6536 Background: Contemporary precision medicine trials in DLBCL often require real-time central pathology review for enrollment. Central review may lead to treatment delays and prevent high risk patients (pts) with aggressive presentations from enrolling onto clinical trials. We explored reasons pts with DLBCL were not enrolled on trials and the implication of non-enrollment on trial design and interpretation. Methods: We retrospectively analyzed all pts with histologic diagnosis of DLBCL or HGBL from 4/14 to 6/16 at the University of Rochester. Therapeutic trials open during this time included 3 sponsored and 2 NCTN studies. The Kaplan-Meier method was used to estimate the distribution of progression-free survival (PFS; time from start of treatment until progression/death or until the last date the patient was known to be progression free) and overall survival (OS). Results: 140 pts were identified; 22% enrolled on a trial. Reasons for non-enrollment included: 1) Protocol ineligibility (n=58); (2) Physician choice (n=24) and; 3) Patient choice (n=20). Reasons were unclear in 8 pts. Of the 24 pts who were not enrolled due to physician choice, 21 required urgent treatment secondary to symptoms or rapid progression. Compared to pts treated on trial, pts with rapid progression had higher risk clinical features (table). There was a trend towards a lower 1-year PFS rate in pts who required urgent treatment compared to those on trial (72.1% vs. 56.1%; p=0.08). There was no statistical difference in OS. Conclusions: At our institution, for patients with DLBCL meeting trial eligibility criteria, 42% required urgent chemotherapy and failed to enroll. Exclusion of these high risk patients in precision medicine trials has important implications in the interpretation and generalizability of clinical trials in DLBCL. In this curable malignancy, excluding high risk patients from trials limits the event rate, and associated power to demonstrate impact of novel therapies. [Table: see text]
Need for multiple risk reduction strategies in clinical trials enrolling high risk patients - FOURIER investigating PCSK-9 inhibitor to lower cholesterol revisited