Abstract
INTRODUCTION
In this study, we sought to characterize barriers in enrollment of HIV-positive patients with NHL (DLBCL and PEL), into AMC clinical trials at an academic center in the Bronx.
METHODS
We reviewed an electronic database of HIV-positive patients with NHL, treated at Montefiore Medical Center between 2005 and 2017. Each patient was matched to an AMC trial open at the time of de-novo or relapsed diagnosis. Data on patient demographics, outcomes, and whether a clinical trial was offered, was collected. We recorded information on inclusion/exclusion criteria of matching trials for patients, and reasons for non-enrollment.
RESULTS
There were 128 patients diagnosed with NHL, 55 were excluded due to missing data (treatments/outcomes) and 73 patients were included in the final analysis. Patient demographics are shown in Table 1. Our cohorts predominantly consisted of African-Americans with advanced stage NHL. They were divided into 3 cohorts (Figure 1). Cohort A were patients who met eligibility criteria and were offered a trial (N=14/73 or 19%). Cohort B consisted of patients who were eligible but were not offered a trial (N=15/73 or 21%). Patients in Cohort C did not meet inclusion criteria for available trials (N=44/73 or 60%). Overall enrollment rate was 10%.
Cohort C had the most patients with advanced disease (95%) compared to Cohorts A and B. All patients in Cohorts A and B had ECOG PS 0-2 while in Cohort C, 62% of the patients had ECOG PS 0-2. The IPI score was high-intermediate or high risk for 36% of patients in Cohort A, 40% of patients in Cohort B, and 67% of patients in Cohort C. In Cohort C, 59% of patients received CHOP/EPOCH chemotherapy +/- Rituximab, compared to 87% in Cohort B. There were 29% of patients in Cohort C who did not receive any treatment. In patients who met eligibility criteria, the median OS was not reached at 2 years while for Cohort C the median OS was 12.5 months (p<0.01) (Figure 2).
Most common factors for patient ineligibility were Hepatitis B or C positivity (32%), history of non-compliance (30%) and poor PS secondary to advanced illness (25%) (Figure 3). Based on exclusion criteria of AMC trial 075, 4 patients were excluded given untreated Hepatitis B infection. The criteria did allow patients on Hepatitis B treatment to enroll. AMC trial 047 required patients to be on ARV and consequently 6 patients were ineligible in our cohort.
With the advent of ARV, HIV-positive patients may have less co-morbidities over time, allowing for stricter exclusion criteria. To examine this, we divided Cohort C patients into two groups. Group 1 was diagnosed with NHL from 2005-December 2010 (N=21) and Group 2 from January 2011 to 2017 (N=23). By applying inclusion/exclusion criteria of matching trials, we found Group 1 to have 67% of patients, and Group 2 to have 65% of patients with more than one comorbidity that precluded enrollment.
CONCLUSIONS
This study provides a single institution data on enrollment of HIV NHL patients into clinical trials, in an underserved and predominantly minority population. We found that at diagnosis, 60% of patients did not satisfy inclusion/ exclusion criteria and hence were ineligible, while 40% were eligible for a trial. Application of current AMC eligibility criteria would continue to exclude a significant number of patients. Importantly, 21% of patients were not offered a clinical trial despite meeting all criteria. Reasons for this could include lack of physician awareness or inefficient regulatory processes. Overall survival was significantly higher in patients that met criteria for trials, compared to those that were ineligible.
For 21% of patients who were eligible but not offered a trial, enrollment can be improved by addressing structural barriers and increasing physician awareness. Opportunities to carefully review established/boiler plate eligibility criteria can have a large impact in providing access to trials. We propose the following: Broadening simple eligibility criteria - i.e., including Hepatitis B and C patients; including patients who are not taking ARV; and reflecting carefully on current limits of creatinine, CBC and liver tests applied to AMC NHL trials. In addition, using a comorbidity score to stratify enrollment of patients with advanced disease and poorer PS, rather than excluding them from trials, can be explored. Through modest changes, we can safely increase opportunities for enrollment into clinical trials.
No relevant conflicts of interest to declare.
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