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3726 The Optimized HLH Inflammatory Index Is Associated with a Higher Stage of Lymphoma, but an Unexpected High Mortality Associated with Inflammation

Program: Oral and Poster Abstracts
Session: 201. Granulocytes, Monocytes, and Macrophages: Poster III
Hematology Disease Topics & Pathways:
Research, Hodgkin lymphoma, non-Hodgkin lymphoma, Lymphomas, B Cell lymphoma, Clinical Research, T Cell lymphoma, indolent lymphoma, Diseases, aggressive lymphoma, real-world evidence, Lymphoid Malignancies
Monday, December 12, 2022, 6:00 PM-8:00 PM

Adi Zoref-Lorenz, MD1,2,3, Jun Murakami, MD/ PHD4*, Liron Hofstetter, MD5,6*, Uri Abadi, MD1*, Swaminathan P. Iyer, MD7, Shehab Fareed Mohamed, MD8,9*, Abd El Haleem Natour, MD10*, Shiri Weinstein, MD5,11*, Joanne Yacobovich, MD, MPH5,12, Shai Izraeli, MD5,12, Sarah Nikiforow, MD, PhD13, Ronit Gurion, MD5,6*, Inbar Cohen, MD6*, Oren Pasvolsky, MD5,6,14*, Pia Raanani, MD5,6, Arnon Nagler, MD5,15, Nancy Berliner, MD16, Naval Daver, MD17, Martin H. Ellis, MD1,5*, Gaurav Goyal, MD18 and Michael B Jordan, MD19,20

1Hematology Institute, Meir Medical Center, Kfar Saba, Israel
2Sackler School of Medicine, Tel Aviv University, Tel Aviv, OH, Israel
3Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Blue Ash, OH
4Clinical Laboratory, Transfusion Medicine and cell therapy, University of Toyama, Toyama, Japan
5Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
6Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
7Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
8Division of Hematology, Department of Medical Oncology, National Center for Cancer Care & Research (NCCCR), Hamad Medical Corporation (HMC), Doha, Qatar
9Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
10Internal Medicine “A,” Meir Medical Center, Kfar Saba, Israel
11Internal Medicine "D", Sheba Medical Center, Ramat Gan, Israel
12Department of Pediatric Hematology Oncology, Schneider Children Medical Center of Israel, Petach Tikva, Israel
13Dana-Farber Cancer Institute, Boston, MA
14Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
15Hematology and Bone Marrow Transplant Unit, Chaim Sheba Medical Center, Tel Hashomer, Israel
16Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA
17MD Anderson Cancer Center, Houston, TX
18Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
19Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
20Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome that may complicate hematologic malignancies (HM). We recently developed a simplified diagnostic and prognostic index termed the ‘optimized HLH inflammatory’ (OHI) index comprising the combined elevation of sCD25 (>3,900 U/mL) and ferritin (>1,000 ng/mL) in this context (Zoref-Lorenz A, Murakami J, Hofstetter L, et al. An improved index for diagnosis and mortality prediction in malignancy-associated hemophagocytic lymphohistiocytosis. Blood. 2022;139(7):1098-1110). In this study, we assessed whether OHI-positive lymphoma patients have more advanced lymphoma and whether mortality among these patients is related to lymphoma or other causes.

Methods: We performed a multicenter, retrospective study of patients with newly diagnosed lymphoma in whom sCD25 and ferritin levels were measured either as routine surveillance or during investigation for HLH and classified patients by their OHI status. Age at lymphoma diagnosis, complete blood counts, albumin, lactate dehydrogenase, Ann Arbor stage, extranodal site involvement, and ECOG performance status were documented. Overall survival at five years/last follow-up was recorded, as was the cause of death. OHI- and OHI+ patients were compared by international prognostic index (IPI), International Prognostic Score, and Follicular Lymphoma International Prognostic Index for T/B cell non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma, and follicular lymphoma, respectively. Predicted five-year overall survival was calculated based on the relevant prognostic index and was compared between OHI- and OHI+ patients. The odds ratios (ORs) for observed vs. predicted mortality was calculated using the Chi-square test. In addition, time to death by mortality cause analysis was performed.

Results: 100 lymphoma patients were studied: 63 were OHI-, and 37 were OHI+, 65% of the patients had B cell NHL, 18% had natural killer/ T cell lymphoma, and 17% had Hodgkin’s lymphoma. More than half of the patients had sCD25 and ferritin measured as routine surveillance at the time of malignancy diagnosis (57%). The disease-relevant prognostic index-predicted five-year survival did not differ between OHI- and OHI+ patients (a mean of 57% in OHI- and 58% in OHI+ p=0.62). Compared to OHI- patients, OHI+ patients had a more advanced Ann Arbor stage (p=0.014) but did not differ in the number of extranodal sites, ECOG performance, or disease-relevant IPI. The disease-relevant prognostic index-predicted 5 – year survival did not differ between OHI- and OHI+ patients (Figure 1). However, the actual 5-year survival in OHI+ patients was substantially lower than predicted (12%), reflecting a mortality incidence four times higher than predicted by standard prognostic scoring (OR 3.9; CI 1.3-12.1). By contrast, OHI- patients had better survival (79%) than predicted (Figure 1) by their prognostic scores (OR 0.15; CI 0.07-0.34). In addition, more than half of the OHI+ patients died from non-malignant causes, while most deaths among OHI- patients (92%) were from progressive malignancy. Mortality related to multi-organ failure occurred early in OHI+ patients (Figure 2).

Conclusion: OHI+ patients had a slightly more advanced lymphoma but were generally similar to OHI- patients according to their lymphoma-relevant prognostic index. However, OHI+ patients had a higher mortality rate due to infections and multi-organ failure, suggesting that the OHI index identifies a clinically important inflammatory state in lymphoma patients.

Disclosures: Zoref-Lorenz: Sobi: Consultancy. Iyer: Salarius Pharmaceuticals, Inc.: Consultancy. Nikiforow: Kite, a Gilead Compnay: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Gurion: Roche: Honoraria; Gilead: Honoraria; Medison Ltd: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Raanani: Janssen: Speakers Bureau; BMS: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Daver: Pfizer: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Arog: Consultancy; Hanmi: Consultancy, Research Funding; Trovagene: Research Funding; FATE Therapeutics: Research Funding; Novimmune: Research Funding; Glycometrics: Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Servier: Consultancy, Research Funding; Novartis: Consultancy; Trillium: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy, Research Funding; Jazz: Consultancy; Celgene: Consultancy; Syndax: Consultancy; Shattuck: Consultancy; Agios: Consultancy. Ellis: Novartis: Consultancy, Speakers Bureau; Gad Medical: Consultancy, Speakers Bureau. Goyal: 2nd.MD: Consultancy; UpToDate: Patents & Royalties; SeaGen: Research Funding; Viracta Therapeutics: Research Funding; Sutro Biopharma: Research Funding. Jordan: Sobi, Inc.: Consultancy, Research Funding.

*signifies non-member of ASH