The Outcome of Patients (pts) with Chronic Myeloid Leukemia (CML) Treated with Imatinib Outside of a Clinical Trial or On a Clinical Trial At a Single Institution
Authors: Yilmaz Musa , Kantarjian Hagop M. , Jabbour Elias J. , O'Brien Susan M. , Borthakur Gautam , Verstovsek Srdan , Garcia-Manero Guillermo , Ravandi Farhad , Burger Jan A. , Pierce Sherry A. , Quintás-Cardama Alfonso , Cortes Jorge E. 
Published: October 2019

Abstract
Abstract 1693

Background:
Outcomes of CML chronic phase (CP) pts treated in clinical trials are frequently perceived to not be representative of those treated outside of clinical trials (Lucas et al, Haematologica 2009; 94: 1362–7). The latter is frequently referred to as “the real world” world experience. Some reports have suggested that outcome of pts treated outside of clinical trials have an inferior outcome. We investigated the outcomes of pts receiving imatinib on and off a clinical trial for CML-CP at a single institution.

Methods:
We reviewed the medical records of all pts with CML-CP treated at MDACC between 2000 and 2012 to identify pts that received initial therapy with imatinib 400 mg on a clinical trial or as standard therapy outside of a clinical trial (“off protocol” group). Only pts who had not received any prior therapy, or only hydroxyurea, or interferon alpha for less than 1 month, and that initiated on 400 milligram daily dose of imatinib within 6 months of diagnosis were included. Event-free survival (EFS) was measured from the start of treatment to the date of any of the following events: loss of major cytogenetic response (MCyR), loss of complete hematologic response (CHR), transformation to accelerated phase (AP) and blast phase (BP), and death while on imatinib. Transformation-free survival (TFS) was measured from the start of treatment to the date progression to AP/BP during therapy, last follow-up, or death from any cause. Overall survival (OS) was measured until death form any cause at any time.

Results:
We identified 65 pts treated with imatinib off protocol during the period of interest. During this time 71 pts were treated on clinical trials with imatinib. The median age was 49 yrs (15–79) for pts on clinical trials and 49 yrs (15–84) for those off protocol, respectively. The median follow-up was 125 months (13 to 142) for pts on clinical trials and 51 months (2 to 117) for those off protocol. The overall complete cytogenetic response (CCyR) rates were 84% and 83% for patients treated on and off protocol, respectively. CCyR rates, 12 months after initiation of imatinib, were not different (60% vs 66%, respectively; p=.15). Pts treated on protocol had higher rates of major molecular response (MMR) (79% vs 58%, P=.012) and complete molecular response (CMR = undetectable with sensitivity of at least 4 logs) (42% vs 32%, P=.045) at any time compared to the pts treated off protocol. This is likely due to the longer follow-up for pts on protocol as MMR takes longer to occur. In fact, the MMR rate at 12 months were 30% and 24% in pts treated on and off protocol, respectively (p=.28). Analyzing earlier responses, 3-month rates of MCyR were 71% on protocol and 69% off protocol (p=.82). Corresponding rates at 6 months were 82% and 85%, respectively (p=.68). The 5-year EFS rates were 86% and 84% for on and off protocol patients, respectively. There was also no significant difference in 5-year TFS (96% vs 94%) and OS (90% vs 96%).

Conclusion:
These results suggest that pts with CML treated outside of a clinical trial may have the same excellent outcome as those treated on a clinical trial provided they are followed with the same rigor.

Disclosures:
Ravandi: BMS: Research Funding. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.