Real-World Treatment Patterns and Outcomes Among Patients With Chronic Myeloid Leukemia in Earlier Lines of Therapy (ABL-2022-03)

Real-World Treatment Patterns and Outcomes Among Patients With Chronic Myeloid Leukemia in Earlier Lines of Therapy (ABL-2022-03)

This was a retrospective, non-interventional, observational cohort study using Optum's de-identified Clinformatics® Data Mart Database. Adult patients newly diagnosed with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) were identified using the Optum database and classified into the following cohorts:

• First treatment cohort: Patients newly diagnosed with CML who received first treatment with a TKI.
• Second treatment cohort: Patients from first treatment cohort with a subsequent line of therapy (i.e., second treatment) with a TKI.

The observation period spanned from the start of data availability (i.e., 01 January 2007) to the earliest of end of data (i.e., 30 June 2022), end of continuous health plan enrollment, or death (if available). The index date was defined as the first treatment initiation for the first treatment TKI cohort and as the second treatment initiation for the second treatment TKI cohort. The baseline period consisted of the 6 months prior to the index date. The follow-up period started on the index date and ended at the earliest of end of observation period or hematopoietic stem cell transplantation (HSCT).

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukemia

• Study Type: Observational
• Enrollment (Actual): 2043

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, noninterventional cohort study.

Description

Inclusion Criteria:

• Adult patients who initiated their first treatment with imatinib, dasatinib, nilotinib, or bosutinib (conditional on Food and Drug Administration (FDA) approval dates) with 6 months continuous health plan enrollment prior to the first prescription fill date.
• Patients with 2 or more diagnoses for CML (adult as of the first diagnosis for CML).
• Patients had index date on or after first CML diagnosis.
• Patients had no diagnoses for CML remission/relapse prior to index date.
• Patients had no gastrointestinal stomach tumor (GIST) or chronic myelomonocytic leukemia (CMML) at any time.
• Patients had no medical claims associated with a clinical trial during the baseline period.
• Patients had no hematopoietic stem cell transplantation (HSCT) during the baseline period.
• Patients had no CML-related chemotherapy treatments for accelerated phase (AP)/blast crisis (BC) during the baseline period.

• First treatment cohort:

  • Patients started first treatment for CML with imatinib, dasatinib, nilotinib, or bosutinib in 2012 or later.
  • Patients had no HSCT during the first treatment baseline period.
  • Patients had no CML-related chemotherapy treatment for AP/BC during the first treatment baseline period.

• Second treatment cohort:

