Background: Follicular lymphoma (FL) is the second most common B-cell lymphoma in Western countries, typically presenting as an indolent disease with prolonged overall survival. Despite favorable initial responses to therapy, most patients experience relapse, and early progression is associated with poor outcomes. Methods: This guideline provides evidence-based recommendations from the Spanish GELTAMO group on the diagnosis, staging, treatment, and follow-up of FL. A systematic literature review was conducted, and recommendations were graded according to the GRADE system. Results: Histopathological diagnosis should be based on excisional biopsy. PET-CT is recommended for staging and response evaluation. For localized disease, involved-site radiotherapy (ISRT) remains the treatment of choice. In asymptomatic patients with advanced-stage disease and low tumor burden, a watch-and-wait approach is appropriate, although rituximab monotherapy is also acceptable. For advanced-stage disease with high tumor burden, immunochemotherapy with anti-CD20 antibodies (rituximab or obinutuzumab) combined with CHOP, CVP, or bendamustine is recommended, followed by maintenance therapy. Management of relapsed disease is tailored based on tumor burden, treatment history, and timing of relapse. Although novel immunotherapies (CAR-T therapy and bispecific antibodies) are emerging as promising options, autologous stem cell therapies may still be a valid option in young patients with early relapse who are sensitive to immunochemotherapy. Conclusions: FL is a heterogeneous disease requiring individualized management strategies. Recent advances in immunotherapy and molecular diagnostics are reshaping the therapeutic landscape. These updated GELTAMO recommendations aim to provide practical guidance for optimal FL management in clinical practice.

Purpose: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. Methods: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA LiqBio and paired gDNA tissue biopsies at diagnosis and compared the mutational statuses. Also, through NGS of LiqBio, we identified MRD biomarkers and compared this novel LiqBio–MRD method with PET/CT in detecting MRD at follow-up. Results: We identified mutations in 71% of LiqBio and 95% of tissue biopsies, and found a correlation between variant allele frequency of somatic mutations. Additionally, we identified mutations in 73% of LiqBio from patients with no available tissue samples or no mutations in them. Regarding the utility of LiqBio–MRD as a dynamic monitoring tool, when compared with the PET/CT method, a lower sensitivity was observed for LiqBio–MRD at 92.3% (vs. 100% for PET/CT), but a higher specificity of 91.3% (vs. 86.9% for PET/CT). Conclusion: Genetic profiling of tumor cfDNA in plasma LiqBio is a complementary tool for BCL diagnosis and MRD surveillance.

Non-Hodgkin lymphoma is a heterogeneous group of cancers that triggers bone marrow infiltration in 20–40% of cases. Bone marrow biopsy in combination with a visual assessment of [¹⁸F]FDG PET/CT images is used to assess the marrow status. Despite the potential of both techniques, they still have limitations due to the subjectivity of visual assessment. The present study aims to develop models based on bone marrow uptake in [¹⁸F]FDG PET/CT images at the time of diagnosis to differentiate bone marrow status. For this purpose, a model trained for skeleton segmentation and based on the U-Net architecture is retrained for bone marrow segmentation from CT images. The mask obtained from this segmentation together with the [¹⁸F]FDG PET image is used to extract radiomics features with which 11 machine learning models for marrow status differentiation are trained. The segmentation model yields very satisfactory results with Jaccard and Dice index values of 0.933 and 0.964, respectively. As for the classification models, a maximum F1_score_weighted and F1_score_macro of 0.962 and 0.747, respectively, are achieved. This highlights the potential of these features for bone marrow assessment, laying the foundation for a new clinical decision support system.

Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line. A total of 38.2% had received a previous autologous stem cell transplantation (ASCT), and 61.7% had received both an immunomodulatory drug (IMID) and a proteasome inhibitor (PI). The median overall survival (OS) was 21 months for the global cohort but it decreased to 14 months for triple-class refractory patients and 5 months for penta-refractory patients. Most of the patients (83.9%) received treatment after daratumumab progression, in many cases with second generation IMID or PI, but seven patients were treated with anti-BCMA therapy and three patients received CART therapy within a clinical trial. In conclusion, patients R/R to daratumumab represent an unmet clinical need with poor prognosis and in need of incorporation of new treatments.

The authors would like to make the following corrections to this published paper