Oral DEC-C Treatment Is Feasible in MDS

Although improved treatment persistence was observed with oral decitabine and cedazuridine (DEC-C) vs intravenous (IV)/subcutaneous (SC) standard-of-care parenteral hypomethylating agents (HMAs) beyond 6 months, oral DEC-C and HMAs were associated with similar levels of comorbidities and disease burden in patients with myelodysplastic syndrome (MDS), according to a presentation of data at the 2023 American Society of Hematology Annual Meeting.¹

According to Amer Zeidan, MBBS, during the first 6 months after filing a claim for an HMA, the proportions of patients who claimed oral DEC-C and received the maximum number of treatment cycles each month were similar to those proportions of patients who claimed IV/SC HMAs.

Amer Zeidan, MBBS

During the first 2 or more cycles in the first 2 months of treatment, 73.8% and 71.1% of patients in the oral DEC-C (n = 126) and IV/SC HMA (n = 142) arms received the maximum number of treatment cycles each month. These rates were 46.5% and 48.7%, respectively in 101 and 117 patients, during the first 4 or more cycles in the first 4 months of treatment, and 28.6% and 24.8%, respectively in 77 and 101 patients, during the first 6 or more cycles in the first 6 months of treatment.

However, investigators observed a trend toward improved persistence with oral DEC-C vs IV/SC HMAs in patients who received treatment beyond 6 months. In total, 25.0% of patients who received 8 or more cycles of oral DEC-C in the first 8 months of treatment (n = 64) received the maximum number of treatment cycles each month vs 17.0% of those in the IV/SC HMA arm (n = 88). These rates were 18.5% vs 9.0%, respectively in 54 and 78 patients, during the first 10 or more cycles in the first 10 months of treatment, and 11.4% and 7.6%, respectively in 44 and 66 patients, during the first 12 or more cycles in the first 12 months of treatment.

The mean time to treatment discontinuation was numerically higher in the oral DEC-C arm vs the IV/SC HMA arm, at 87.7 days vs 82.0 days. However, this difference was not statistically significant.

“It’s hoped that [longer persistence with oral DEC-C] would translate to better outcomes because those patients are able to stay on a treatment that takes time to work,” Zeidan, the director of Early Therapeutics Research, Hematology, and the leader of the Clinical Research Team for Leukemias and Myeloid Malignancies at Yale Cancer Center in New Haven, Connecticut, said during a presentation of the data.

IV and SC administered HMAs are underutilized in clinical practice. A retrospective analysis conducted using the 2010-2016 Surveillance, Epidemiology, and End Results–Medicare database showed that among patients aged 66 years and older with newly diagnosed refractory anemia with excess blasts (a surrogate for higher-risk MDS), 44.2% did not use HMAs.2 Furthermore, HMA non-users had more hospitalizations (mean, 0.47 vs 0.30; P < .001) and emergency room visits (mean, 0.69 vs 0.41; P = .005) per month than HMA users.

Moreover, a survey conducted among 120 adult patients (and 21 caregiver proxies) with MDS who had received HMAs within 6 months of the survey found that of the 89 patients who received IV HMAs, 74.2% and 69.7% respectively reported treatment-related interference with their social and daily activities, and 66.3% reported treatment administration–related pain.3 These values were 86.5%, 80.8%, and 94.2% among patients who received SC HMAs.

“Patients prefer oral options whenever they are available,” Zeidan noted in the presentation.¹

This real-world study used the United States Cerner Enviza claims database. Investigators linked patient medical and prescription claims data with mortality data from Datavant. The pre-index period of this trial ran from February 1, 2020, to August 1, 2020. Adults diagnosed with MDS were included in this study if they had at least 1 claim for an HMA (either oral DEC-C or an IV/SC HMA) between August 1, 2020, and August 31, 2022. Patients’ index dates were defined as the dates of their first claim for an HMA. As patients had variable follow-ups after their respective index dates, they were followed until loss to follow-up, death, or the end of the study.

