Real-World Use Patterns and Clinical Outcomes for Myelodysplastic Syndrome Patients Initiating Oral Decitabine and Cedazuridine or Intravenous/Subcutaneous Hypomethylating Agents
Authors: Zeidan Amer M. , Zhao Ruizhi , Pierre-Victor Dudith , Wang Yuexi , Tepsick Jon , Lan Ziyu , Salimi Tehseen 
Published: December 2024

Introduction: Decitabine and cedazuridine (DEC-C), an oral hypomethylating agent (HMA), was approved for the treatment of adult patients with myelodysplastic syndromes (MDS) in July 2020 in the USA. DEC-C is the only oral HMA approved for MDS; the other two HMAs approved for MDS, decitabine and azacitidine, are administered intravenously (IV) or subcutaneously (SC). This study aimed to examine real-world treatment outcomes among MDS patients treated with oral DEC-C compared to IV/SC HMAs using the ConcertAI real-world electronic health records database.
Methods: Patients aged 18 years and older diagnosed with MDS (based on ICD-10 code: D46*) and treated with HMAs as first treatment on or after July 1, 2020 post initial MDS diagnosis in ConcertAI's RWD360™ dataset linked to open claims were included in the study. The primary outcome was real-world overall survival (rwOS), and secondary outcomes included acute myeloid leukemia (AML)-free survival (defined as time from index HMA to AML transformation or death), and time to next treatment (rwTTNT). Kaplan-Meier survival analysis methods and Cox regression analysis were utilized to evaluate rwOS, AML-free survival, and rwTTNT among patients treated with oral DEC-C compared to IV/SC HMAs. Patient demographic (age, race, gender, region) and clinical characteristics (comorbidity index score, ECOG, body mass index, high-risk MDS based on diagnosis code, prior HMA use, and pre-MDS conditions which included anemia, thrombocytopenia, leukopenia, and neutropenia) were adjusted in the Cox models.
Results: A total of 2,101 patients with MDS were treated with HMAs as first treatment post MDS diagnosis, with 405 treated with oral DEC-C and 1,696 treated with IV/SC HMA. Of those treated with IV/SC HMA, 1,250 received azacitidine and 446 received decitabine. The overall cohort had a median age of 75 years at the start of index HMA, 73.3% White, 64.4% male, 63.4% pre-MDS conditions, 5.3% prior HMA use, 44.5% ECOG 0-1 at index HMA, 20.4% high-risk MDS, and 11.6 months median follow-up from index HMA treatment. Baseline demographic and clinical characteristics were comparable between the oral DEC-C and the IV/SC HMA cohorts. The median rwOS for the overall sample was 19.3 months, and patients who received oral DEC-C had numerically longer median rwOS compared to those treated with IV/SC HMAs (23.2 vs. 19.0 months), but this difference was not statistically significant (p=0.235). After adjusting for demographic and clinical characteristics, mortality risk for patients treated with DEC-C was slightly lower though not statistically significantly different compared to IV/SC HMAs (hazard ratio [HR]=0.94; 95% confidence interval [CI]: 0.80-1.11, p=0.442).The median AML-free survival was 13.7 months overall, and the DEC-C cohort had a significantly longer AML-free survival compared to the IV/SC HMA cohort (16.5 vs. 13.3 months, p=0.009). Patients treated with oral DEC-C had a 16% lower risk of AML transformation or death (HR=0.84; 95% CI: 0.73-0.98; p=0.027) compared to those treated with IV/SC HMAs in the adjusted model. The median rwTTNT was 7.8 months for overall, 9.4 months for the oral DEC-C, and 7.4 months for the IV/SC HMA cohort, respectively (p&lt;0.001). Patients treated with oral DEC-C were 18% less likely to receive a next treatment (HR=0.82; 95% CI: 0.71-0.94; p=0.004) compared to those treated with IV/SC HMAs in the adjusted model.
Conclusions: This real-world study is among the first and largest to date that examines clinical outcomes among MDS patients who initiated treatment with oral DEC-C compared to IV/SC HMAs. While study results indicate comparable rwOS among patients treated with oral DEC-C as those treated with IV/SC HMAs, patients treated with oral DEC-C appeared to have a significantly longer AML-free survival and rwTTNT. These findings support consideration of oral DEC-C as an alternative to parenteral HMA therapy.