T-Cell Lymphoma Associated Hemophagocytic Lymphohistiocytosis Has Worse Survival When Compared to T-Cell Lymphoma: A Retrospective Analysis from a Single Tertiary Center

Background: T- Cell Lymphoma (TCL) is a rare malignancy that may present with a hyperinflammatory state that resembles hemophagocytic lymphohistiocytosis (HLH), a disease characterized by hyperactive macrophages and T-cells. Patients (Pts) with TCL are known to develop lymphoma-associated HLH (LA-HLH), making distinguishing the two challenging. Pts with LA-HLH also tend to have worse prognoses, making identification crucial. While both diseases are characterized by hyperinflammation, differences between cytokines and other laboratory data may exist. Differences may be implemented into scoring systems, such as the endothelial activation and stress index (EASIX) or the optimized HLH inflammatory (OHI) index to further distinguish the two groups.

Methodology: This single-center retrospective study included pts with TCL or LA-HLH treated at MD Anderson Cancer Center. Cytokine data was collected at various time points throughout treatment. Patients in the TCL cohort did not develop LA-HLH at any point; patients with LA-HLH had cytokine data collected following their diagnosis of LA-HLH. Analyses for these laboratory values of interest along with EASIX and OHI scoring systems were conducted. The EASIX score was calculated by (LDH × creatinine/thrombocytes), and patients were determined to be OHI positive if they had CD25 >3900 U/mL and ferritin >1000 ng/mL. Kaplan-Meier curves were used to compare median survival times between the patient cohorts with a significance threshold p-value of 0.05.

Results: We evaluated61 pts with TCL and 103 pts with LA-HLH. Pts with TCL were predominantly white (74%) and male (66%); pts with LA-HLH were also predominantly white (66%) and male (55%). At the time of diagnosis, 29% of pts with TCL had marrow involvement and 61% had extranodal disease; of the pts with HLH, 33% had marrow involvement and 73% had extranodal disease. Forty nine percent of pts with LA-HLH had the T-Cell Subtype. Of these pts, 29% were classified as PTCL, 16% were MF or Cutaneous, 14% were anaplastic large cell lymphoma (ALCL), 14% were cytotoxic NK/TCL (NKTCL), and 8% were AITL. Of pts with TCL 36% were classified as PTCL, 21% had AITL, 11% had MF or cutaneous, 8% had ALCL, and 5% had NKTCL.

Pts with LA-HLH, when compared to TCL, had lower WBC, lower ANC, lower ALC, higher ALT, lower Hb, and lower PLT (P <0.005). Pts with LA-HLH, when compared to TCL had higher LDH, and Beta-2 Microglobulin, and Ferritin (P = 0.000). Cytokine values for Pts with LA-HLH demonstrated significantly elevated IL-10 (P <0.002), IL2R CD25 (P =0.000), IL-13 (P <0.049), Interferon-Y (P < 0.028), Tumor Necrosis Factor (P = 0.005) and IL-6 (P = 0.005) when compared to TCL. Principle component analysis demonstrated distinct clustering in Pts with TCL when compared to LA-HLH despite an overlap. Correlation Scatter plots in Pts with TCL correlate IL6 and IL2 Soluble Receptor, IL-6 and IL-10, and IL6 and Tumor Necrosis Factor, whereas Pts with LA-HLH correlate TNF and IL-10. Aggregated heatmap showed prominently elevated IL2 in both LA-HLH and TCL, with IL2 soluble receptor much higher in LA-HLH than in TCL. Pts with HLH also demonstrated prominently elevated LDH and decreased platelet; whereas Pts with TCL had normal LDH and normal/increased platelets. Pts with LA-HLH had elevated EASIX scores when compared to Pts with TCL (P = 0.001); Pts with LA-HLH had a greater proportion of Pts with OHI + (P = 0.000). Pts with positive OHI status also had higher quartiles of EASIX scores. Pts with LA-HLH had worse median survival when compared to TCL (5.98 months vs. 149.93, P< 0.000). Pts with TCL LA-HLH had lower median survival compared to TCL (4.27 months vs. 149.93, P < 0.000). 60-day mortality was significantly higher in pts with T-Cell LA-HLH when compared to TCL (31.31% vs. 1.85%, P =0.00)

Conclusions: LA-HLH and T-Cell LA-HLH harbor worse outcomes when compared to TCL. Significant cytokine differences exist between LA-HLH and TCL, which may help distinguish the two. Furthermore, scoring differences, such as OHI and EASIX, are pertinent and should be considered when managing these pts. Additional analyses, including treatment-related outcomes, are ongoing and will be presented at ASH 2024.

