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548 Real-World Treatment Patterns Among Patients with Myelodysplastic Syndromes Initiating Oral Decitabine and Cedazuridine or Intravenous/Subcutaneous Hypomethylating Agents

Program: Oral and Poster Abstracts
Type: Oral
Session: 906. Outcomes Research – Myeloid Malignancies: Real-World Treatment Patterns and Outcomes
Hematology Disease Topics & Pathways:
MDS, Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies
Sunday, December 10, 2023: 12:15 PM

Amer M. Zeidan, MBBS, MHS1, Halley Costantino2*, Kushal Modi2*, Tehseen Salimi3*, Terri Washington3* and Robert S. Epstein4*

1Yale University and Yale Cancer Center, New Haven, CT
2Cerner Enviza, North Kansas City, MO
3Taiho Oncology, Inc., Princeton, NJ
4Epstein Health LLC, Woodcliff Lake, NJ

Introduction: Hypomethylating agents (HMAs) are recommended standard of care for patients with higher-risk myelodysplastic syndromes (HR-MDS). HMA therapies include intravenous (IV) or subcutaneous (SC) decitabine and azacitidine; however, parenteral administration of HMAs has been associated with increased patient burden. The oral HMA decitabine and cedazuridine (DEC-C) was FDA-approved in July 2020 for the treatment of MDS, and offers an alternative to IV/SC HMAs, with similar pharmacokinetic exposure and response rates compared to IV decitabine. This study examined treatment patterns among patients with MDS receiving oral DEC-C compared with IV/SC HMAs in real-world clinical practice.

Methods: This was a retrospective analysis using the US Cerner Enviza claims database; medical and prescription claims data for patients were linked to mortality data from Datavant. Adults aged ≥18 years, who were diagnosed with MDS (ICD-10-CM code D46.x; all risk levels), and who had initiated a HMA (≥1 claim; August 1, 2020─August 31, 2022) were included; index date was defined as the first pharmacy or medical claim for DEC-C or IV/SC HMAs, respectively. Patients had variable follow-up after index and were followed until end of enrollment, death, or end of study. Propensity score matching (PSM; 1:1) was performed to balance for confounding factors (age, sex, acute myeloid leukemia [AML] diagnosis, Charlson Comorbidity Index [CCI] score, and red blood cell [RBC] transfusion); adjusted bivariate analysis was used to compare outcomes between treatment groups. Longitudinal persistence was assessed according to the number of cycles of therapy received during follow-up, where a cycle was defined as either 3–10 days of administration of index IV/SC HMA or 1 claim for oral DEC-C, within a 28-day cycle.

Results: Of 1569 patients included, 160 (10.2%) received DEC-C and 1409 (89.8%) received IV/SC HMAs. In the DEC-C cohort, median age was 72.5 years and 66.9% were male; in the IV/SC cohort, median age was 69.0 years and 58.2% were male. Two-thirds of patients newly initiated HMAs during the study period (69.4% for DEC-C and 72.2% for IV/SC HMAs); 30.6% of the DEC-C cohort had switched from prior IV/SC HMA treatment. Both groups had high levels of comorbidity; 55.6% of patients in the DEC-C cohort and 58.4% in the IV/SC HMA cohort had CCI scores of ≥3, and 14.4% and 23.8%, respectively, had an AML diagnosis. During the 6-month pre-index period, half (55.3%) of patients in both groups received RBC transfusions, and one quarter (25.9%) received platelet transfusions. After matching, there were 158 patients in each treatment cohort and all covariates included in the PSM were balanced (standardized mean difference <0.2). Median age was 72.0 years and 74.0 years for the DEC-C and IV/SC HMAs matched cohorts, respectively, and 66.5% and 69.6%, respectively, were male. Mean CCI scores were 3.45 for DEC-C and 3.15 for IV/SC HMA groups and 14.6% and 15.8%, respectively, had an AML diagnosis pre index. Longitudinal persistence was comparable between the matched DEC-C and IV/SC cohorts during the first 6 months post-index, with similar proportions receiving the maximum number of treatment cycles (based on a 28-day cycle) at each month following index (73.8% vs 71.1%, 46.5% vs 48.7%, 28.6% vs 24.8%, for 2, 4, 6 months, respectively; Figure). However, a trend towards improved persistence with DEC-C versus IV/SC HMAs was observed in patients receiving treatment beyond 6 months (25.0% vs 17.0%, 18.5% vs 9.0%, 11.4% vs 7.6%, for 8, 10, 12 months, respectively). Mean time to discontinuation of treatment was also numerically higher for DEC-C compared with the IV/SC HMA group (87.7 vs 82.0 days); however, differences were not statistically significant.

Conclusions: This study, which is to our knowledge the largest real-world report of oral DEC-C use to date, reveals similar but high levels of disease burden and comorbidities among patients with MDS receiving oral DEC-C and parenteral HMA therapy. Trends in treatment patterns suggest comparable persistence with oral DEC-C and IV/SC HMAs at early stages of therapy and improved persistence with oral DEC-C beyond 6 months. These data support the consideration of oral DEC-C as an alternative to chronic parenteral HMA therapy, with the potential for oral DEC-C to reduce the treatment burden associated with administration of IV/SC HMAs.

Disclosures: Zeidan: Takeda: Consultancy, Honoraria; ALX Oncology: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Notable: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Orum: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Tyme: Consultancy, Honoraria; BeyondSpring: Consultancy, Honoraria; Schrödinger: Consultancy, Honoraria; Zentalis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Shattuck Labs: Research Funding; Astex: Research Funding; Foran: Consultancy, Research Funding; Geron: Consultancy, Honoraria; Taiho: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Ionis: Consultancy, Honoraria; Syndax: Consultancy, Honoraria; Kura: Consultancy, Honoraria; Chiesi: Consultancy, Honoraria; BioCryst: Consultancy, Honoraria; Mendus: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Syros: Consultancy, Honoraria; Lox Oncology: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Costantino: Taiho Oncology, Inc.: Other: Employee of Cerner Enviza, who received funding from Taiho Oncology, Inc. for this study. Modi: Taiho Oncology, Inc.: Other: Employee of Cerner Enviza, who received funding from Taiho Oncology, Inc. for this study. Salimi: Taiho Oncology, Inc.: Current Employment. Washington: Taiho Oncology, Inc.: Current Employment. Epstein: Tasso, Inc.: Membership on an entity's Board of Directors or advisory committees; Taiho Oncology, Inc.: Consultancy; Intra-Cellular Therapies: Consultancy; Merck: Consultancy; Otsuka: Consultancy; G1 Therapeutics: Consultancy; Janssen: Consultancy; Radius Health: Consultancy; Halozyme: Consultancy; Illumina: Membership on an entity's Board of Directors or advisory committees; Veracyte: Membership on an entity's Board of Directors or advisory committees; Diadem: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure: Oral decitabine and cedazuridine (ASTX727, DEC-C), is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups. This abstract reports a study of real-world treatment patterns and may reflect possible off-label use of DEC-C in patients outside of this indication.

*signifies non-member of ASH