Accrual Of Patients With Relapsed and Refractory DLBCL Onto Clinical Trials
Authors: Marton Ashley , Kezouh Abbas , Assouline Sarit 
Published: October 2019

Abstract

Background
New drug development in diffuse large B cell lymphoma (DLBCL) has become a very active area of research in the last several years with the advent of monoclonal antibodies and targeted therapies. We sought to determine the rate of accrual of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) onto early phase clinical trials, and hurdles to their enrolment by performing a retrospective analysis of all DLBCL cases diagnosed at our institution from 01/2006 to 03/2012. This time span represents an active time period for clinical trials in lymphoma at our institution.

Methods
DLBCL cases were identified through the hospital tumor registry. Patients were included in the analysis if they had any diagnosis ofDLBCL relapsed or refractory to standard therapy. Baseline demographics and disease characteristics, details of treatment, responses, relapse, evaluation for clinical trials and participation in clinical trials were determined by review of hospital charts. Only Phase I and II clinical trials were considered for this analysis.

Results
Of a total of 284 patients, 76 had relapsed/refractory disease, 10 of 25 had a successful autologous stem cell transplant (ASCT), and there is insufficient data on 1 patient. Of the remaining 65, 11 (17%) made it to trial. The median age was 65, 34 were male, median number of prior therapies was 2, 74% had at least one comorbidity and 46% had at least 2. Sixty-two percent of patients had de novo DLBCL, 18% transformed and 20% had a composite lymphoma including DLBCL. Reasons for failing to enroll on trial included prohibitive comorbidity (21%), rapid progression (15%), decision for palliation (15%), prior second malignancy (9%), thrombocytopenia (13%), CNS disease (9%), proximity to ASCT (2%), no protocol available(6%), palliative radiation (6%). Patients on trial tended to be younger (58.4 vs. 65.8 years), and to have a lower IPI (mean 3.1 vs 3.4). There was no difference in the number of prior of therapies (2.31 vs. 2.26) or number of comorbidities (2.18 vs 2.21). However, out of the 11 who made it to trial, 7 patients had failed ASCT (46.7% of patients who failed ASCT) vs. 4 (10%) who never had a transplant (p=0.005, Fisher’s exact test). Among the relapsed and refractory cases, 81% of cases were discussed at tumor board.

Conclusions
Although our study is small, we demonstrate that in an active research center, where a large number of R/R DLBCL patients are discussed at tumor board during which information about clinical trials is disseminated, a minority of patients with DLBCL not responding to standard therapy make it to trial.Patients having failed an ASCT are more successfully enrolled onto clinical trials. Interestingly, a similar accrual rate was seen in relapsed non-small cell lung cancer (Baggstrom,J Thor Oncol 2011) and similar barriers to enrolment were found for solid tumor patients (Lara, JCO 2001). Accrual of R/R DLBCL patients onto clinical trials is possible but challenging. A multi-institution analysis is underway.

Disclosures:
No relevant conflicts of interest to declare.