scholarly journals Evaluating Real-World Effectiveness and Safety of Generic and Brand-Name Imatinib in Chronic Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3614-3614
Author(s):  
Michele Muir ◽  
Jasmine Johnson ◽  
Sitong Shu ◽  
Hui-Han Chen ◽  
Sachiko Ozawa ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Primary Endpoint ◽  
Real World ◽  
Myeloid Leukemia ◽  
Statistical Significance ◽  
The United States ◽  
Emergency Department Visits ◽  
Imatinib Treatment ◽  
First Line ◽  
Branded Product

Abstract Introduction: Generic formulations of imatinib were approved and commercially available in the United States starting in 2016, introducing vast cost savings to the standard treatment of chronic myeloid leukemia (CML). While bioequivalence studies of generic formulations are required for Food and Drug Administration approval, the safety of generic drug supply chains have come into question. There is limited real-world data comparing the effectiveness and safety profiles of generic formulations to the original. This study aimed to evaluate the effectiveness and safety of generic imatinib compared to the branded product. Methods: This retrospective study included patients treated at UNC Medical Centers who were diagnosed with CML and treated with imatinib at any time during their course of treatment. Data was retrieved from the institution's electronic health record and collected over the first 6 months of imatinib treatment to include both safety and effectiveness outcomes. The primary endpoint was to compare generic versus branded product effectiveness, as defined by the European LeukemiaNet (ELN) guidelines (achieving BCR-ABL/ABL ratio of <10% and <1% at 3 and 6 months, respectively). The secondary endpoints included comparisons of generic vs branded product safety, measured via patient adverse drug events (ADEs), all-cause hospitalizations, and early treatment discontinuation. Patients were excluded from primary endpoint evaluation and only included for safety endpoint analysis if they were not treated with imatinib first-line and if duration of imatinib treatment was less than 6 months. Results: Fifty-one CML patients met criteria with no significant differences in age or gender between the generic (n = 23) and brand (n = 28) imatinib groups (Table 1). First-line therapy was composed of 83% of patients on generic imatinib and 29% of patients on brand imatinib. Of those receiving first-line imatinib therapy, there was no difference in molecular responses at 3 and 6 months between generic and brand imatinib (p = 0.71). Brand imatinib was associated with numerically lower CML-related emergency department visits and hospitalizations when compared to generic imatinib, although this difference was not statistically significant (p = 0.12). Rates of discontinuation were numerically lower for brand imatinib although overall time to discontinuation was shorter for generic imatinib (Table 1). Conclusions: This study demonstrates real-world treatment effectiveness and safety of generic and brand imatinib in clinical practice. Generic imatinib appears to be associated with higher rates of CML-related ED visits and hospitalizations although sample size was small and statistical significance was not reached. Further analyses of comparisons and continuation of data collection will provide a more robust assessment to compare the effectiveness and safety of generic and brand imatinib in the real-world setting. Figure 1 Figure 1. Disclosures Muluneh: Novartis: Other: Spouse works for Novartis.

scholarly journals BCR-ABL1 genomic DNA PCR response kinetics during first-line imatinib treatment of chronic myeloid leukemia

Haematologica ◽  
2018 ◽  
Vol 103 (12) ◽  
pp. 2026-2032 ◽  
Author(s):  
Ilaria S. Pagani ◽  
Phuong Dang ◽  
Ivar O. Kommers ◽  
Jarrad M. Goyne ◽  
Mario Nicola ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Genomic Dna ◽  
Myeloid Leukemia ◽  
Imatinib Treatment ◽  
First Line ◽  
Dna Pcr

Real-world prescribing patterns in acute myeloid leukemia in the United States.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18524-e18524 ◽  
Author(s):  
Bruno C. Medeiros ◽  
Bhavik J. Pandya ◽  
Anna Hadfield ◽  
Samuel Wilson ◽  
Cynthia Mueller ◽  
...  
Keyword(s):  
United States ◽  
Acute Myeloid Leukemia ◽  
Real World ◽  
High Intensity ◽  
Myeloid Leukemia ◽  
Patient Characteristics ◽  
The United States ◽  
First Line ◽  
Low Intensity ◽  
Acute Myeloid

