Maintenance Low Dose 13 Cis-Retinoic Acid and Alpha Tocopherol Improves Survival Compared to High Dose Therapy for 6 Months In LOW and INT-1/2 Stage MDS: Role for Prevention Trial
Authors: Besa Emmanuel C. , Vadakara Joseph 
Published: October 2019

Abstract
Abstract 5053
There are no current therapies or preventative strategies other than transfusion support and possibly growth factor support for the management of low risk and INT 1 Myelodysplasia. There have been a few studies that looked into the effect of 13 cis-retinoic acid (13CRA) by itself and in combination with other drugs that showed some benefits to the use of 13CRA in MDS. A randomized blinded study failed to show any benefit of 13CRA over placebo; however in this study many of the patients discontinued therapy due to side effects of the 13CRA and significant number of the patients had advanced stage disease and either had CMML, RAEB, and RAEB-t based on the classification in use then. Other studies have suggested that the beneficial effect of 13CRA is possibly seen in early stage disease and in low risk Refractory Anemia patients.
To look into the benefit that 13CRA might have on IPSS low risk, INT-1 and INT-2 MDS patients we conducted a retrospective study that looked at the effect of 13CRA given in two different doses and durations.

Methods:
This was a retrospective study that looked at patients with IPSS low risk and INT-1 and INT-2. The patients were divided into two groups. One group was treated with a dose of 13CRA at a dose of 100mg/m2/day for 6 months. The second cohort was treated with a dose of 40mg of 13CRA until disease progression. Disease progression was then compared in the two groups to see if there was any statistical difference in the treatment arms. One of the patients did not seem to have any side effects of 13CRA and it was later found that that patient was on alpha tocopherol, once this was realized then all the patients were given Alpha tocopherol (AT) at a dose 800mg per day along with 13CRA.

Results:
Twenty patients were identified in the high dose short term arm, and 29 patients in the low dose long term arm.
Both groups were similar in age (mean, range) in years, male/female ratio, duration from diagnosis to treatment. IPSS scores and transfusion requirements were comparable. Responses were observed in both groups with an overall response rate of 44.8% in HDST and 75% in LDLT with similar, low AML transformation in INT-1-2 patients of 15% in LDLT and 13.7% in HDST. A better median survival was observed with 5 patients still alive at 72 months in LDLT compared to 30 months in HDST group with a difference of 42 months (3.5 years) (Log-rank p value= 0.0099). The patients who were on the LDLT arm with alpha tocopherol had a much better toxicity profile with only 5% developing skin toxicity compared to as high as 27% in HDST arm and 100% in patients who only received 13CRA, similarly triglyceride changes were seen in 5%, 20%, and 52% respectively, AST elevations were seen in 0%, 2% and 19 % respectively.
This suggest that lack of toxicity and good tolerance using 13 CRA at 40 mg/d with 800 mg of AT for long term preventive measure in early phase MDS may result in prolonged survival and may be used as basis for a prospective prevention trial.

Disclosures:
Off Label Use: 13 cis retinoic acid is used off label.