In total, 1569 patients received treatment with HMAs during the study’s patient selection period; 160 patients received oral DEC-C, and 1409 patients received IV/SC HMAs. Investigators performed a propensity score matching (PSM) analysis in a 1:1 fashion to balance for confounding factors, including age, sex, acute myeloid leukemia (AML) diagnosis, Charlson Comorbidity Index (CCI) score, and red blood cell (RBC) transfusions. In this PSM, 158 patients who had received oral DEC-C were paired with 158 best matches among patients who had received IV/SC HMAs.

After PSM, investigators assessed longitudinal persistence according to the number of cycles of therapy patients received during follow-up. Within a 28-day cycle period, investigators defined 1 cycle as 3 to 10 days of the administration of the indexed IV/SC HMA or 1 claim for oral DEC-C. Investigators also used a Kaplan-Meier analysis to estimate the time to treatment discontinuation across cohorts.

In the oral DEC-C arm, patients had a median age of 72.0 years (range, 29-90), and 66.5% were male. Insurance types consisted of commercial (37.3%), Medicare Advantage (45.6%), Medicaid (14.6%), and unknown/other (2.5%). The mean CCI score in this arm was 3.5 (standard deviation, 3.0), and 55.7% of patients had a mean CCI score of 3 or higher. At pre-index, 14.6% of patients had an AML diagnosis, and 58.9% and 24.1% of patients received RBC and platelet transfusions, respectively.

In the IV/SC HMA arm, patients had a median age of 74.0 years (range, 27-90), and 69.6% were male. Insurance types consisted of Medicare Advantage (46.2%), commercial (27.9%), Medicaid (25.3%), and unknown/other (0.6%). The mean CCI score in this arm was 3.2 (standard deviation, 2.8), and 52.5% of patients had a mean CCI score of 3 or higher. At pre-index, 15.8% of patients had an AML diagnosis, and 48.1% and 20.9% of patients received RBC and platelet transfusions, respectively.

Regarding pre-index HMA use among the matched cohorts, in the oral DEC-C arm, 30.4% of patients had received prior HMAs, all of whom had switched from prior IV/SC HMA treatment. Additionally, 69.6% of patients in the oral DEC-C arm were HMA naive and initiated an HMA for the first time during the study period. In the IV/SC HMA arm, 29.1% of patients had received prior HMAs, and 70.9% of patients were HMA naive.

Limitations of this study included the lack of generalizability of these findings to patient populations including younger patients or patients without health insurance coverage, and the small sample sizes of the cohorts, which limited cross-cohort comparisons, particularly at later time points. Furthermore, the study inclusion criteria and reporting did not differentiate between higher- and lower-risk MDS patient groups, although most patients likely had higher-risk disease based on the treatment they received.

Zeidan noted that next steps for this analysis include evaluating patient outcomes regarding survival. A registry trial is planned to observe patient outcomes that cannot be observed in databases, such as CR rates.

“These data, in conjunction with the patient survey data reporting high treatment satisfaction and improvements in quality of life with oral DEC-C, support the consideration of oral DEC-C as an alternative to chronic parenteral HMA therapy, with the potential to reduce the treatment burden associated with administration of IV/SC HMAs,” the study authors wrote in the presentation.

^References

^{1. Zeidan AM, Costantino H, Modi K, et al. Real-world treatment patterns among patients with myelodysplastic syndromes initiating oral decitabine and cedazuridine or intravenous/subcutaneous hypomethylating agents. Blood. 2023;142(suppl 1):548. doi:10.1182/blood-2023-188638}

^{2. Zeidan AM, Joshi N, Kale H, et al. Impact of hypomethylating agent use on hospital and emergency room visits, and predictors of early discontinuation in patients with higher-risk myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk. 2022;22(9):670-679. doi:10.1016/j.clml.2022.04.016}

^{3. Zeidan AM, Jayade S, Schmier J, et al. Injectable hypomethylating agents for management of myelodysplastic syndromes: patients’ perspectives on treatment. Clin Lymphoma Myeloma Leuk. 2022;22(3):e185-e198. doi:10.1016/j.clml.2021.09.009}