e18524 Background: The effective treatment of patients with acute myeloid leukemia (AML) remains a challenge in clinical practice. This analysis describes the patient characteristics and real-world use of AML treatments in the United States for patients on high- and low-intensity treatment. Methods: Data from the Adelphi AML Disease-Specific Programme, a real-world, cross-sectional survey conducted between February–May 2015, were analysed. A total of 61 hematologist/hem-oncologists, across academic, non-academic and office-based practice locations, provided data on 457 AML patients. Patient characteristics were derived from physician-completed patient record forms where each physician was asked to provide treatment details, including the treatment intensity, for each line of therapy. Results: A total of 91% (n = 415) of patients included in this analysis were previously untreated for AML. Patients had a mean age of 60 years and been diagnosed with AML for a median of 5.0 months. At first-line induction therapy, over half (53%; n = 241) of the patients were initiated on a high-intensity treatment, the most common regimen being cytarabine plus anthracycline (61%; n = 147). The remaining 47% (n = 216) of patients received a low-intensity induction therapy such as low dose cytarabine monotherapy (28%, n = 61), azacitidine monotherapy (25%, n = 54), or decitabine monotherapy (21%, n = 45). Over half (55%, n = 62) of patients suited to high intensity treatment went on to receive cytarabine monotherapy during the consolidation phase of their first-line treatment. Conclusions: According to treating physicians, the large majority of patients receive traditional, well-established therapies at first-line induction for AML. Whilst cytarabine combinations dominate the high-intensity treatment setting, the hypomethylating agents, azacitidine and decitabine, are frequently used for those more suited to low-intensity treatment.

Evaluation Of hOCT1expression In Patients With Chronic Myeloid Leukemia (CML) Treated With Imatinib In First Line

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4041-4041
Author(s):  
Cintia Do Couto Mascarenhas ◽  
Maria Helena Almeida ◽  
Eliana C M Miranda ◽  
Bruna Virgilio ◽  
Marcia Torresan Delamain ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Taqman Probe ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
First Line ◽  
Transcript Levels

Abstract Introduction The majority of chronic myeloid leukemia (CML) patients (pts) in chronic phase (CP), present satisfactory response to imatinib treatment. However, 25-30% of these pts exhibit suboptimal response or treatment failure. The probability of achieving optimal response may be related with several factors. The human organic cation transporter 1 (hOCT1, SLC22A1), an influx transporter, is responsible for the uptake of imatinib into chronic myeloid leukemia (CML) cells The aim of this study was to analyze hOCT-1 levels at diagnosis of CML patients and correlate with cytogenetics and molecular responses. Methods hOCT-1 expression was evaluated in 58 newly diagnosed CML pts. Pts were treated with imatinib 400-600mg in first line. Samples were collected from peripheral blood at diagnosis and RNA was obtained from total leucocytes. For cDNA synthesis, 3 ug of RNA was used. hOCT-1 expression was evaluated by real-time PCR with TaqMan probe SLC22A1 (Applied Biosystems) and endogenous GAPDH control. The results were analyzed using 2-ΔΔCT. Cytogenetic analysis was performed at diagnosis, 3, 6, 12 and 18 months after starting therapy and then every 12-24 months thereafter if CCR was achieved. BCR-ABL transcripts were measured in peripheral blood at 3-month intervals using quantitative RT-PCR (RQ-PCR). Results were expressed as BCR-ABL/ABL ratio, with conversion to the international scale (IS). Major molecular response (MMR) was defined as a transcript level ≤ 0.1%. Results 58 CML pts, 60% male, median age of 46 years (19-87) were evaluated, 71% in chronic phase (CP), 21% in accelerated phase (AP) and 5% in blast crisis (BC). The mean and median of hOCT-1 transcript levels in the total group was 2.03 and 0.961 respectively (0.008–19.039) and CP pts was 1.86 and 1.00 (0.008-10.34).The median duration of imatinib treatment was 27 months (1-109) and 96.6% achieved complete hematological response, 79.3% complete cytogenetic response and 69% major or complete molecular response. The regression analysis showed correlation between higher transcript levels of hOCT-1 and BCR-ABL transcripts<10%) at 3 months analysis (p<0.0001). Albeit, there was no influence of the hOCT-1 transcript levels at diagnosis in the achievement of cytogenetic and molecular response at 24 months of treatment. Conclusions In this report, we found that high hOCT-1 expression was predictive of BCR-ABL transcripts<10% at 3 months, although we did not find correlation between hOCT-1 levels at diagnosis and the achievement of molecular response at 24 months, studies show that there is correlation between BCR-ABL log reduction in the first months of treatment and the achievement of molecular response. Disclosures: No relevant conflicts of interest to declare.

