P1076: prevalence of somatic genetic mutations in hrs cells of hodgkin lymphoma patients from eastern mediterranean, assessed with, circulating tumor dna, differs from that found in european cohorts

Topic: 17. Hodgkin lymphoma - Clinical Background: The incidence of Hodgkin lymphoma (HL) among the Eastern Mediterranean population is very high. The highest rates are reported in Lebanese males (4.2x105) followed by Israeli males (3.7x105), with values being similar in Jews and Arabs. The corresponding rates for Israeli and Palestinian women are 3.6x105 and 3.3x105, respectively (1). In the last years, circulating tumor DNA (ctDNA) of Hodgkin and Reed/Sternberg (HRS) cells was identified as a surrogate biomarker for HL activity at diagnosis and follow-up (2,3). It is intriguing to find out if there is a difference in the frequency of specific somatic mutations in HRS cells between the Israeli population and published European cohorts. Aims: Assessment of frequency of specific somatic mutations associated with HRS cells in HL patients using paraffin embedded biopsy and ctDNA from paired plasma samples. Methods: In this study starting in 2021, patient samples were collected at diagnosis, prior to 2nd and 3rd cycles of chemotherapy and at the end of therapy. Treatment was initiated according to risk factors and modified based on interim PET. A set of 128 deep sequencing amplicons was generated to study 9 frequently mutated genes. DNA was sequenced using the Ion Torrent system. For each patient, paraffin embedded biopsy and ctDNA were evaluated. Results: Thirty-one patients were enrolled in the study, 13 of Arab and 18 of Jewish origin, including 13 males and 18 females at a median age of 32 (18-78) years, 15 pts were with advanced HL. Three patients had relapsed disease at presentation and were scheduled for salvage therapy followed by autologous stem cell transplantation (SCT). Initial therapy was ABVD/AVD in 16 pts, escBEACOPP in 9 pts, anti-PD1 in 4 pts and brentuximab vedotin plus ESHAP (BRESHAP) in 2 pts. To date, results on paraffin embedded biopsies of 20 pts along with matched ctDNA findings for 7 pts are available, while the evaluation of other pts is ongoing. Following exclusion of synonymous mutations, 114 nonsynonymous mutations were detected in the 9 genes. Forty-seven mutations were either nonsense and frameshift mutations. The variant allele frequency (VAF) of 0.5-5% was found in 96 mutations, VAF 6-10% in 4 mutations and VAF of 10-20% in 3 mutations. Overall, between 4-7 mutations were found in each patient. The frequency of specific somatic mutations in the 9 genes, identified in the current study was compared to that previously reported in two other studies (Table 1). ctDNA VAF levels were 10-fold higher than those found in paraffin embedded biopsy (results not shown). Summary/Conclusion: Preliminary results of this study suggest that the evaluation of ctDNA VAF in HL pts is feasible. The identified frequency of somatic gene mutations in the patient population included in the current study differs from that observed in European cohorts. This could imply the involvement of different mechanisms underlying HL pathogenesis in various geographical areas. Verification of these findings in larger cohorts may be beneficial. References 1.Levine H et al, Leuk Lymphoma 2017, 58:959–968 2.Camus V et al, Haematologica 2021, 106:154-162 3.Spina V et al, Blood 2018,131:2413-2425Keywords: Hodgkin’s disease, Hodgkin’s lymphoma, ctDNA