Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster II
Methods: inclusion criteria in GFM AZAVOR study (NCT 01748240) were: 1/ IPSS int 2 or high risk MDS at the time of initiation of AZA 2/ treatment with at least 6 cycles of AZA and either failure to achieve any response or loss of response (per IWG2006 criteria) 3/ a maximum of 3 months between AZA failure and inclusion with no other treatment in between. Patients received VOR 300mg bid from day 3 to day 9 of each cycle. AZA was given at standard 75mg/m2/d day 1 to 7 or at the maximum previously tolerated dose in case of dose reduction. Patients were evaluated after 6 cycles and responding patients treated until progression. The trial used a two-stage design, and accrual was to be stopped if less than 3 responses were seen in the first 14 evaluable patients.
Results 21 patients were included between march 2013 and September 2014. Nineteen patients were treated (1 patient died and 1 progressed before treatment). Median age was 72 years. All pts had higher risk MDS and had received a median of 6 cycles of AZA before entering the trial. The median number of AZA+ VOR cycles administered was 3 (range: 1-12). No unexpected SAEs were seen, and the most common AEs were infection, thrombocytopenia, GI toxicities, and fatigue. After 6 cycles of treatment, only 2 patients (11%) achieved response (1 erythroid hematological improvement, 1 partial remission), , which, per protocol, triggered the stop of accrual. At last follow-up, 18 patients were off study and one patient was still on treatment. Nine patients stopped treatment because of progression (42%), 4 stopped treatment for lack of response (21%), 2 stopped treatment because of intolerance (11%), 1 patient stopped at his request (5%), and 1 patient died of complications of cytopenias while on treatment (5%). Median overall survival was 13 months.
Conclusion This is the first report of an add-on study in high risk MDS, a strategy that may be useful for the early evaluation of drugs for which synergy with AZA is expected. Our results show that the proposed regimen of AZA +VOR can be used safely. However, the observed response rate was not above the “background” response rate expected from AZA alone continuation in a comparable patient population, indicating that the addition of VOR cannot reverse resistance to AZA.
Disclosures: Prebet: CELGENE: Research Funding . Off Label Use: lenalidomide. Wattel: Janssen: Consultancy , Honoraria , Research Funding ; PIERRE FABRE MEDICAMENTS: Research Funding ; CELGENE: Research Funding , Speakers Bureau ; NOVARTIS: Research Funding , Speakers Bureau ; AMGEN: Consultancy , Research Funding . Cony-Makhoul: Novartis: Consultancy , Honoraria , Speakers Bureau ; BMS: Consultancy , Honoraria , Speakers Bureau . Fenaux: Amgen: Honoraria , Research Funding ; Novartis: Honoraria , Research Funding ; Janssen: Honoraria , Research Funding ; Celgene Corporation: Honoraria , Research Funding . Vey: Janssen: Honoraria ; Roche: Honoraria ; Celgene: Honoraria .
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