SNPs in the Promoter of the Gene Encoding Transmembrane Transporter SLC22A4 (hOCTN1) Are Significantly Associated with an Alteration of Gene Expression and with Resistance to the Imatinib Treatment in Chronic Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2463-2463
Author(s):  
Monika Jaruskova ◽  
Rajna Hercog ◽  
Nikola Curik ◽  
Vladimir Benes ◽  
Hana Klamova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Kinase Domain ◽  
Imatinib Treatment ◽  
First Line ◽  
Promoter Regions ◽  
Optimal Response

Abstract Introduction: Apart from the mutations in the kinase domain of BCR-ABL, other important mechanisms of resistance to the first line imatinib (IM) therapy in chronic myeloid leukemia (CML) are pharmacokinetics factors, especially an intracellular concentration of IM. ATP Binding Cassette (ABC, ensuring efflux) and Solute Carrier (SLC, ensuring uptake) super families are responsible for transportation several drugs including IM. Gene expression and activity of the SLC and ABC transporters may be affected by polymorphisms in their promoter regions and may notably contribute to the treatment failure. Objectives: The aim of this study was to identify polymorphisms in the promoter regions of the selected SLC and ABC transporter encoding genes and evaluate their association with the response to the first line IM therapy in CML patients in chronic phase. Material and Methods: The patient cohort consists of 40 CML patients with optimal response and 40 resistant patients (without mutations in the BCR-ABL kinase domain) to the IM in the first line with 24 months follow-up from the therapy initiation. All 80 CML patients were taking a standard dose of IM and in none of them were evidence of non-compliance. The promoter regions (~1000bp) of selected ABC (n=4) and SLC (n=15) genes with the annotated function of drug transportation were amplified. The next generation sequencing was applied for ultra-wide sequencing of altogether 1419 amplicons (454 GS Junior, Roche AppliedScience; MiSeq Series, Illumina). The obtained sequences were analyzed and evaluated with the focus on the presence of single nucleotide polymorphisms (SNPs) using NextGENe software (Softgenetics). The Fisher´s exact binomial test of goodness of fit was used to evaluate haplotype frequency distribution among patient cohort. The expression analysis of a selected gene was analyzed using RT-qPCR (TaqMan® Assays) in total leukocytes of peripheral blood with GUS as a housekeeping gene. Results: Among 1419 evaluated sequences we identified 96 SNPs (2-12 SNPs per one promoter) of which nine was not yet annotated. We identified 2 SNPs, rs460089 (C/G) and rs460271 (C/G), with uniform alleles co-segregations in the promoter of the gene SLC22A4 when GG haplotypes were significantly more frequent in resistant patients (P<.05). Of all resistant patients, 69% carried GG haplotypes, 17% CG and 14% CC. The frequency of haplotypes among responding patients was 31% of GG, 53% CG and 16% CC. As SLC22A4 is imatinib transporter (He L et al. Hum Genomics 2009), we measured the level of the gene expression associated with both co-segregated SNPs. Among all patients analyzed regardless of the response to IM, the GG haplotypes showed a significantly lower expression of SLC22A4 in comparison to CG and CC haplotypes (P<.05). Even greater significant differences in the expression were found when comparing GG haplotypes within patients resistant to IM in comparison to CG haplotypes within patients with optimal response (P<.01). Conclusion: In this work, we found a significantly decreased gene expression of SLC22A4 in total leukocytes of peripheral blood that was associated with GG haplotypes of 2 SNPs in the SLC22A4 promoter, where GG haplotypes were significantly more frequent in CML patients resistant to the first line imatinib treatment in comparison to the patients with an optimal response. We assume that GG haplotypes have altered activity of SLC22A4 promoter resulting in the reduced hOCTN1 expression and thus in lower intracellular IM concentration that may be insufficient for optimal response. The experiments on the SLC22A4 promoter activity alterations associated with GG haplotypes are ongoing. We believe that screening for rs460089 (C/G) and rs460271 (C/G) SNPs among patients with newly diagnosed CML could be an important prognostic genetic factor helping to select a tyrosine kinase inhibitor that is not dependent on the active transportation through the cell membrane. This work was supported by the Ministry of Health of Czech Republic, grant IGA MZ CR NT/13899 and Charles University in Prague, project GA UK/177815. Disclosures Klamova: Bristol Myers-Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Machova Polakova:Bristol Myers-Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

