Abstract 3831: Clinicopathologic determinants of survival in double/triple hit lymphoma: Analysis of a pooled database
Authors: Haddad Philip A. , Gupta Supriya , Gupta Ankita , Graham Christopher 
Published: March 2024

Abstract
Background B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements are classified as double/triple- hit lymphoma (DTHL). They usually, but not always, tend to be high-grade aggressive B-cell lymphoma with worse prognosis. Despite this classification, DTHL remains a heterogeneous group with varied molecular profiles, biological behavior, and prognosis. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies influencing survival in this rare disease.
Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 161 cases that fit the diagnostic criteria for DTHL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS).
Results A compiled a dataset of 161 patients with confirmed DTHL. The median age was 62 with F:M of 1.08. The median duration of symptoms before diagnosis was 2 months. DTHL involved the lymph nodes (41%), bone marrow (31%), bone (14%), CNS (5%), skin (4%), liver (3%), and spleen (2%). Constitutional symptoms were reported in 20%. The cohort consisted of primary (50%), secondary/transformed (16%), and follicular DTHL. The median OS and DFS of the cohort were 69 and 27 months, respectively. Bone marrow and extra-lymphatic organ involvement were associated with worse DFS and non-significant numerically worse OS. LDH&gt;500 (p=0.006), PAX5-negative (p=0.01), CD79a-negative (p=0.02), and Ki67&gt;80% (p&lt;0.0001) were associated with worse OS. Similarly, CD5+, CD10+, and MUM1+ had worse OS, but did not reach statistical significance. Follicular DTHL was associated with the best median OS and DFS followed by primary then secondary/transformed in decreasing order. Advanced stage and high IPI were also associated with worse non-significant numerical OS. Age and sex did not impact OS. Compared to no treatment, chemotherapy and stem cell transplant had incrementally superior median OS (3 vs. 55 vs. NR months, p=0.008). Frontline intensive chemotherapy yielded similar DFS and OS to CHOP-like regimens. Patients who attained CR as their best response also had a superior median OS (p&lt;0.0001).
Conclusion This study presents clinicopathologic data from a cohort of patients with primary, secondary, and follicular DTHL. It identifies the type of DTHL, IHC profile, LDH levels, type of therapy, and quality of response to treatment as critical determinants of OS.
Citation Format: Philip A. Haddad, Supriya Gupta, Ankita Gupta, Christopher Graham. Clinicopathologic determinants of survival in double/triple hit lymphoma: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3831.