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4604 Azacitidine for Patients with Vexas Syndrome: Data from the French Vexas Registry

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
MDS, autoimmune disorders, Research, Non-Biological therapies, Clinical Research, Genetic Disorders, Chemotherapy, Chronic Myeloid Malignancies, Immune Disorders, Diseases, Therapies, Myeloid Malignancies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Thibault Comont1*, Olivier Kosmider, MD, PhD2*, Mael Heiblig3*, Benjamin Terrier, MD, PhD4*, Didier Bouscary5*, Guillaume Le Guenno6*, Roderau Outh7*, Maxime Samson8*, Achille Aouba9*, Estibaliz Lazarro10*, Odile Rauzy1*, Lucie Rigolot11*, Pierre Peterlin12*, Alexandre Maria13*, Edouard Flammarion14*, Alice Garnier, MD15*, Benoit De Renzis16*, Shanti Natarajan17*, Benjamin Carpentier18*, Marielle Roux-Sauvat19*, Jose Torregrosa20*, Fabienne Closs-Prophette21*, Julien Rossignol22*, Nicolas Schleinitz23*, Celine Dieval24*, Jonahan Broner25*, Marie-Pierre Gourin, MD26*, Gaetan Sauvetre27*, Benoit Faucher28*, Julien Vinit29*, Sylvie Grosleron30*, Alexis Mathian31*, Louis Terriou, MD PhD32*, Cyrille Coustal33*, Philippe Guilpain34*, Paola Marianetti-Guingel35*, Holy Bezanahary36*, Norbert Vey, MD37, Bilal Mohty38*, Thomas Moulinet39*, Vincent Grobost6*, Sophie Dimicoli40*, Benoit Suzon41*, Antoinette Perlat42*, Pierre Hirsh43*, Lise Larcher44*, Lin Pierre Zhao, MD45*, Sophie Georgin-Lavialle46*, Arsene Mekinian47*, Pierre Fenaux, MD, PhD48, Vincent Jachiet47*, French VEXAS study group49*, Minhemon French Network of immune disorders associated with hemopathies49* and GFM Groupe Francophone des Myélodysplasies49*

1Toulouse University Hospital, Toulouse, France
2Cochin Hospital, Paris, FRA
3Hematology Department, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
4Department of Internal Medicine, National Referral Center for Rare and Systemic Autoimmune Diseases, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
5APHP Cochin Hospital, Paris, FRA
6Clermont-Ferrand University Hospital, Clermont-Ferrand, FRA
7Perpignan Hospital, Perpigan, France
8CHU Dijon, Dijon, FRA
10Bordeaux University Hospital, Bordeaux, France
11CHU de Toulouse - Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France
12Hematology Department, Hôpital Hotel Dieu, NANTES CEDEX 1, France
13Montpellier University Hospital, Montpellier, FRA
14AP HP, Paris, FRA
15Hematology clinic, Nantes University Hospital, Nantes, France
16Clermont Ferrand Hospital, Clermont-Ferrand, France
17C.H.U. Strasbourg Hopital Civil, Strasbourg, FRA
18Saint Vincent de Paul Hospital, Lille, FRA
20Poitiers University Hospital, Poitiers, FRA
21Le Mans Hospital, Le Mans, France
22Hématologie, NECKER ENFANTS MALADES Hospital APHP, Paris, FRA
23Marseille University Hospital AP-HM, Marseille, FRA
24Rochefort Hospital, ROCHEFORT CEDEX, FRA
25Nîmes University Hospital, Nîmes, FRA
26CHU Limoges, Limoges, FRA
27Rouen University Hospital, Rouen, FRA
28Marseille University Hospital, Marseille, France
29CHWM, Chalon sur Saône, France
30Agen Hospital, Agen, France
31Pitié-Salpêtrière Hospital, AP-HP, Paris, France
32Lille University Hospital, Lille, FRA
33Montpellier Univeristy Hospital, Montpellier, France
34Montpellier University Hospital, Montpellier, France
35Reims University Hospital, Reims, France
36Limoges University hospital, Limoges, FRA
37Department of Hematology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM, Marseille, France
38Geneva University Hospital, Geneve, CHE
39Inserm 1098, Nancy, FRA
40Bordeaux University Hospital, Pessac, FRA
41Fort de France University Hospital, Fort de France, France
42CHU Rennes, Rennes, FRA
43Saint antoine hospital APHP, Paris, France
44Hopital Saint-Louis and University De Paris, Paris, FRA
45Saint Louis hospital APHP, Paris, France
46INSERM and AP-HP, Paris, FRA
47Saint Antoine Hospital AP-HP, Paris, France
48Hôpital Saint-Louis, Hematology Department, AP-HP, Paris, France
49APHP, Paris, France


VEXAS syndrome (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome) is an an often life threatening autoinflammatory disease resulting from UBA1 gene somatic mutations, associated in 40-50% patients (pts) with MDS. While we and others found Ruxolitinib to have frequent efficacy in VEXAS (Heiblig, Blood 2022;140:927-931), we also suggested a significant role of azacitidine (AZA) in a retrospective study (n=11, Comont, Br J Haematol 2022 ;196:969-974) and a prospective study (n=12, Mekinian, Leukemia 2022 ;36:2739-2742). We report here the efficacy, safety and prognostic factors of AZA treatment in a larger cohort of VEXAS pts, most of whom had concomitant MDS.


