French Study to Highlight the Unmet Treatment Needs of 3L+ CP-CML and With T315I-mutated CML Patients

Study Overview
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Brief Summary
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A retrospective multi-center cohort study design was used to address the study objectives, using medical records obtained from three clinical centers in France.

Detailed Description
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The index date for patients in the 3L cohort was defined as the date of initiation of 3L therapy. The index date for the T315I cohort was defined as the date of treatment initiation with TKI or allogeneic stem cell transplantation (allo-SCT) after identification of T315I mutation status. The baseline (i.e., pre-index) period was defined as the 6 months prior to the index date, and the post-index period was defined as the time from the index date to the date of last patient contact or patient death. Patients who were alive at the end of the follow-up period were censored at the date of last contact.

Official Title
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A Multi-Center Retrospective Chart Review Study Examining the Patient Characteristics, Treatment Patterns, Clinical Outcomes, and Burden of Illness Among Patients With Chronic Myeloid Leukemia in Third-line Treatment or With T315I Mutation in France (CML 3L+ & T315I)

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Other: 3L Therapy
* Other: T315I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with CML-CP Age ≥18 years at the time of CML-CP diagnosis For 3L patients: initiated one of the following 3L therapies in CML-CP after failing on ≥2 TKIs (i.e., bosutinib, dasatinib, imatinib, nilotinib, or ponatinib) or allo-SCT For T315I mutation patients: evidence of T315I mutation and treatment with TKI or allo-SCT Exclusion Criteria: History of other active malignancies within the 3 years prior to the time of CML-CP diagnosis Documentation of anti-cancer therapies for any other malignancies prior to the time of 3L therapy initiation or at the time of treatment initiation after identification of T315I mutation Enrollment in a clinical trial at the time of 3L therapy initiation or at the time of treatment initiation after identification of T315I mutation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 3L+ Cohort<br>Patients who initiated third-line treatment (3L) therapy. Treatments received in 3L were dasatinib, nilotinib, imatinib, ponatinib, bosutinib, and allo-SCT | Other: 3L Therapy<br>* Treatments received in 3L were dasatinib, nilotinib, imatinib, ponatinib, bosutinib, and allo-SCT<br>* Other names: third-line treatment;|
| T315I cohort<br>Patients with chronic myeloid leukemia with T315I mutation | Other: T315I<br>* Patients with chronic myeloid leukemia with T315I mutation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients: Year patient initiated third-line treatment | Following categories included: Before 2010 2010-2014 2015-2019 2020-2021 | throughout the study (study used data from 2000 to 2021) | 
| Duration of third-line treatment | Duration of third-line treatment was reported | throughout the study (study used data from 2000 to 2021) | 
| Number of patients: Type of therapy received in third-line treatment | TKI agent Allo-SCT | throughout the study (study used data from 2000 to 2021) | 
| Time from 2L discontinuation to third-line treatment initiation | Time from 2L discontinuation to third-line treatment initiation was reported | throughout the study (study used data from 2000 to 2021) | 
| Number of patients still on 3L therapy as of data collection date | Number of patients still on 3L therapy as of data collection date was reported | throughout the study (study used data from 2000 to 2021) | 
| Number of patients discontinued 3L | Number of patients who discontinued 3L treatment were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of patients: Reasons for 3L discontinuation | Treatment switch due to AEs or intolerance Treatment switch due to resistance Treatment switch due to signs of ineffectiveness Treatment switch due to other reasons | throughout the study (study used data from 2000 to 2021) | 
| Number of lines of therapy for patients with chronic myeloid leukemia in third-line treatment | Number of lines of therapy for patients with chronic myeloid leukemia in third-line treatment were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of most frequent treatment sequences for patients with chronic myeloid leukemia in third-line treatment | Number of most frequent treatment sequences for patients with chronic myeloid leukemia in third-line treatment were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of last line of therapy for patients with chronic myeloid leukemia in third-line treatment | Number of last line of therapy for patients with chronic myeloid leukemia in third-line treatment were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of patients: Year patient initiated on the line identified as T315I line of interest | Following categories included: Before 2010 2010-2014 2015-2019 | throughout the study (study used data from 2000 to 2021) | 
| Duration of the line identified as T315I line of interest | Duration of the line identified as T315I line of interest was reported | throughout the study (study used data from 2000 to 2021) | 
| Number of patients: Type of therapy received in the line identified as T315I line of interest | TKI agent Allo-SCT | throughout the study (study used data from 2000 to 2021) | 
| Number of patients still on line of therapy identified as T315I line of interest as of data collection date | Number of patients still on line of therapy identified as T315I line of interest as of data collection date were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of patients: Reasons for discontinuation on the line identified as T315I line of interest | Adverse events or intolerance Resistance Signs of ineffectiveness Suboptimal response Progression to accelerated phase or blast phase Other reasons Acquired mutations | throughout the study (study used data from 2000 to 2021) | 
