CD19-targeted therapies, including monoclonal antibodies, antibody–drug conjugates, and chimeric antigen receptor (CAR) T-cell products, have significantly improved outcomes in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Despite their clinical efficacy, resistance and antigen modulation pose substantial challenges, especially in patients requiring sequential therapy. This review provides a comprehensive overview of CD19 biology and its relevance as a therapeutic target. We examine mechanisms of resistance such as antigen loss, epitope masking, and T-cell exhaustion, as well as the implications of tumor microenvironmental immunosuppression. Future efforts should prioritize the integration of real-time diagnostics, such as flow cytometry, immunohistochemistry, and transcriptomic profiling, and AI-assisted predictive models to optimize therapeutic sequencing and expand access to personalized immunotherapy.

Hodgkin lymphoma (HL) treatment has dramatically improved, with high survival rates in early stages. However, long-term survivors face an increased risk of secondary cancers, particularly breast cancer (BC), which emerge as a leading cause of mortality decades after therapy. Background/Objectives: This study explores the risk of BC and the toxic effects of radiation therapy (RT) in long-term HL survivors compared to age-matched high-risk women, including BRCA1 and BRCA2 mutation carriers. A prospective study was conducted on 62 women who had undergone chemotherapy and involved-field RT for HL, with MRI used to assess breast tissue changes. This study’s primary endpoint was to analyze BC incidence in HL survivors, while secondary objectives focused on the analysis of background parenchymal enhancement (BPE) in irradiated areas. Results: The findings revealed a 5% incidence of BC in HL survivors, with 50% showing moderate or marked BPE, similar to that observed in high-risk BC controls. No significant differences in BPE distribution were found between the two groups. Conclusions: The study highlights the long-term risk of BC in HL survivors and suggests that advanced RT techniques and targeted therapies may help reduce the incidence of secondary tumors. Future research should focus on understanding the genetic and biological mechanisms behind treatment-induced cancers

Background: Classical Hodgkin lymphoma (cHL) is a treatable malignancy; however, relapsed or refractory (R/R) cases pose significant challenges. PD-1 inhibitors have shown efficacy, but the role of hematopoietic stem cell transplantation (HSCT) following PD-1 blockade remains uncertain. This study aims to evaluate the impact of HSCT after PD-1 blockade on progression-free survival (PFS) and overall survival (OS) in patients with R/R cHL. Methods: We conducted a multicenter, retrospective study involving 42 patients with R/R cHL who received PD-1 inhibitors between 2016 and 2021. Patients were categorized into two groups: those who underwent HSCT after PD-1 therapy (n = 19) and those who continued PD-1 inhibitors without HSCT (n = 23). Results: Among the 42 patients, 27 achieved complete remission (CR) and 15 achieved partial remission (PR) following PD-1 blockade. In the HSCT group, 92% of patients remained progression-free at 3 years, compared to 65% in the non-HSCT group (p = 0.021). OS rates were similar between groups (100% vs. 96%, p = ns). Notably, 80% of PR patients in the HSCT group converted to CR. Relapse rates were significantly lower in the HSCT group (5%) compared to the non-HSCT group (43%, p = 0.005). Conclusions: HSCT following PD-1 blockade enhances PFS in patients with R/R cHL, particularly among those with PR, without offering a significant OS benefit. Further research is warranted to optimize treatment strategies for this patient population strategies.

Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell malignancy that may exhibit resistance to standard chemoimmunotherapy. Novel immunotherapeutic strategies, including checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapy, are being explored in cases that are refractory to treatment. We report the case of a 29-year-old patient with refractory PMLBCL who was treated with pembrolizumab as a bridging therapy followed by axicabtagene ciloleucel (CAR-T) after failing R-CHOP and R-DHAP regimens. Initial disease progression following pembrolizumab was consistent with an immune-related flare phenomenon. Subsequent CAR-T infusion led to a complete metabolic response. Immunologic monitoring revealed expansion of CD3+ and CD56+ lymphocyte subsets, suggesting immune activation. Notably, the patient maintained normal endocrine function and conceived spontaneously three years post-treatment, delivering a healthy infant at term. This case highlights the potential synergy between checkpoint inhibition and CAR-T cell therapy in refractory PMLBCL, providing rare evidence of preserved fertility following intensive immunotherapy. Early recognition of immune flare and multidisciplinary management are critical in optimizing outcomes for young patients receiving novel immunotherapeutic approaches.