Analysis of Outcomes In Adolescents and Young Adults (AYA) with Chronic Myeloid Leukemia (CML) Treated with Upfront Tyrosine Kinase Inhibitors (TKI)
Authors: Pemmaraju Naveen , Kantarjian Hagop , Shan Jianqin , Jabbour Elias , Quintas-Cardama Alfonso , Verstovsek Srdan , Ravandi Farhad , Wierda William G. , O'Brien Susan , Cortes Jorge E. 
Published: October 2019

Abstract
Abstract 1234

Background:
Outcomes in CML have dramatically improved since the introduction of upfront treatment with first (imatinib) and second generation (dasatinib, nilotinib) TKIs. The median age of diagnosis of CML is approximately 67 years (yrs). However, there is a small, but significant group of patients (pts) diagnosed with CML at a significantly younger age, especially those age 15–21, or AYA pts. Historically, stem cell transplantation was employed as an initial treatment strategy in many CML AYA pts. Little is known about the outcomes of this AYA group of CML pts in the TKI era.

Objective:
To determine the characteristics and outcomes of CML AYA pts in the era of upfront treatment with TKI.

Methods:
We reviewed the records of all CML pts treated at our institution on clinical protocols with upfront TKI treatments from July 2000-April 2010. AYA pts were defined as age 15–21. No pts receiving upfront SCT were included in this analysis.

Result:
A total of 435 CML pts have been prospectively followed on protocol from 7/2000-4/2010. Patients were included in sequential or parallel trials with identical inclusion criteria: 1) Imatinib (281 pts), 2) Nilotinib (78 pts), and 3) Dasatinib (76 pts). The median age of the entire cohort was 48 yrs (15-85 yrs). Median follow up time for the entire cohort was 67 months (mo) (2-116 mo) with median treatment time 49 mo (0.1-114.9 mo). We identified 13 AYA pts for analysis in this study. There were no significant differences between the AYA pts and the older pts with regard to baseline splenomegaly, platelet count, or blast counts. There was an expected trend for more AYA patients being in the low Sokal risk group (as age is one of the factors in Sokal risk), but it was not statistically significant. The only significant differences between AYA pts and older pts was median baseline Hemoglobin levels (11.3 g/dL in AYA group vs 12.4 g/dL in older group, p=0.04) and in baseline median WBC (6.8 × 109/L for AYA group vs 28.2 × 109/L in older group, p=0.02). In the AYA group: 2 pts have had stem cell transplants (SCT) after failing upfront TKI. Only one pt has died (pt experienced TKI resistance and then developed GVHD after cord blood transplant) in the AYA group. Eight of total 13 AYA pts have been taken off TKI (2 TKI resistance, 2 lost to follow-up, 3 toxicity of TKI, 1 SCT). For comparison of outcomes by age group of AYA pts and for pts >21 yrs, see Table 1 below:

Conclusions:
At median follow up of 67 months and med treatment time of 49 months, we found the rate of CCyR was significantly higher in older pts compared to AYA pts, and trended towards significance favoring older pts with rates of MMR and CMR (as shown in Table 1). The EFS, TFS, and OS among the two groups showed no significant differences. Although these are small numbers of AYA pts, the observation of higher MMR, CCyR and CMR rates in older, rather than younger, pts is unexpected. The factors that contribute to this observation need to be determined (eg, compliance). Additional observations in this patient population are warranted to better define their outcome and make proper treatment recommendations.

Disclosures:
Off Label Use: Dasatinib as treatment for upfront, frontline treatment of CML. Kantarjian:BMS, Pfizer and Novartis: Research Funding; Novartis: Consultancy. Verstovsek:Incyte Corporation: Research Funding. Ravandi:Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau. Wierda:GlaxoSmithKline: Honoraria, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cortes:Pfizer: Consultancy, Research Funding; BMS: Honoraria, Research Funding; Novarits: Honoraria, Research Funding.