| Number of lines of therapy for patients with chronic myeloid leukemia with T315I mutation | Number of lines of therapy for patients with chronic myeloid leukemia with T315I mutation were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of line identified as T315I line of interest | Number of line identified as T315I line of interest were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of treatment sequence for patients with chronic myeloid leukemia with T315I mutation | Number of treatment sequence for patients with chronic myeloid leukemia with T315I mutation were reported | throughout the study (study used data from 2000 to 2021) | 
| Number of last line of therapy for patients with chronic myeloid leukemia with T315I mutation | Number of last line of therapy for patients with chronic myeloid leukemia with T315I mutation were reported | throughout the study (study used data from 2000 to 2021) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytogenetic response (CyR) for 3L patients | CCyR, defined as an absence of Philadelphia chromosome-positive (Ph+) metaphases in bone marrow cytogenetics | 12 and 24 months | 
| Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 12 months | Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 12 months were reported | 12 months post treatment | 
| Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 24 months | Proportion of patients achieving response among patients with chronic myeloid leukemia in third-line treatment in 24 months were reported. | 24 months post treatment | 
| Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 12 months | Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 12 months were reported. | 12 months post treatment | 
| Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 24 months | Proportion of patients achieving sustained molecular responses among patients with chronic myeloid leukemia in third-line treatment in 24 months were reported. | 24 months post treatment | 
| Time to major molecular response (MMR) among patients with chronic myeloid leukemia in third-line treatment | Time to MMR was defined as the time from third-line (3L) treatment initiation to the time patients achieved MMR (i.e., 0.01% IS < BCR::ABL1 transcript level ≤ 0.1% IS). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death. | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Time to deep molecular response (MR4.0) among patients with chronic myeloid leukemia in third-line treatment | Time to MR4.0 was defined as the time from third-line (3L) treatment initiation to the time patients achieved MR4.0 (i.e., 0.0032% IS < BCR::ABL1 transcript level ≤ 0.01% IS). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death. | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Time to sustained deep molecular response (MR4.0) among patients with chronic myeloid leukemia in third-line treatment | Time to sustained MR4.0 was defined as the time from third-line (3L) treatment initiation to the time patients achieved sustained MR4.0 or better (i.e., BCR::ABL1 ≤ 0.01%) in all consecutive assessments performed for at least 12 months (i.e., 365.25 days). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death. | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Time to deep molecular response (MR4.5) among patients with chronic myeloid leukemia in third-line treatment | Time to MR4.5 was defined as the time from third-line (3L) treatment initiation to the time patients achieved MR4.5 (i.e., 0.001% IS ≤ BCR::ABL1 transcript level ≤ 0.0032% IS). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death. | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Time to sustained deep molecular response (MR4.5) among patients with chronic myeloid leukemia in third-line treatment | Time to sustained MR4.5 was defined as the time from third-line (3L) treatment initiation to the time patients achieved sustained MR4.5 or better (i.e., BCR::ABL1 ≤ 0.0032%) in all consecutive assessments performed for at least 2 years (i.e., 730.5 days). Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, end of data availability, or death. | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Time to Progression-free survival (PFS) for 3L patients | Time to PFS was defined as the time from third-line treatment initiation to earliest occurrence of documented disease progression to accelerated phase or blast crisis, or the date of death from any cause. Patients were censored at the earliest of treatment discontinuation or switch, loss to follow-up, or end of data availability. | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Time to Overall Survival (OS) for 3L patients | Time to OS was defined as the time from third-line treatment initiation to death from any cause. Patients were censored at the earliest of treatment discontinuation or switch, date of last follow-up, or end of data availability. | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Time to treatment discontinuation (TTD) for 3L patients | TTD was defined as the time from third-line treatment initiation to treatment discontinuation or switch. Patients were censored at the earliest of loss to follow-up, or end of data availability, or death | 12, 24, 36, 48, 60, 72 and 84 months post treatment | 
| Proportion of patients with Adverse Events (AEs) in third-line treatment | Proportion of patients with Adverse Events (AEs) were reported to evaluate the safety profile of third-line treatments for chronic myeloid leukemia | throughout the study (study used data from 2000 to 2021) | 
