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.

Bone marrow reactive T-cell infiltrates have been frequently observed in patients affected by follicular lymphoma after rituximab treatment. In some studies, bone-marrow T-cell expansion has been associated with an effective anti-tumor response and favorable prognosis. In this manuscript, we report on a particularly brisk CD4+ T-cell reaction occurring after rituximab treatment for follicular lymphoma and involving the peripheral blood in addition to the bone marrow. Peripheral blood T-cell reaction was mainly composed of effector-memory CD4+ T cells and may reflect the expansion of an effective anti-tumor immunity.

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype, accounting for 15-20% of all lymphoma diagnoses. Although typically slow-growing and responsive to frontline therapies, advanced-stage FL remains incurable with current treatments and typically follows a chronic relapsing/remitting course with increasingly shorter responses to subsequent lines of therapy. Outcomes are highly variable; some patients experience prolonged first remissions that may approximate a \'functional cure\'. By contrast, a significant minority of patients experience disease progression shortly after frontline treatment resulting in high rates of lymphoma-related mortality. Reflecting on the heterogeneous natural history of FL, clinical practice varies widely, particularly in controversial areas, including appropriate disease staging, selection of management strategies and duration of clinical follow-up. This position statement presents an evidence-based synthesis of the literature for application in Australasian practice.

BACKGROUND: \"Watch-and-wait\" approach is an important management option in asymptomatic follicular lymphoma (FL) patients with low tumor burden. Since most FL lesions are FDG-avid, we wonder if 18F-FDG PET/CT at baseline can help to better choose the patients who can benefit from early chemotherapy. This study aimed to investigate the prognostic value of baseline 18F-FDG PET/CT in newly diagnosed FL patients treated with either watch-and-wait approach or chemotherapy.
RESULTS: Patients received chemotherapy as initial treatment had higher Ann Arbor stage, higher incidence of extranodal involvement and bulky disease, more involved lymph nodes larger than 3 cm, and higher SUVmax, MTV, and TLG than those managed with watch-and-wait approach (p < 0.05). The median PFS and TTNT in patients received chemotherapy and under watch-and-wait did not show significant difference, however patients with MTV<111.66 mL or TLG<141.50 SUVbw*mL had significantly longer PFS and TTNT than those patients with MTV≥111.66 mL or TLG≥141.50 SUVbw*mL (p < 0.05). Further analysis revealed that for patients with TLG≥141.50 SUVbw*mL or MTV≥111.66 mL, those who received chemotherapy as initial treatment had a significantly longer PFS and TTNT than those managed with initial watch-and-wait approach (p < 0.05). However, for patients with MTV<111.66 mL or TLG<141.50 SUVbw*mL in baseline PET/CT, there was no significant difference in PFS or TTNT between patients who received chemotherapy and those under watch-and-wait.
CONCLUSIONS: Baseline 18F-FDG PET/CT may provide prognostic value and help to improve the decision-making of initial treatment plans for newly diagnosed FL patients.

Background: Deep learning models for patch classification in whole-slide images (WSIs) have shown promise in assisting follicular lymphoma grading. However, these models often require pathologists to identify centroblasts and manually provide refined labels for model optimization. Objective: To address this limitation, we propose PseudoCell, an object detection framework for automated centroblast detection in WSI, eliminating the need for extensive pathologist\'s refined labels. Methods: PseudoCell leverages a combination of pathologist-provided centroblast labels and pseudo-negative labels generated from undersampled false-positive predictions based on cell morphology features. This approach reduces the reliance on time-consuming manual annotations. Results: Our framework significantly reduces the workload for pathologists by accurately identifying and narrowing down areas of interest containing centroblasts. Depending on the confidence threshold, PseudoCell can eliminate 58.18-99.35% of irrelevant tissue areas on WSI, streamlining the diagnostic process. Conclusion: This study presents PseudoCell as a practical and efficient prescreening method for centroblast detection, eliminating the need for refined labels from pathologists. The discussion section provides detailed guidance for implementing PseudoCell in clinical practice.

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056.

Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 106 or 1 × 107 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 105 to 5 × 107.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.

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