scholarly journals Efficacy and Safety of Generic Dasatinib As First-Line Treatment in Patients with Chronic Myeloid Leukemia in Chronic Phase: Final Analysis with 2-Year Follow-up

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3616-3616
Author(s):  
Jie Jin ◽  
Li Meng ◽  
Wenjuan Yu ◽  
Peng Liu ◽  
Xin Du ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Primary Endpoint ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

Abstract Purpose: Generic dasatinib, a second-generation tyrosine kinase inhibitor (TKI), was approved as a second-line treatment for chronic myeloid leukemia (CML) patients in chronic phase (CP) in china. We initiated a prospective, multi-center and single-arm clinical trial (NCT04925141) from May 2016 to October 2018 to evaluate efficacy and safety of generic dasatinib as first-line treatment in China. The primary endpoint was achieved, here we reported the 2 years follow-up results to see its long-term clinical benefit in Chinese patients. Methods:The study included the newly diagnosed CML-CP patients who was diagnosed by the presence of Philadelphia (Ph) chromosome and/or presence of BCR-ABL fusion gene. Key inclusion criteria were as follows: 1) Age ≥ 18 years; 2) The CML subjects in chronic phase with the Ph+ definitive diagnosis were within 6 months before the onset of administration of the study drug; 3) The ECOG performance grades of 0-2; 4) Sufficient main organ functions. All newly diagnosed patients were given 100mg/d (initial dose) of the generic dasatinib. The primary endpoint was molecular major response (MMR) calculated based on the BCR-ABL1 ≤ 0.1% at the 12th month. Secondary endpoints were proportion of subjects who achieved and maintained MMR at 3, 6, and 18 months; Cumulative MMR rates at 6, 12, and 24 months were determined. All patients were followed up through the hospital outpatient departments at second, fourth and eighth weeks, and third, sixth, ninth, twelfth, eighteenth, and twenty-fourth months. The follow-up ended on December 6, 2019. The SAS 9.2 software was utilized for all statistical analyses in this study, and the two-sided test was performed to see variances. Results: A total of 59 patients were included in this trail, with median age of 44 (19 - 70), and 7% of the subjects were at high risk based on the Sokal index for the disease prognosis. The primary endpoint MMR rate at the 12th month was 80.8% which had been published. At 12 months, the cumulative response rate (CCyR) was 85.5% (47/55) and the cumulative MMR was 76.4% (42/55). Here we are reporting the 2 years follow ups. At 24 months, the complete hematological response (CHR) was 88.4%, the cumulative MMR rate was 73.7%, the cumulative MR4.0 rate was 63.6%, the cumulative MR4.5 rate was 58.2%, and the cumulative complete molecular response (CMR) rate was 58.2%. The most common adverse events (AEs) was thrombocytopenia (42.4%) in hematology and pleural effusion (20.3%) in non-hematology, only 11.9% and 1.7% of whom were grade III~IV respectively. Conclusion: This was the first report on domestic dasatinib as the first-line treatment for CML-CP patients received a clinical benefit with 24 months in China. Safety was similar with that of the original study data. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Adherence to Chronic Myeloid Leukemia Monitoring and Treatment Guidelines in Canadian Registries

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3079-3079
Author(s):  
Christopher M Hillis ◽  
Lambert Busque ◽  
Julie Stakiw ◽  
Donna L. Forrest
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Data Collection ◽  
Real World ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Treatment Guidelines ◽  
Imatinib Therapy ◽  
Molecular Monitoring ◽  
First Line ◽  
Time Period

