Outcomes and Treatment Patterns of Patients with CML in an Inner-City, Underserved, Multi-Ethnic Patient Cohort Reveals Good Overall Survival with Both First and Second Generation TKIs As Initial Therapy
Authors: Assal Amer , Medavarapu Ramadevi , Friedman Ellen W , Yu Yiting , Verma Amit , Derman Olga 
Published: October 2019

Abstract
Introduction:
Recent approval of second generation tyrosine kinase inhibitors (TKI) in chronic myelogenous leukemia (CML) has raised issues about their efficacy and pharmaco-economic utility in front line therapy of CML. We aimed to study these issues as well as reasons for switching TKIs in a real world setting of inner-city, multi-ethnic, underserved patient populations.
Methods:
We conducted an analysis of CML treatment and outcomes in an inner city cohort in the Bronx, NY. We identified 149 confirmed cases of CML that were treated over the last 17 years. All chart review was conducted by one of the study authors and discrepancies were reviewed by at least two of the authors. Data were analyzed using Chi-squared, t-testing for unpaired samples, and analysis of variance (ANOVA) to determine significance. Mortality was analyzed using Kaplan-Meir curves.
Results:
Demographics and Presentation:The mean age at time of presentation was 50 years (range 10 - 89 years, n=124). Average follow-up time was 5.1 (± 3.9) years. The cohort was minority rich and included 38.9% Hispanic, 32.9% African American, 18.8% Caucasian, 6.7% Asian and 2.7% multi-ethnic. The majority of the patients had private insurance or Medicare (62.4%), followed by Medicaid (30.9%) and emergency Medicaid (6.7%). The majority of evaluable patients presented in chronic phase (96.1%).
Treatment Patterns: Front-line therapy was a 1st generation TKI (imatinib) in the majority of evaluable patients (83.9%) followed by a 2nd generation TKI (dasatinib or nilotinib) (11%). Rates of imatinib use as first line therapy were similar for both Private/Medicare (82.1%) and Medicare (88.1%) patients. Interestingly, a higher percentage of patients with Emergency Medicaid were started on a 2nd generation TKI (22.2%) as opposed to Private/Medicare and Medicaid (9.0% and 11.9% respectively). This was due to the availability of patient assistance programs to pay for TKIs. After the approval of dasatinib and nilotinib in 2008, there was increased use of the 2nd generation TKIs as first line though a majority of patients were still treated with imatinib as first line (72.2%, 80.0%, and 66.7% for Private/Medicare, Medicaid and Emergency Medicaid respectively).
Outcomes:At the time of conclusion of the study, a total of 31 patients had expired. Twenty patients were evaluable for therapy at the time of death, percentages of patients on 1st, 2nd and 3rd line therapy were 10%, 50%, and 25% respectively. Allogeneic stem cell transplant was performed in 15% of expired patients.
Of evaluable live patients (n=109), 45.9% were receiving the original front line therapy, whereas 37.6% and 16.5% were receiving second and third line therapies respectively. Regarding reasons for switch from a one TKI to another, we noted 34 patients who had been switched from a 1st to a 2nd generation TKI. Progression of disease was the cause in 53.0% of cases, followed by lack of response (17.6%), adverse events (14.7%), cytopenias (8.8%) and intolerance (5.9%). Two patients were switched from a 2nd generation TKI to a 1st generation, and both cases were due to intolerance.
Overall survival of the cohort at 2 and 5 years was 94% and 82% respectively. No differences in survival were detected between different ethnicities, gender and age groups. Emergency Medicaid patients had a poorer overall survival compared to other insurance types though this did not reach statistical significance (p=0.0928). Interestingly, overall survival was similar for patients treated with 1st of 2nd generation TKIs as first line therapy (Median survival not reached, Log rank P value =0.4).
Discussion:
We analyzed CML outcomes and treatment patterns in a large inner city underserved multiethnic cohort in the Bronx. The CML population reflected the ethnic composition of the borough which is predominantly Hispanic and African American. The majority of patients presented in chronic phase CML which is in agreement with other studies. Majority of patients were started on imatinib as first line therapy and had similar overall survival to those that were started on Dasatinib or Nilotinib. The majority of patients who were switched from a first generation TKI to a second generation TKI were due to relapse or lack of adequate response. Our results suggest that TKIs are successfully used in real world populations and are leading to high overall survival even with use of imatinib as first line therapy.

Disclosures
No relevant conflicts of interest to declare.