Incidence, Prevalence, and Real-World Treatment Patterns in Chronic Myeloid Leukemia: Results from a Population-Representative German Claims Data Analysis.

INTRODUCTION: Real-world data on usage of 1st-, 2nd-, and 3rd-generation tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML) are scarce. This study therefore aimed to analyze the use of different TKIs used in 1st- and 2nd-line treatment and the frequency of TKI switches in CML. METHODS: This observational study was based on the InGef research database, an anonymized representative claims dataset in Germany (n = 4 million). An incidence and prevalence patient CML cohort was followed for 5 and 3 years. Analyses regarding incidence, prevalence, and therapy distribution were performed descriptively. RESULTS: 151 patients were included in the incidence and 636 patients in the prevalence cohort. This resulted in an incidence of 1.8 (95% confidence interval [CI]: 1.34-2.20) and a prevalence of 14.9 (95% CI: 13.70-16.03) per 100,000 inhabitants. For the incidence cohort, data on 1st-line therapy were available for 124 patients and distributed across imatinib (N = 52), nilotinib (N = 44), dasatinib (N = 12), chemotherapies as hydroxycarbamide (N = 11), and ponatinib/bosutinib (N = 5). Twenty-six percent of patients switched TKI therapy at least once in 3 years. In the prevalence cohort, 423 patients (66.5%) had claims on existing or newly emerged cardiovascular diseases (CDs). No significant differences (p = 0.32) between TKIs in patients with CD were found. DISCUSSION: Every fourth patient switched TKI therapy within the first 3 years after treatment initiation. Switches were more likely when hints of disease progression or intolerability were observable in the database.

Correction: High-risk additional chromosomal abnormalities at low blast counts herald death by CML.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High-risk additional chromosomal abnormalities at low blast counts herald death by CML.

Blast crisis is one of the remaining challenges in chronic myeloid leukemia (CML). Whether additional chromosomal abnormalities (ACAs) enable an earlier recognition of imminent blastic proliferation and a timelier change of treatment is unknown. One thousand five hundred and ten imatinib-treated patients with Philadelphia-chromosome-positive (Ph+) CML randomized in CML-study IV were analyzed for ACA/Ph+ and blast increase. By impact on survival, ACAs were grouped into high risk (+8, +Ph, i(17q), +17, +19, +21, 3q26.2, 11q23, -7/7q abnormalities; complex) and low risk (all other). The presence of high- and low-risk ACAs was linked to six cohorts with different blast levels (1%, 5%, 10%, 15%, 20%, and 30%) in a Cox model. One hundred and twenty-three patients displayed ACA/Ph+ (8.1%), 91 were high risk. At low blast levels (1-15%), high-risk ACA showed an increased hazard to die compared to no ACA (ratios: 3.65 in blood; 6.12 in marrow) in contrast to low-risk ACA. No effect was observed at blast levels of 20-30%. Sixty-three patients with high-risk ACA (69%) died (n = 37) or were alive after progression or progression-related transplantation (n = 26). High-risk ACA at low blast counts identify end-phase CML earlier than current diagnostic systems. Mortality was lower with earlier treatment. Cytogenetic monitoring is indicated when signs of progression surface or response to therapy is unsatisfactory.

Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV.

Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12-15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.