Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome without Hematopoietic Cell Transplantation in a Real-World Population in the United States: Patient Characteristics, Prior Treatment Patterns, and Time to Diagnosis

Introduction: Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a rare form of hepatic injury where liver veins are blocked by damaged endothelial cells (Hildebrandt GC, et al. Br J Haematol. 2020;190:508-19). It is often associated with chemotherapy and radiation therapy given before a hematopoietic cell transplantation (HCT) but may occur outside of the HCT setting (Richardson PG, et al. Expert Rev Clin Pharm. 2018;11:113-24). The most severe form of VOD/SOS is associated with multiorgan dysfunction/multiorgan failure (MOD/MOF) and has a mortality rate of >80% if untreated (Coppell JA, et al. Biol Blood Marrow Transplant. 2018:53:138-45). This study describes the characteristics of VOD/SOS that occurs outside of the HCT setting (non-HCT VOD/SOS) in patients in the United States (US). Methods: This retrospective real-world evidence (RWE) study identified patient records within the TriNetX Dataworks US Network Electronic Medical Records (EMR) database, which covers 67 million patients from 44 healthcare organizations. Inclusion criteria required that patients had ≥1 record of a VOD/SOS diagnosis (ICD-10 code: K76.5) between January 1, 2016 and December 31, 2020, had received ≥1 instance of chemotherapy, antibody drug conjugates (ADC), or radiotherapy within 100 days prior to their first recorded VOD/SOS diagnosis, and had no record of HCT during the study period. Patient demographics and clinical characteristics, prior treatment regimen, and time to VOD/SOS diagnosis were characterized using descriptive statistics. Index treatment was defined as the treatment taken in the 100 days prior to VOD/SOS diagnosis, determined by the following hierarchy list of therapies: radiotherapy, gemtuzumab ozogamicin (GO)/inotuzumab ozogamicin (INO), vincristine, cytarabine, oxaliplatin-based, thioguanine, cyclophosphamide, 5-fluorouracil-based, etoposide, daunorubicin, doxorubicin, PEG-L-asparaginase, fludarabine, actinomycin-D, and other chemotherapies. Results: Of the 67 million patients available in the TriNetX database, 614 patients had documented VOD/SOS during the study period. Of those, 542 had ≥1 record in the EMR prior to the first VOD/SOS diagnosis. Among these 542 cases, 419 (77%) were non-HCT-related (did not have a record of HCT in the entire study period); the other 123 (23%) had a record of HCT (Figure 1). Of the 419 non-HCT VOD/SOS patients, 183 (44%) had ≥1 record of chemotherapy, ADC, or radiotherapy within the 100 days prior to first VOD/SOS diagnosis and comprised the study population. Among those 183 patients, 73 (40%) had a diagnosis of MOD/MOF at the same time VOD/SOS was documented; 61 (33%) were pediatric patients (≤16 years of age). Hematologic malignancies were the most common underlying condition (Table 1). A few patients had prior treatment with GO or INO (1% and 3%, respectively). The top 5 most common chemotherapies administered included cytarabine (25%), cyclophosphamide (20%), vincristine (17%), fludarabine (12%), and doxorubicin (11%). Overall, 103 (56%) non-HCT patients had a VOD/SOS diagnosis ≤21 days from index treatment. The median time from index treatment to VOD/SOS diagnosis was 13 days (interquartile range [IQR]: 1, 43 days) among all 183 patients. Among patients without MOD/MOF, median time was 18 days (IQR: 2, 44 days) and among patients with MOD/MOF, median time was 9 days (IQR: 0, 34 days). Conclusions: In this retrospective RWE study, the number of patients diagnosed with VOD/SOS outside of the HCT setting was approximately 3 times higher than those diagnosed in the HCT setting. Less than half of the patients diagnosed with non-HCT VOD/SOS had prior chemotherapy, ADC, or radiotherapy. Many of the non-HCT VOD/SOS patients were diagnosed with MOD/MOF. Among patients with non-HCT VOD/SOS, approximately half received their last dose of chemotherapy/ADC/radiotherapy >21 days before VOD/SOS diagnosis. Study limitations included those inherent to a retrospective study, the absence of availability of chemotherapy dosing in the database, and inability to detect misdiagnosis or under-diagnosis of VOD/SOS (which may result in under-estimation of the true number of VOD/SOS cases). The unexpected, relatively high number of VOD/SOS cases in the non-HCT setting, compared to the post-HCT setting, demonstrates a substantial unmet need, as there is no VOD/SOS treatment currently indicated for these patients. Figure 1 Figure 1. Disclosures Wang: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Benettaib: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Ni: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Jin: TriNetX: Current Employment. Kuranz: Apellis Pharmaceuticals, Inc.: Other: Payments from Apellis Pharmaceuticals to my institution TriNetX; TriNetX: Current Employment. Amber: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Ben-Joseph: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.