Bispecific antibodies represent a pivotal advancement in treating relapsed/refractory B-cell lymphomas, addressing unmet needs for patients with limited conventional options. This review examines CD20 × CD3 bispecific antibodies (BsAbs) like mosunetuzumab, epcoritamab, odronextamab, and glofitamab, which link malignant B-cells and T-cells, thus inducing targeted tumor lysis. These IgG-like molecules activate T-cells, triggering proliferation and cytotoxic molecule release, bypassing MHC presentation. These agents have received regulatory approval for the treatment of various B-cell lymphomas and exhibit substantial efficacy, with high overall and complete response rates in diffuse large B-cell lymphoma and follicular lymphoma. However, their use is associated with immune-related toxicities. Cytokine Release Syndrome, which is a systemic inflammatory response due to a cytokine surge, and Immune Effector Cell-Associated Neurotoxicity Syndrome, linked to endothelial activation and blood–brain barrier disruption, are critical concerns. This review details their mechanisms, grading, and management, including the use of tocilizumab and corticosteroids. Furthermore, BsAb therapy carries an elevated susceptibility to viral, bacterial, and opportunistic infections, often exacerbated by hypogammaglobulinemia. Expert recommendations for antimicrobial prophylaxis, including herpes and varicella zoster virus, pneumocystis, and immunoglobulin supplements are crucial for mitigating these risks. While BsAbs offer an “off-the-shelf” advantage, balancing their efficacy with comprehensive toxicity management is crucial for maximizing patient outcomes.

Background and Objectives: The overall- and progression-free survival rates of Hodgkin’s lymphoma patients have improved. Our goal was to examine the changes in our treatment results and their causes depending on the daily diagnostic and therapeutic practice. Materials and Methods: We analysed data of 776 classical Hodgkin lymphoma patients treated between 1980 and 2019. Patient data were investigated in ten-year periods (first period: 1980–1989, second period: 1990–1999, third period: 2000–2009, and fourth period: 2010–2019). Results: Radiotherapy alone as a first-line treatment was used progressively less often, and in the 4th period it was no longer used before or without chemotherapy. The use of combined chemo- and radiotherapy decreased in the last period, and the number of those patients who received only chemotherapy increased significantly. The 10-year overall survival improved significantly from 1990 to 1999 compared to 2010 to 2019 (74.9% vs. 86.9%). About 30% of patients relapsed after or were refractory to first-line therapy in each period. The incidence of relapse in the last period did not increase after two years, but there was no significant difference between the periods. Conclusions: Overall survival rates of HL patients have improved significantly in recent decades, which is due to improved diagnostic methods and modern therapies. Progression-free survival is unchanged; one-third of patients relapse or are refractory to first-line treatment within the first two years. Early recognition of R/R patients, the early application of newer and already available innovative therapies, and the finding of additional new and effective therapies are of particular importance.

Background/Objectives: Hodgkin lymphoma (HL) primarily affects young adults, but about 20% of cases occur in patients over the age of 60 years. Older individuals often have comorbidities and poorer functional status, which can affect treatment choices. Methods: We retrospectively analyzed data from HL patients over 60 years old who were treated at our institution between January 2010 and December 2023. We examined various factors, such as blood parameters (e.g., platelet count, lactate dehydrogenase (LDH), C-reactive protein (CRP)), PET/CT results and comorbidities (e.g., hypertension, diabetes, cardiovascular diseases), to assess their impact on overall survival (OS) and progression-free survival (PFS). Diagnostic efficiency was determined via receiver operating characteristic analysis, while the survival outcomes were evaluated using the Cox proportional hazards model. Results: A total of 35 patients with a median age of 68 were treated. The most common subtype was nodular sclerosis, and 72% of patients were in advanced stages at diagnosis. Treatment varied by age, with younger patients receiving ABVD and older patients (80–89) receiving brentuximab vedotin with dacarbazine. The survival of older patients, when analyzed by age groups, did not show a significant difference in the OS (p = 0.16) and PFS (p = 0.11). Comorbidities significantly worsened survival, with patients who scored > 7 on the Charlson Comorbidity Index (CCI) showing a 5-year PFS of 41.3%, compared to 91.3% for those who scored ≤ 7. Among the tested laboratory parameters, a platelet count over 310.5 G/L and an absolute lymphocyte count below 0.47 G/L were found to be independent risk factors for OS. Patients with neither or only one of these risk factors demonstrated a 5-year OS of 81.7%, whereas those presenting with both risk factors experienced a reduced 5-year OS of 70%. For PFS, a white blood cell count > 8.48 G/L, a platelet count > 310.5 G/L, and advanced age (>73.5 years) were identified as significant adverse prognostic factors. Patients with none of these risk factors had a 5-year PFS of 100%, whereas those with ≥ 1 risk factor had a 5-year PFS of 35.6%. Conclusions: Comorbidities play a greater role in prognosis than chronological age, emphasizing the need for personalized treatment approaches.