Abstract Background: Registry data in chronic myeloid leukemia (CML) complement clinical trial data, and can help determine how closely real world clinical practice adheres to guidelines. Several reports addressing this issue have suggested adherence to monitoring guidelines varies. However, no Canadian data on this topic has been published to date. To provide insight into this issue, we present data from the British Columbia (BC), Saskatchewan (SK), Ontario (ON) and Quebec (QC) CML registries. Methods: Data on cytogenetic and molecular monitoring were analyzed for CML patients treated with first-line imatinib from 2001-2015 in the BC registry, 2009-2014 in the SK registry and 2001-2014 in the ON registry. From 2006, clinicians in BC and SK were advised to follow the European LeukemiaNet (ELN) monitoring recommendations. Molecular monitoring of BCR-ABL for these provinces was conducted at the BC Cancer Agency Molecular Genetics Laboratory according to standard practices. In ON, clinicians were not advised to follow any particular guidelines and molecular and cytogenetic tests were conducted by the Hamilton Regional Laboratory Medicine Program using contemporary standards. In QC, province-specific guidelines were in place beginning in 2012 (see www.gqr-lmc-nmp.ca for specific guidance). Treatment patterns for patients treated with first-line imatinib from BC, SK and QC were analyzed for the 2001-2015, 2001-2014 and 2002-2012 time periods, respectively. Results: Monitoring data were collected for 234, 58 and 104 patients from BC, SK and ON, respectively. As shown in table 1, adherence to monitoring recommendations in Canada was 70% to 80% at 12 months. Treatment data were available for 234 BC patients, 73 SK patients, and 223 QC patients. Data on adherence to treatment recommendations were available for 58 SK patients diagnosed with CML and treated with first-line imatinib between 2009 and 2014. Of these 58 patients, over a quarter (n=15) experienced treatment failure or failed to meet ELN milestones without a change in therapy. Smaller proportions of patients receiving first-line imatinib therapy in BC and QC remained on imatinib therapy (see table 2). Discussion and Conclusions: These data suggest there is room for improvement with regards to adherence to CML monitoring and treatment recommendations in Canada. However, assessment of adherence to recommendations and inter-provincial comparisons are limited by the fact that monitoring and treatment guidelines have evolved over the data collection time period, as well as by differences in data collection strategies. For instance, in the ON registry, monitoring at the 3-month time point may be lower as testing was not typically conducted at 3 months in ON during the early 2000s. The opposite pattern observed in BC (with higher testing rates at 3 months dropping off by 18 months) may be attributable to the strict time period definition, with more patients receiving testing outside of the 4-week window after 1 year or more on treatment. In spite of these limitations, data collection through these registries continues to improve our understanding of real world CML populations and its management in Canada, as well as to spur initiatives aimed at improving CML care. This study was sponsored by Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by MedPlan Communications Inc. and was funded by Bristol-Myers Squibb. Disclosures Hillis: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria; Celgene: Consultancy. Busque:Novartis: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Stakiw:Roche: Research Funding; BMS: Honoraria; Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Jansen: Honoraria, Speakers Bureau. Forrest:BMS: Consultancy, Research Funding; Ariad: Honoraria, Speakers Bureau.

Real-world response monitoring and tolerability of imatinib-treated chronic myeloid leukemia patients captured in a retrospective research registry.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6583-6583
Author(s):  
David D. Stenehjem ◽  
Frederick S. Albright ◽  
Min Amy Guo ◽  
Lei Chen ◽  
Karina Raimundo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Real World ◽  
Myeloid Leukemia ◽  
Response Monitoring ◽  
Molecular Testing ◽  
Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Impact

