Somatic mutations of genes involved in NF-κB, PI3K/AKT, NOTCH, and JAK/STAT signaling pathways play an important role in the pathogenesis of Hodgkin lymphoma (HL). HL tumor cells form only about 5% of the tumor mass; however, it was shown that HL tumor-derived DNA could be detected in the bloodstream. This circulating tumor DNA (ctDNA) reflects the genetic profile of HL tumor cells and can be used for qualitative and quantitative analysis of tumor-specific somatic DNA mutations within the concept of liquid biopsy. Overall, the most frequently mutated gene in HL is STAT6; however, the exact spectrum of mutations differs between individual HL histological subtypes. Importantly, reduction of ctDNA plasma levels after initial treatment is highly correlated with prognosis. Therefore, ctDNA shows great promise as a novel tool for non-invasive tumor genome analysis for biomarker driven therapy as well as for superior minimal residual disease monitoring and treatment resistance detection. Here, we summarize the recent advancements of ctDNA analysis in HL with focus on ctDNA detection methodologies, genetic profiling of HL and its clonal evolution, and the emerging prognostic value of ctDNA.

Patients with chronic lymphocytic leukemia (CLL) have a high risk of poor outcomes related to coronavirus disease 2019 (COVID-19). This multicenter cohort study evaluated the impact of COVID-19 infection on the population of CLL patients in the Czech Republic. Between March 2020 and May 2021, 341 patients (237 males) with CLL and COVID-19 disease were identified. The median age was 69 years (range 38–91). Out of the 214 (63%) patients with the history of therapy for CLL, 97 (45%) were receiving CLL-directed treatment at diagnosis of COVID-19: 29% Bruton tyrosine kinase inhibitor (BTKi), 16% chemoimmunotherapy (CIT), 11% Bcl-2 inhibitor, and 4% phosphoinositide 3-kinase inhibitor. Regarding the severity of COVID-19, 60% pts required admission to the hospital, 21% pts were admitted to the intensive care unit (ICU), and 12% received invasive mechanical ventilation. The overall case fatality rate was 28%. Major comorbidities, age over 72, male gender, CLL treatment in history, CLL-directed treatment at COVID-19 diagnosis were associated with increased risk of death. Of note, concurrent therapy with BTKi compared to CIT was not associated with better outcome of COVID-19.

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Introduction. EORTC H10 trial confirmed better selection of patients who needed reduced or more intensive treatment using PET response after 2 cycles of ABVD in early stages of classical Hodgkin lymphoma (cHL). GHSG HD17 showed that radiotherapy can be safely omitted in PET4-negative early unfavorable HL treated with 2 cycles of BEACOPP escalated plus 2 cycles of ABVD (2+2 chemotherapy). We compared PET2-adapted approach including 30Gy involved-node radiotherapy (INRT) with 2+2 chemotherapy followed by 30 Gy INRT (or involved-field radiotherapy, IFRT) regardless of interim PET in patients with early unfavorable cHL assessed according to the GHSG risk factors. Methods. Overall 243 patients with early unfavorable cHL (aged 18-60 years) prospectively observed in the Czech Hodgkin lymphoma study group registry between 2003-2020 were analyzed. Patients in clinical stage IIB with massive mediastinal tumor and/or with extranodal disease were not included into this analysis as they were treated with BEACOPP escalated only. Chemotherapy 2+2+30 Gy INRT/IFRT received 213 patients. Overall 30 patients were treated with PET2-adapted approach: 29 PET2-negative patients received 4 cycles of ABVD and 30 Gy INRT and one PET2-positive patient was treated with 2 cycles of ABVD plus 2 cycles of BEACOPP escalated and 30 Gy INRT. Results. Median age at the time of cHL diagnosis was 32 (range 18-59) years. Median follow-up was longer in the 2+2+INRT/IFRT group (91.3, range 6.2-211.2) months when compared to the PET2-adapted approach (19.4, range 6.4-90.4) months. The estimated 2-year progression-free survival (PFS) did not differ in both groups (100% [95% CI 100-100] both), however, the estimated 5-year PFS was significantly better in the 2+2+INRT/IFRT group (99.5% [95% CI 98.5-100]) in comparison to PET2-adapted treatment (75.0% [95% CI 32.5-100]), p<0.001. The estimated 5-year overall survival was comparable in both groups (2+2+INRT/IFRT: 99.5% [95% CI 98.5-100]; PET2-guided treatment: 100% [95% CI 100-100]). Hematological toxicity was reported in most of the patients in both groups. Grade 3 non-hematological toxicity occured in 3 patients in the 2+2+INRT/IFRT approach (2 infections, 1 deep vein thrombosis). Conclusion. This retrospective analysis indicates that 2+2+INRT/IFRT is more effective in the long-term disease control, but there is no difference in overall survival in both groups. The current approach includes 2+2 chemotherapy and INRT is added in PET4-positive patients. This work was supported by the Research project Q 28 Progres awarded by the Third Faculty of Medicine of Charles University in Prague in the Czech Republic. Disclosures Belada: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding.