The presentation of human immunodeficiency virus (HIV)-associated Hodgkin lymphoma can differ from that of the general population. More specifically, primary bone marrow Hodgkin lymphoma is an uncommon presentation that is more often reported in patients with HIV. Given the many overlapping symptoms of Hodgkin lymphoma and HIV as well as HIV-associated infections, diagnosis can be difficult and delayed. We describe a case of primary bone marrow HIV-associated Hodgkin lymphoma complicated by hemophagocytic lymphohistiocytosis (HLH) where the initial work-up was inconclusive. Our case demonstrates the importance of early consideration of HLH as well as the need for an early bone marrow biopsy in a cytopenic patient with a fever of unknown origin.

Introduction: Molecular genotyping of metastatic NSCLC adenocarcinoma subtypes using next generation sequencing (NGS) is currently the standard practice. However, there is limited data on the biological predisposition to site of metastasis in patients with NSCLC based on their molecular profiling. We sought to identify any association between metastatic site and molecular profile in NSCLC patients. Method: This is a retrospective analysis conducted at UTHealth Houston/Memorial Hermann Cancer Center from January 2014 to June 2022. Clinical characteristics, pathology, NGS panel reports, and imaging were retrieved and reviewed. The χ2 test was used for categorical variables. Continuous variables were compared using Kruskal-Wallis one-way analysis of variance. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier test. Results: After excluding patients who did not have complete clinical data, a total of 143 patients were included, and their NGS panels analyzed. Median age was 65 years, with an equal number of men (n=71) and women (n=72). The most common histology was adenocarcinoma (81.8%), followed by squamous cell cancer (11.9%) and large cell carcinoma (3.5%). At least one genetic mutation was discovered in 100 patients. Mutations with a targetable drug were found in 86 patients, and many patients had >1 genetic mutation. The most common mutations were TP53 (25.2%), EGFR (24.5%), KRAS/NRAS (20.3%), and CDKN2A/2B (7.7%). Patients with any mutation were significantly more likely to have metastatic disease to the brain (57% vs 37%, p=0.03), but there was no difference in metastatic disease to bone (34% vs 26%, p=0.32). Patients without a discoverable mutation were significantly more likely to have metastatic disease to other sites (e.g., adrenal gland, liver; 91% vs 66%, p=0.002). There was no difference in PFS or OS between those with versus without mutations. Median PFS was significantly longer in patients with EGFR mutation than those with KRAS/NRAS or TP53 mutations (36 vs 16.2 vs 11.9 months, p=0.03). Median OS for patients with EGFR mutation was not reached and was significantly longer than in patients with TP53 (28.7 months) or KRAS/NRAS (26 months) mutations (p=0.003).Patients with PDL-1 >1% or TP53 were significantly more likely to have metastatic disease to organs other than bone or brain (p=0.047 and p=0.023, respectively). There was also no difference between rates of brain and bone metastasis with regards to mutational profile. Conclusion: Metastatic lung cancer patients with discoverable mutations on NGS are more likely to have metastatic disease to the brain. PDL-1 expression and TP53 mutation tend to lead to disease metastatic to organs other than brain or bone. Patients with EGFR mutations, despite having a great propensity to brain metastasis, have significantly better PFS and OS than patients with KRAS/NRAS and TP53 mutations, likely due to targeted therapy options. Citation Format: Kok Hoe Chan, Ji Lin, Arthi Sridhar, Syed H. Jafri. Genomic profiling and sites of metastasis in non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6742.

e18776 Background: The development of mutation-directed therapy and immunotherapy has revolutionized the treatment of NSCLC. We investigated outcomes of patients with or without actionable mutations (AM) in relation to their PDL-1 status. Methods: This was a retrospective analysis of patients with stage IV NSCLC from 01/2014 to 06/2022 at our institution. Four groups were identified: P0M0 (PDL-1 <1% and no AM), P0M1 (PDL-1 <1% with AM), P1M0 (PDL-1 ≥1% and no AM), and P1M1 (PDL-1 ≥1% with AM). X2 and Wilcoxon rank-rum test were used to assess categorical and continuous data, respectively. Progression-free survival (PFS) and overall survival (OS) were compared between groups using the Cox proportional-hazards model. Results: A total of 117 patients were included. Median age was 65 years, and 63 (54%) were male. The most common histology was adenocarcinoma (79%), followed by squamous cell cancer (14%) and large cell carcinoma (4%). The most common AM was KRAS (22%), followed by EGFR (21%), MET (4%), and HER2 (4%). The median PFS and OS of the entire group were 11.8 and 33.5 months, respectively. Adenocarcinomas had a higher incidence of harboring an AM (62%, p<0.0001). When comparing the PFS and OS with regard to PDL-1 and an actionable mutation, 4 prognostic groups were identified (Table). The P0M0 subgroup (n=24) had the worst median PFS and OS (8.5 and 20.6 months). The P1M1 subgroup (n=41) had the best OS at 44.5 months. Patients in the P0M1 subgroup had a longer PFS than those in the P1M1 subgroup (25.2 vs. 13.1 months), likely due to the presence of more EGFR mutations (57% vs. 32%, p=0.05). However, this did not translate into improved OS (P0M1: 33.5 months, P1M1: 44.5 months, log-rank p=0.98), perhaps because of the durable long-term response to immunotherapy in patients with PDL-1 ≥1%. The results were not significant, likely due to the small sample size in each category. Conclusions: Patients with PDL-1 <1% and no AM had the worst prognosis (median OS, 20 months). Patients with AM and PDL-1 ≥1% had the best OS, 44.5 months. This use of real-world data is an important addition to the existing information to predict survival outcomes of patients with stage IV NSCLC based on the current treatment paradigm. It provides important clinical information and should be corroborated in a larger study. [Table: see text]