6583 Background: Monitoring tolerability and response to imatinib (IM) is an important aspect of chronic myeloid leukemia (CML) management. The objective of this study is to assess real-world tolerability and response monitoring in IM treated CML patients (pts). Methods: A comprehensive retrospective outcomes research registry of CML pts was created from the University of Utah electronic health record system. Study inclusion was limited to pts diagnosed with CML in chronic phase in 2001 to 2010 and treated with IM as a first-line therapy. Utilization and outcome of cytogenetic and molecular testing within 18 months of IM initiation, rates of adverse drug events (ADEs), and therapy modifications were evaluated by chart review. Results: A total of 92 pts were treated with IM as first-line therapy. Within the first 18 months of treatment, cytogenetic testing was recorded in 45 pts (49%) and of these 33 pts (73%) achieved a complete cytogenetic response (CCyR) in a median of 241 days (range: 110-542); molecular testing was completed in 48 pts (52%) and of these 24 pts (50%) achieved at least a major molecular response (MMR) in a median of 254 days (range: 99-546). Imatinib associated ADEs of any grade (n = 60) occurred in 42 (46%) pts resulting in dose reductions in 15 pts (36%) in a median of 77 days and discontinuation of IM occurred in 9 (21%) pts in a median of 130 days. The IM dose was increased to >400 mg in 21 (23%) pts in a median of 457 days (range: 21-2112). Of pts diagnosed between 2006 to 2010 (n = 34; 37%), 8 (25%) pts transitioned to dasatinib or nilotinib in a median of 397 days (range: 147 to 1057). Reasons for therapy change included physician documented suboptimal response or treatment failure (n = 5) and ADEs to IM (n = 3). Conclusions: Utilization of cytogenetic and molecular testing within 18 months of IM initiation was lower than the National Comprehensive Cancer Network or European LeukemiaNet CML guidelines would suggest. Further research is warranted to understand limited response monitoring and outcomes in non-monitored pts. The ADE rate was similar to clinical trial data. The impact of ADEs on subsequent treatment and outcomes in CML pts deserves further study.

Comparative Safety and Health Care Expenditures Among Patients With Chronic Myeloid Leukemia Initiating First-Line Imatinib, Dasatinib, or Nilotinib

2020 ◽  
Vol 16 (5) ◽  
pp. e443-e455 ◽  
Author(s):  
Ashley L. Cole ◽  
William A. Wood ◽  
Benyam Muluneh ◽  
Jennifer L. Lund ◽  
Jennifer Elston Lafata ◽  
...  
Keyword(s):  
Health Care ◽  
Emergency Department ◽  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Health Care Expenditures ◽  
Emergency Department Visits ◽  
First Line ◽  
Safety And Health ◽  
Comparative Safety

PURPOSE: Tyrosine kinase inhibitors (TKIs) have dramatically improved survival for patients with chronic myeloid leukemia (CML). No overall survival differences were observed between patients initiating first- and second-generation TKIs in trials; however, real-world safety and cost outcomes are unclear. We evaluated comparative safety and health care expenditures between first-line imatinib, dasatinib, and nilotinib among patients with CML. PATIENTS AND METHODS: Eligible patients had one or more fills for imatinib, dasatinib, or nilotinib in the MarketScan Commercial and Medicare Supplemental databases between January 1, 2011, and December 31, 2016 (earliest fill is the index date), 6 months pre-index continuous enrollment, CML diagnosis, and no TKI use in the pre-index period. Hospitalizations or emergency department visits (safety events) were compared across treatment groups using propensity-score-weighted 1-year relative risks (RRs) and subdistribution hazard ratios (HRs). Inflation-adjusted annual health care expenditures were compared using quantile regression. RESULTS: Eligible patients included 1,417 receiving imatinib, 1,067 receiving dasatinib, and 647 receiving nilotinib. The 1-year risk of safety events was high: imatinib, 37%; dasatinib, 44%; and nilotinib, 40%, with higher risks among patients receiving dasatinib (RR, 1.17; 95% CI, 1.06 to 1.30) and nilotinib (RR, 1.07; 95% CI, 0.93 to 1.23) compared with those receiving imatinib. Over a median of 1.7 years, the cumulative incidence of safety events was higher among patients receiving dasatinib (HR, 1.23; 95% CI, 1.10 to 1.38) and nilotinib (HR, 1.08; 95% CI, 0.95 to 1.24) than among those receiving imatinib. One-year health care expenditures were high (median, $125,987) and were significantly higher among patients initiating second-generation TKIs compared with those receiving imatinib (difference in medians: dasatinib v imatinib, $22,393; 95% CI, $17,068 to $27,718; nilotinib v imatinib, $19,463; 95% CI, $14,689 to $24,236). CONCLUSION: Patients receiving imatinib had the lowest risk of hospitalization or emergency department visits and 1-year health care expenditures. Given a lack of significant differences in overall survival, imatinib may represent the ideal first-line therapy for patients, on average.

Sign in / Sign up

Export Citation Format

Share Document