  • Patients started second treatment for CML with imatinib, dasatinib, nilotinib, or bosutinib in 2012 or later.
  • Patients had no HSCT from the first treatment baseline period up to second treatment initiation.
  • Patients had no CML-related chemotherapy treatment for AP/BC from the first treatment baseline period up to second treatment initiation.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
First Treatment Cohort; Patients newly diagnosed with CML who received first treatment with imatinib, dasatinib, nilotinib, or bosutinib.
Second Treatment Cohort; Patients from first treatment cohort with a subsequent line of therapy (i.e., second treatment) with imatinib, dasatinib, nilotinib, bosutinib, or ponatinib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Patterns	Tyrosine kinase inhibitor (TKI) treatment management patterns in CML patients on first line or second line TKI were assessed.	Up to approximately 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Days Covered (PDC)	PDC was defined as the number of days of medication covered divided by the number of calendar days during the study period. The study period spanned from index date to the next line of therapy initiation (switch), hematopoietic stem cell transplantation (HSCT), initiation of a CML-related chemotherapy for accelerated phase (AP)/blast crisis (BC) (day prior to HSCT/CML chemotherapy) or last supply day if treatment gap ≥ 90 days, whichever occurred first. The index date was defined as the first treatment initiation for the first treatment cohort and as the second treatment initiation for the second treatment cohort.	Up to approximately 10 years
Number of Patients per PDC Category	PDC was defined as the number of days of medication covered divided by the number of calendar days during the study period. The study period spanned from index date to the next line of therapy initiation (switch), HSCT, initiation of a CML-related chemotherapy for AP/BC (day prior to HSCT/CML chemotherapy) or last supply day if treatment gap ≥ 90 days, whichever occurred first. The index date was defined as the first treatment initiation for the first treatment cohort and as the second treatment initiation for the second treatment cohort. PDC categories included: PDC (%) ≤ 50%; PDC (%) ≤ 70%; PDC (%) ≥ 80%; PDC (%) > 90%	Up to approximately 10 years
Time to Treatment Discontinuation		Up to approximately 10 years
Time to Treatment Switch		Up to approximately 10 years
Time to First Treatment Interruption		Up to approximately 10 years
Time to First Dose Reduction		Up to approximately 10 years
Rate of Treatment Discontinuation		Months 1, 3, 6, 9, 12, 18, and years 2, 3, 4
Rate of Treatment Switching		Months 1, 3, 6, 9, 12, 18, and years 2, 3, 4
Rate of Treatment Interruption		Months 1, 3, 6, 9, 12, 18, and years 2, 3, 4
Rate of Dose Reduction		Months 1, 3, 6, 9, 12, 18, and years 2, 3, 4
Number of Patients With Non-optimal Treatment (NOPT)	Three categories of NOPT were defined: Base Case: NOPT was defined as 1) treatment switch ≤ 6 months post-index, 2) temporary treatment interruption/dose reduction ≤6 months post-index followed by treatment switch ≤12 months post-index, or 3) PDC ≤50%.; Sensitivity 1: NOPT was defined as 1) treatment switch ≤ 6 months post-index, 2) temporary treatment interruption/dose reduction ≤6 months post-index followed by treatment switch ≤12 months post-index, or 3) PDC ≤70%.; Sensitivity 2: NOPT was defined as treatment switch ≤ 6 months post-index. Index date was defined as the first treatment initiation for the first treatment cohort and as the second treatment initiation for the second treatment cohort.	Up to approximately 10 years
Number of Patients With NOPT by First Generation TKI	Three categories of NOPT were defined: Base Case: NOPT was defined as 1) treatment switch ≤ 6 months post-index, 2) temporary treatment interruption/dose reduction ≤6 months post-index followed by treatment switch ≤12 months post-index, or 3) PDC ≤50%.; Sensitivity 1: NOPT was defined as 1) treatment switch ≤ 6 months post-index, 2) temporary treatment interruption/dose reduction ≤6 months post-index followed by treatment switch ≤12 months post-index, or 3) PDC ≤70%.; Sensitivity 2: NOPT was defined as treatment switch ≤ 6 months post-index. Index date was defined as the first treatment initiation for the first treatment cohort and as the second treatment initiation for the second treatment cohort.	Up to approximately 10 years
Number of Patients With NOPT by Second Generation TKI	Three categories of NOPT were defined: Base Case: NOPT was defined as 1) treatment switch ≤ 6 months post-index, 2) temporary treatment interruption/dose reduction ≤6 months post-index followed by treatment switch ≤12 months post-index, or 3) PDC ≤50%.; Sensitivity 1: NOPT was defined as 1) treatment switch ≤ 6 months post-index, 2) temporary treatment interruption/dose reduction ≤6 months post-index followed by treatment switch ≤12 months post-index, or 3) PDC ≤70%.; Sensitivity 2: NOPT was defined as treatment switch ≤ 6 months post-index. Index date was defined as the first treatment initiation for the first treatment cohort and as the second treatment initiation for the second treatment cohort.	Up to approximately 10 years
All-cause Healthcare Resource Utilization (HRU) per Patient per Year in NOPT Patients Compared to Reference Subgroup	The reference subgroup was defined based on the following treatment adherence and persistence criteria denoting potential indicators of TKI treatment success based on observations from the clinical practice: (1) high treatment adherence (defined as PDC >90%) with no observed treatment discontinuation anytime post-index; or (2) high treatment adherence (defined as PDC >90%) with treatment discontinuation occurring >12 months post-index. All-cause HRU included: Inpatient admission; Inpatient days; Emergency department visits; Outpatient visits	2 years
CML-related HRU per Patient per Year in NOPT Patients Compared to Reference Subgroup	The reference subgroup was defined based on the following treatment adherence and persistence criteria denoting potential indicators of TKI treatment success based on observations from the clinical practice: (1) high treatment adherence (defined as PDC >90%) with no observed treatment discontinuation anytime post-index; or (2) high treatment adherence (defined as PDC >90%) with treatment discontinuation occurring >12 months post-index. All-cause HRU included: Inpatient admission; Inpatient days; Emergency department visits; Outpatient visits	2 years
All-cause Direct Healthcare Costs per Patient per Year in NOPT Patients Compared to Reference Subgroup	The reference subgroup was defined based on the following treatment adherence and persistence criteria denoting potential indicators of TKI treatment success based on observations from the clinical practice: (1) high treatment adherence (defined as PDC >90%) with no observed treatment discontinuation anytime post-index; or (2) high treatment adherence (defined as PDC >90%) with treatment discontinuation occurring >12 months post-index. All-cause direct healthcare costs included: Total medical costs; Inpatient costs; Outpatient costs; Emergency department costs	2 years
CML-related Direct Healthcare Costs per Patient per Year in NOPT Patients Compared to Reference Subgroup	The reference subgroup was defined based on the following treatment adherence and persistence criteria denoting potential indicators of TKI treatment success based on observations from the clinical practice: (1) high treatment adherence (defined as PDC >90%) with no observed treatment discontinuation anytime post-index; or (2) high treatment adherence (defined as PDC >90%) with treatment discontinuation occurring >12 months post-index. All-cause direct healthcare costs included: Total medical costs; Inpatient costs; Outpatient costs; Emergency department costs	2 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Estimated): November 18, 2024

Study Record Updates

• Last Update Posted (Estimated): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: CABL001A0US04