In this retrospective study, we selected typical VEXAS pts from the French nationwide registry (n=326 pts with UBA1 mutation: Met41 or alternative splicing site) who received at least one full cycle of AZA. Major response to AZA on VEXAS was defined as (i) complete control of clinical inflammatory symptoms (ii) C-reactive protein (CRP) <10 mg/L (iii) daily steroid dosage <10 mg/day, and no other immunosuppressive treatment administered for VEXAS. Minor response referred to significant improvement, not meeting all major response criteria


57 male pts (median age 71, range 54-86, at AZA onset) with severe (clinical and/or biological) phenotype were included. 50 (88%) of them were considered to have associated MDS based on morphology in 46 (WHO 2016 criteria): MDS-MLD (n=31), MDS-EB1 (n=8), MDS-SLD (n=3), MDS-RS (n=2), MDS-EB2 (n=1) and CMML-2 (n=1), of whom 94 had normal karyotype; and based on presence of clonal cytogenetic abnormality in 4 (del 9q, +15, t(12;15), del 7q). R-IPSS was very low/low/intermediate/high in 5/24/9/6 cases respectively. NGS mutational profile before AZA, available in 44 pts, found TET2 mutation in 10 (22.7%), DNMT3A mutation in 13 (29.6%) and at least another myeloid mutation in 12 (27.2%) pts.

At AZA onset, all pts except 3 were receiving steroids, with a median dose of 20 mg/day, and median duration of steroid exposure was 21 months (range 1-173). Apart from steroids, pts had received a median of 2 immunosuppressive/modulatory drugs (range 0-8).

The median number of AZA cycles administered was 11 (range 1-111), and 27 (47%) pts had discontinued AZA at the time of analysis, due to serious infection (n=6), persisting response (n=4), primary or secondary failure (n=5), local or systemic allergic manifestations (n=4), allogeneic stem cell transplantation (n=4), unrelated causes (n=4). Two pts progressed to high-risk MDS, but none to AML. Median follow-up from AZA onset was 29 months, and 16/ 57 patients had died, 8 of whom while still on AZA. Cause of death in those 8 pts was COVID-19 (n=1), other infection (n=3), VEXAS (n=1), unrelated (n=3).

During AZA treatment, serious adverse events were reported in 30 (53%) pts, including mostly infections (n=25).

51 pts (46/50 with, and 5/7 without MDS), who received at least 3 cycles of AZA, were considered evaluable for response. A VEXAS response was achieved in 34/46 (74%) pts with MDS, major in 23 (50%). In responders, prednisone could be discontinued in 15 pts, while the remaining 19 patients received a median dose of 7 mg/day. Best response was obtained after 3-6/ 7-9/10-12/>12 cycles of AZA in 20/5/3/4 pts, respectively (2 unknown). After a median follow up of 35 months (range 5-163) from AZA onset, 21/34 (62%) were still responders.

All 5 pts without MDS achieved a major response (during 4 to 37+ months, with no relapse).

In univariate analysis on 46 MDS pts receiving at least 3 cycles of AZA (including VEXAS phenotype and MDS characteristics), no predictive factor for the response to AZA were identified.

Of the 51 pts who received at least 3 cycles of AZA, 32/41 (78%) corrected anemia (including 22/31 (71%) who achieved RBC-transfusion independence), 19/28 (68%) thrombocytopenia, and 3/6 (50%) neutropenia.

UBA1 mutation VAF monitoring during treatment, currently available in 6 responders, showed mutation negativation in 4 patients, and reduction to 89 and 62 % in 2 and more responders are being analyzed.


We confirmed the efficacy of AZA in this large cohort of VEXAS pts, even in those with no demonstrated underlying MDS, where the treatment appears to directly impact clonal evolution in at least some cases. The infectious risk, in these pts who have in particular received steroids and immunosuppressive drugs, requires close monitoring.

Disclosures: Comont: BMS: Consultancy, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria. Heiblig: Jazz Pharmaceuticals: Honoraria; AbbVie: Honoraria; Pfizer Inc.: Honoraria; Astellas: Honoraria; Servier: Honoraria. Fenaux: AbbVie: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; French MDS Group: Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

*signifies non-member of ASH