination revealed multiple lymph node enlargements and a hard, firm mass on his thyroid gland.
UNASSIGNED: Multiple malignant neoplasms are rare, but secondary primary cancers have been documented in patients with PTC. The occurrence of both cancers is commonly detected during follow-up and aided by modern imaging techniques. The main treatment for PTC is surgery, usually with a good prognosis.
CONCLUSIONS: A 66-year-old male was diagnosed with follicular lymphoma during a papillary thyroid carcinoma workup, emphasizing the importance of careful lymph node dissection and microscopic examination for rare cases.

This case report presents the clinical findings, diagnostic evaluation, and treatment options for a 71-year-old female patient with a medical history of hypertension, dyslipidemia, and recurrent urinary tract infections. The patient presented with chronic abdominal pain as the sole symptom. Despite normal laboratory investigations, esophagogastroduodenoscopy and ileocolonoscopy were performed. Biopsies were obtained from the duodenum and histopathological analysis confirmed a diagnosis of duodenal-type follicular lymphoma. This rare condition typically presents with minimal clinical symptoms and has a favorable prognosis. Treatment options for duodenal-type follicular lymphoma include a watch-and-wait strategy, rituximab monotherapy, and radiotherapy.