Background and Objectives: Autologous stem cell transplantation (ASCT) remains the standard of care for relapsed or refractory Hodgkin lymphoma (R/R HL), and an increasing proportion of patients receive programmed cell death protein 1 (PD-1) inhibitors prior to transplantation. Engraftment syndrome (ES) is a noninfectious inflammatory complication classically associated with neutrophil recovery; however, early peri-transplant inflammatory manifestations remain poorly characterized and may mimic infectious complications. We aimed to evaluate peri-transplant inflammatory events after ASCT, with particular emphasis on ES-compatible manifestations occurring before neutrophil engraftment and their association with prior PD-1 inhibitor exposure. Materials and Methods: In this single-center retrospective cohort study, 64 consecutive adult patients with HL undergoing ASCT between 2018 and 2025 were analyzed. ES was defined according to Spitzer and Maiolino criteria. Inflammatory manifestations fulfilling these criteria but occurring prior to neutrophil recovery were classified as pre-engraftment syndrome (pre-ES). Clinically significant events were defined by the requirement for systemic corticosteroid therapy. Clinical and laboratory parameters were compared using non-parametric statistical analyses. Results: No cases fulfilled the Spitzer criteria for classical ES, while three patients (4.7%) met the Maiolino criteria, none requiring corticosteroid therapy. Using the broader Maiolino definition, pre-ES was observed in 34 patients (53.1%) when the conventional engraftment time window was disregarded; however, only three patients required systemic corticosteroid therapy. Importantly, all three cases also fulfilled the Spitzer criteria outside the conventional time window, whereas the remaining Maiolino-defined pre-ES cases were self-limiting. All steroid-requiring pre-ES cases occurred exclusively in PD-1-exposed patients, and prior PD-1 therapy was significantly associated with severe pre-ES (p = 0.0007), although this finding is based on a very small number of events. These patients also demonstrated significantly higher early C-reactive protein (CRP) levels. Conclusions: While classical ES after ASCT was uncommon, clinically significant pre-ES occurred exclusively in PD-1-exposed patients. These early inflammatory events may represent a distinct phenotype and require prompt recognition and timely corticosteroid therapy after exclusion of infection. Prospective studies are warranted to validate these findings and refine risk stratification and monitoring strategies.

Background/Objectives: Hodgkin lymphoma (HL) represents a rare but clinically significant complication in patients with Common Variable Immunodeficiency (CVID). Immune dysregulation, impaired viral control, and Epstein–Barr virus (EBV) infection may contribute to pathogenesis and adversely affect treatment tolerance. This case-based review aims to highlight the impact of early CVID recognition and multidisciplinary management on outcomes in CVID-associated HL. Methods: A retrospective screening of 224 patients with HL treated at our institution between 2010 and 2023 identified two individuals with CVID and EBV-positive HL. These cases are presented in detail and contextualized within a structured review of the published literature. Results: The first patient, diagnosed with CVID prior to HL onset, received immunoglobulin replacement and a modified chemotherapy regimen substituting bleomycin with brentuximab vedotin, resulting in sustained complete remission. The second patient, in whom CVID was recognized only after HL relapse, experienced recurrent infections, intolerance to therapy, and fatal disease progression despite treatment with brentuximab vedotin, checkpoint inhibition, and rituximab. The literature review revealed only eight comparable cases, underscoring the rarity and complexity of this association. Conclusions: Early identification of CVID facilitates infection control and enhances tolerance to HL therapy, thereby improving clinical outcomes. Multidisciplinary, individualized management and incorporation of targeted agents are pivotal in optimizing care for this vulnerable population.