Ahmed:Myeloid Therapeutics: Consultancy; Merck: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Nektar: Research Funding; Bristol Myers Squibb: Research Funding; Xencor: Research Funding; Janssen: Research Funding; ADC Therapeutics: Consultancy. Chihara:BMS: Research Funding; MorPhosys: Research Funding; Ono pharmaceutical: Research Funding; Genmab: Research Funding; SymBio pharmaceutical: Honoraria; BeiGene: Honoraria. Lee:Curio: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Oncternal: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; MJH: Honoraria. Westin:Kite/Gilead: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Allogene: Consultancy, Research Funding; Pfizer: Consultancy; Regeneron: Consultancy; Nurix: Consultancy, Research Funding; Morphosys/Incyte: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; AbbVie/GenMab: Consultancy. Patel:BMS: Consultancy, Other: chair of scientific advisory board ; Johnson & Johnson (Janssen): Consultancy; AstraZeneca: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Pfizer: Consultancy; Abbvie: Consultancy; Takeda: Consultancy; Genentech: Consultancy; Merck: Consultancy; Caribou Sciences: Consultancy; Sanofi: Consultancy; Poseida: Consultancy; Oricel: Consultancy, Other: Chair of scientific board. Fayad:M.D. Anderson Cancer Center: Current Employment; Roche/Genentech: Research Funding. Malpica:Dizal: Research Funding; Eisai: Research Funding. Wang:Pepromene Oncology: Consultancy; Juno Therapeutics: Research Funding; Praxel: Consultancy; Oncternal: Consultancy, Research Funding; Miltenyi Biomedicine: Consultancy; Lilly: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; InnoCare: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Deciphera: Consultancy; bE Biopharma: Consultancy; Amphista Therapeutics Limited: Consultancy; ADC Therapeutics: Consultancy; WedMD: Honoraria; South African Clinical Hematology Society: Honoraria; Studio ER Congressi: Honoraria; Scripps: Honoraria; Research to Practice: Honoraria; Physicians Education Resources: Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Nurix: Honoraria; NIH: Honoraria; MSC National Research Institute of Oncology: Honoraria; Merck: Consultancy, Honoraria; MJH Life Sciences: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Genmab: Honoraria, Research Funding; Dava Oncology: Honoraria; Catamount Medical Education: Honoraria; CAHON: Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; BioInvent: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Strati:TG Therapeutics: Consultancy; Hutchison MediPharma: Consultancy; Ipsen: Consultancy; ALX Oncology: Research Funding; Roche-Genentech: Consultancy; Kite, a Gilead company: Consultancy, Research Funding; Sobi ADC Therapeutics: Consultancy, Other: Travel, accommodations, expenses, Research Funding; Acerta-Astrazeneca: Consultancy, Research Funding; Abbvie-Genmab: Consultancy. Neelapu:Anthenex: Consultancy; Adicet Bio: Consultancy, Research Funding; Appia Bio: Consultancy; Allogene: Consultancy, Research Funding; Astellas Pharma: Consultancy; Athenex: Consultancy; bluebird bio: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Caribou Biosciences: Consultancy; Carsgen: Consultancy; Chimagen: Consultancy; Fosun Kite: Consultancy; ImmunoACT: Consultancy; Incyte: Consultancy; Janssen: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Merck: Consultancy; MorphoSys: Consultancy; Orna Therapeutics: Consultancy; Sana Biotechnology: Consultancy, Research Funding; Sellas Life Sciences: Consultancy; GlaxoSmithKline: Consultancy; Synthekine: Consultancy; Takeda: Consultancy; Precision Biosciences: Research Funding; Cargo Therapeutics: Research Funding; Longbow Immunotherapy: Current holder of stock options in a privately-held company. Flowers:TG Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; BeiGene: Consultancy; Denovo Biopharma: Consultancy; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Genentech/Roche: Consultancy, Research Funding; Pharmacyclics: Research Funding; Takeda: Research Funding; Sanofi: Research Funding; 4D: Research Funding; Acerta: Research Funding; Adaptimmune: Research Funding; Allogene: Research Funding; Xencor: Research Funding; Genmab: Consultancy; Spectrum: Consultancy; Seagen: Consultancy; Pharmacyclics / Janssen: Consultancy; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; Karyopharm: Consultancy; Gilead: Consultancy, Research Funding; Amgen: Research Funding; Cellectis: Research Funding; Guardant: Research Funding; Iovance: Research Funding; Janssen Pharmaceuticals: Research Funding; Kite: Research Funding; Morphosys: Research Funding; Nektar: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Ziopharm National Cancer Institute: Research Funding; Burroughs Wellcome Fund: Research Funding; EMD Serono: Research Funding; Eastern Cooperative Oncology Group: Research Funding; BostonGene: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; AstraZeneca: Consultancy; Bio Ascend: Consultancy; Bristol Myers Squibb: Consultancy; Bayer: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding. Iyer:Innate: Research Funding; Acrotech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; Ono: Research Funding; Crispr: Membership on an entity's Board of Directors or advisory committees, Research Funding; Salarius: Consultancy; IMPaRT.AI: Other: Stock, Founder; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Yingli: Membership on an entity's Board of Directors or advisory committees, Research Funding; Legend: Research Funding; Seagen/Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Astra Zeneca: Research Funding; JCO-CCI: Other: Editor.