Abstract 3835: Clinicopathologic determinants of survival in malignant histiocytic neoplasms: Analysis of a pooled database

Abstract

Abstract Background: Malignant histiocytosis, also known as the M-group per the Histiocyte Society classification, represents a rare, aggressive malignant group of histiocytic neoplasms. It includes histiocytic neoplasms that occur de novo (pMHN) and those that develop in association with other malignant diseases (aMHN). However, little is known about factors that impact MHN clinical outcomes. We conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in these rare diseases. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 281 cases of MHN. 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). Results: A total of 281 patients with confirmed MHN were identified, with 77% pMHN and 23% aMHN. The median age was 45, with bimodal peaks between 0-13 and 52-65. There was a male preponderance with M:F of 1.6. Primary sites of involvement were liver (15%), CNS and spleen (13% each), thoracic, GI, and soft tissues (12% each), bones (11%), skin (10%), H&N (8%), and breast, heart, gonads, pancreas, and kidney (1% each). Lymphadenopathy and bone marrow (BM) were involved in 28% and 18%, respectively. Constitutional symptoms occurred in 12% and hemophagocytic syndrome (HPS) in 6%. The median OS of the whole group was 12 months. BM involvement had a worse median OS (5 vs. 60 months, p=0.0002). Stage 1 disease had better median OS than higher stages (p=0.0008). Furthermore, unifocal had better median OS than multifocal/multicentric disease (60 vs. 7 months, p=0.0001). The presence of inflammatory background positively impacted OS (p=0.01). The occurrence of HPS adversely affected OS (p<0.0001). Compared to no treatment, localized therapies such as surgery (S) and/or radiation therapy (RT) and systemic combination chemotherapy (CT) were statistically superior, with a median OS of 3, 24, and 16 months, respectively (p=0.009). Among systemic therapies, SCT and BRAF/MEK inhibitors were superior to conventional chemotherapy (p=0.02). Having CNS or splenic-lymphatic primary involvement tended to have a numerical but non-significant worse median OS than soft tissue or visceral disease. While female sex, size<10cm, and pMHN seemed to have numerically better OS, they did not reach statistical significance. There was no difference in median OS for age. Conclusion: This study presents updated clinicopathologic data from a pooled cohort of patients with MHN. It identifies BM involvement, stage, extent of the disease, the inflammatory background status, occurrence of HPS, and treatment approach as critical determinants of OS. Citation Format: Philip A. Haddad, Dinesh Keerty. Clinicopathologic determinants of survival in malignant histiocytic neoplasms: 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 3835.