National Institutes of Health Silver Spring, MD, United States
Marcela Ferrada1, Peter Grayson2, Lorena Wilson3, David Beck4, Wendy Goodspeed5, Ivana Darden6, Emma Groarke6, Dennis Hickstein6 and Bhavisha Patel7, 1National Institutes of Health, Bethesda, MD, 2National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, 3National Institutes of Health, Silver Spring, MD, 4New York University, New York, NY, 5National Institutes of Health (NIH), Bethesda, MD, 6NIH/NHLBI, Bethesda, MD, 7National Institutes of Health, Beltsville, MD
Background/Purpose: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described genetic disease due to mutations in UBA1 in hematopoietic stem cells. Patients with VEXAS have an overlap of inflammatory and hematologic manifestations. The disease is often refractory to treatment and associated with significant morbidity and mortality. Allogeneic Hematopoietic Stem Cell Transplant (HSCT) could be a curative treatment. We evaluated indications and eligibility for HSCT in a prospective cohort of patients with VEXAS.
Methods: Patients with genetically confirmed VEXAS from a prospective observational cohort from 2019-2022 were included. Indications for HSCT were defined based on clinical consensus as 1) hematologic abnormalities: anemia ≤ 10 g/dL or transfusion dependence to red blood cells or platelets; or 2) refractory inflammatory disease (RID) defined as prednisone requirement of ≥ 20 mg per day to control symptoms. Eligibility for HSCT was defined by specific end organ assessment and functional status. Categorical and continuous variables were compared using the chi-square test or Kruskal-Wallis test.
Results: Twenty male patients with median age at disease onset of 63 (IQR 57-66) years were studied. At initial evaluation, median disease duration was 5 (IQR 2.5-6) years, median prednisone dose was 21 (IQR 16-30) mg/day and median number of previous DMARDs used was 3 (IQR 2.5-5.5).
At first visit, 14 (70%) patients met an indication for HSCT; nine (45%) with hematologic indication, eight (40%) due to RID, and three (15%) patients met both indications. Four (20%) patients were red blood cell transfusion dependent, none were platelet transfusion dependent.
Six out of 14 patients who met indications were not eligible for HSCT due to a diagnosis of multiple myeloma n=2; Karnofsky score < 40% n=2; age ≥75 n=1; or HIV infection n=1.
Patients with RID indications for HSCT were younger at disease onset, (56 vs 64 years, p=0.01), historically received more DMARDs (5 vs 2, p< 0.01), and had lower values of ESR (5.8 vs 17 mm/hr, p=0.04) and CRP (32 vs 68 mg/L, p=0.02) at initial evaluation.
Patients were prospectively followed for a median of 9 months (IQR 3-25). Five patients did not have an indication for HSCT at the initial visit, but all of them met eligibility requirements for HSCT during subsequent visits. Two of these patients developed both hematologic and RID indications for HSCT after 6 months follow-up. Three patients with hematologic indications for HSCT during follow-up died (two due to disease progression, and one with severe COVID-19 infection).
Two patients underwent HSCT and remain off all therapy for VEXAS at 6- and 11-months post-transplant follow-up.
Conclusion: Patients with VEXAS may differentially meet indications for HSCT based on hematologic or inflammatory burden of disease. In absence of effective standard medical therapy other than high dose glucocorticoids, multidisciplinary evaluation for HSCT should be considered in every VEXAS patients but not all will qualify. Further prospective follow-up is needed to determine the right timing for HSCT intervention in subset of VEXAS patients.
Disclosures: M. Ferrada, None; P. Grayson, None; L. Wilson, None; D. Beck, None; W. Goodspeed, None; I. Darden, None; E. Groarke, None; D. Hickstein, None; B. Patel, None.