| Age of patients with chronic myeloid leukemia in third-line treatment | Age information was reported. | Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021) | 
| Number of patients: Year of chronic myeloid leukemia in chronic phase (CML-CP) diagnosis of patients with chronic myeloid leukemia in third-line treatment | Year of CML-CP diagnosis of patients with chronic myeloid leukemia in third-line treatment was reported. | throughout the study (study used data from 2000 to 2021) | 
| Sex of patients with chronic myeloid leukemia in third-line treatment | Sex information was reported. | Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021) | 
| Number of patients: Medical center of patients with chronic myeloid leukemia in third-line treatment | The following centers were included: Centre Léon Bérard, Lyon Hématologie Institut Bergonié, Bordeaux Institut Universitaire du Cancer Toulouse, Toulouse | Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021) | 
| Length of follow-up (month) characteristics of patients with chronic myeloid leukemia in third-line treatment | Length of follow-up was defined as time from index date to the date of last known contact with patient or patient death. | throughout the study (study used data from 2000 to 2021) | 
| Number of patients: Smoking status at index date of patients with chronic myeloid leukemia in third-line treatment | Smoking status at index date of patients with chronic myeloid leukemia in third-line treatment was reported. | Index date defined as the date of initiation of 3L therapy (data from 2000 to 2021) | 
| Time from CML-CP diagnosis to index date (month) of patients with chronic myeloid leukemia in third-line treatment | Time from CML-CP diagnosis to index date (month) of patients with chronic myeloid leukemia in third-line treatment was reported. | throughout the study (study used data from 2000 to 2021) | 
| Number of patients with Hasford score at CML-CP diagnosis (month) of patients with chronic myeloid leukemia in third-line treatment | Low risk (≤780) Intermediate risk (>780 to ≤1480) High risk (>1480) Not assessed Unknown / not sure | throughout the study (study used data from 2000 to 2021) | 
| Number of patients with Sokal score at CML-CP diagnosis (month) of patients with chronic myeloid leukemia in third-line treatment | Low risk (<0.8) Intermediate risk (≥0.8 to ≤1.2) High risk (>1.2) Not assessed Unknown / not sure | throughout the study (data source from 2000 to 2021) | 
| Number of patients with ELTS risk score at CML-CP diagnosis (month) of patients with chronic myeloid leukemia in third-line treatment | ELTS: EUTOS long-term survival Low risk (≤1.5680) Intermediate risk (>1.5680 to ≤2.2185) High risk (>2.2185) Not assessed Unknown / not sure | throughout the study (data source from 2000 to 2021) | 
| Number of patients with BCR::ABL1 rearrangement at CML-CP diagnosis of patients with chronic myeloid leukemia in third-line treatment | Major Minor Other | throughout the study (data source from 2000 to 2021) | 
| Number of patients with Additional chromosomal abnormalities at CML-CP diagnosis of patients with chronic myeloid leukemia in third-line treatment | Yes No | throughout the study (study used data from 2000 to 2021) | 
| Number of comorbid conditions prior to the index date in patients with chronic myeloid leukemia in third-line treatment | Number of comorbid conditions prior to the index date in patients with chronic myeloid leukemia in third-line treatment were reported. | Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy) | 
| Number of patients with comorbid conditions prior to the index date in patients with chronic myeloid leukemia in third-line treatment | Cardiovascular disease Pulmonary disease/pulmonary arterial hypertension Gastrointestinal issues Renal disease Diabetes Liver disease Other No comorbidities Unknown / not sure | Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy) | 
| Number of patients with any ischemic condition prior to the index date in patients with chronic myeloid leukemia in third-line treatment | Cardiovascular disease Cerebrovascular disease Peripheral arterial | Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy) | 
| Number of patients with Cardiovascular risk factors prior to the index date in patients with chronic myeloid leukemia in third-line treatment | Hypertension Hyperlipidemia/dyslipidemia Diabetes Obesity | Baseline (6 months prior to index date, defined as the date of initiation of 3L therapy) | 
| Laboratory and clinical results: Random blood glucose (mg/dl) | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Laboratory and clinical results: Fasting blood glucose (mg/dl) | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Laboratory and clinical results: LDL cholesterol (mg/dl) | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Laboratory and clinical results: Total cholesterol (mg/dl) | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Laboratory and clinical results: Blood pressure | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Laboratory and clinical results: Spleen size below costal margin | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Laboratory and clinical results: Blood cell count | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Laboratory and clinical results: Bone marrow differential cell count | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Number of patients with BCR::ABL1 mutation status by line of therapy for patients with chronic myeloid leukemia in third-line treatment | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 
| Proportion of patients achieving response among patients with chronic myeloid leukemia with T315I mutation | Laboratory and clinical results were reported. | throughout the study (study used data from 2000 to 2021) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCR::ABL,, Chronic myeloid leukemia,, Tyrosine kinase inhibitor,, T315I mutation