Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Effectiveness study (incl. comparative)

Data collection methods

Secondary data collection
Non-interventional study

Non-interventional study design

Cohort
Other

Non-interventional study design, other

Retrospective study
Study drug and medical condition

Study drug International non-proprietary name (INN) or common name

AZACITIDINE

Medical condition to be studied

Myelodysplastic syndrome
Population studied

Short description of the study population

Patients aged 18 years or older receiving treatment with azacitidine for documented histological diagnosis of myelodysplastic syndrome (MDS) as per medical record documentation in the electronic health record (EHR) identified from the United States Oncology Network (USON) database between t between 01 January 2014 through 01 January 2020.
Inclusion Criteria:
1) Male or female ≥ 18 years of age.
2) Documented histological diagnosis of MDS defined as per medical record documentation in the EHR.
3) Documented Revised International Prognostic Scoring System (IPSS-R) MDS risk category of intermediate-, high-, or very high-risk.
4) Initiation of AZA monotherapy during the Study Index Period.
5) Received at least a single dose of treatment with AZA in line with US Prescribing information; the following dosing regimens were permitted:
a) AZA 75 mg/m2 on Days 1-7 of a monthly cycle.
b) AZA 75 mg/m2 on Days 1-5, 8-9 of a monthly cycle (5 days on, 2 days off on the weekend, 2 days on).
c) AZA 75 mg/m2 on Days 1-5 of a monthly cycle
6) Patients should not have received any antileukemic therapies for the treatment of MDS prior to the initiation of AZA. (Prior and concurrent therapy with hydroxyurea, oral etoposide, erythroid and/or myeloid growth factors, or any symptomatic treatment was allowed. Patients with MDS who received prior anticancer therapy from prior malignancies were permitted).
7) Patients had to have at least 1 posttreatment encounter in the EHR.
8) White blood cell (WBC) count ≤ 20 × 103/µL at the time of AZA initiation (use of hydroxyurea to reduce WBC prior to AZA initiation, as documented within the EHR was acceptable).
9) Adequate hepatic and renal function at the time of AZA initiation (within 30 days of index) as evidenced by the following documentation in the EHR: a) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal (ULN).
b) Bilirubin ≤ 1.5 × ULN, or 3.0 × ULN and primarily unconjugated if patient had a documented history of Gilbert’s syndrome or genetic equivalent.
c) Serum creatinine ≤ 1.5 × ULN or calculated glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m2

Exclusion Criteria:
1) Any prior antileukemic therapy including chemotherapy (excluding hydroxyurea or oral etoposide), targeted therapies, immunotherapy or radiotherapy.
2) Prior treatment with hypomethylating agents and/or low dose cytarabine. Prior treatment with lenalidomide or similar agents was permitted if treatment was utilized for symptomatic support (ie, anemia, red blood cell [RBC] transfusion dependence).
3) Patients participated in an interventional clinical trial during study observation period.
4) Previous hematopoietic stem cell transplant (SCT) within 6 months prior to initiation of AZA, active graft versus host disease (GVHD), or requiring transplant-related immunosuppression.
5) Patients who have had transformation of MDS into acute myeloid leukemia (AML) prior to initiation of AZA.
6) Known inherited or acquired bleeding disorders.
7) EHR documentation of clinical suspicion/radiological evidence of active central nervous system (CNS) involvement by leukemia.
8) Acute promyelocytic leukemia.
9) Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients were not on active anticancer therapy as defined in Exclusion Criterion 1.
10) Initiation of AZA treatment outside the approved label (except as described under the Inclusion Criterion 5); for example, in combination with other agents for the treatment of MDS.

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Special population of interest

Other

Special population of interest, other

Patients with myelodysplastic syndrome

Estimated number of subjects

382
Study design details

Main study objective

The primary objective of this study was to evaluate the effectiveness of AZA monotherapy as assessed by CR rates defined by the IWG 2006 MDS criteria in patients with intermediate, high, and very high-risk MDS.

Outcomes

Complete remission rate, Real-world(rw) CR rate, objective response rate (ORR), rw-ORR, duration of CR (DCR), rw-DCR, duration of response (DOR), rw-DOR, Progression-Free Survival, time to next treatment, and overall survival.

Data analysis plan

Continuous variables were summarized by mean, standard deviation, median, 25% & 75% quantiles, minimum and maximum. Categorical variables were summarized by number and % of patients in each categorical definition including 95% confidence intervals. The Full Analysis Set (FAS) included all enrolled patients who took at least 1 dose of AZA. The Effectiveness Evaluable Analysis Set (EEAS) included all FAS patients who had at least 1 response assessment or died after the index date. The efficacy analyses (except DCR, rw-DCR, DOR, and rw-DOR) was performed on the FAS. DCR and rw-DCR were evaluated using FAS patients who achieved a CR and rw-CR, respectively. DOR and rw-DOR were evaluated using FAS patients who achieved an OR and real-world objective response (rw-OR), respectively. Details of analytical comparison with magrolimab and AZA combination therapy trial (5F9005) data were included in the statistical analysis plan.
Documents
Study results

GS-US-545-5956-Synopsis_f-redact

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