Outcomes of Patients Underrepresented in Pivotal Trials of Anti-CD19 CAR-T Cell Therapy

Three commercial anti-CD19 chimeric antigen receptor modified T-cell therapies (CAR-T) were approved for the treatment of chemo-refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) based on results from pivotal registration trials that had strict inclusion and exclusion criteria. Additionally, despite enrollment across multiple large centers, underrepresented minorities (URMs) accounted for a small portion of the trial participants (e.g., only 11% enrolled to ZUMA1 were non-White). Therefore, there is an unmet need to compare the outcomes of those who were represented in the pivotal trials with those who would have been excluded based on eligibility criteria and those populations that had poor representation. Our cancer center serves a diverse catchment area inclusive of Harris County, where approximately 65% of residents identify as URMs (20% African Americans, 45% Hispanics). Thus, we are ideally located to study outcomes of URMs.We reviewed outcomes of the first 61 patients with lymphoma that were treated with commercial CAR-T cells at our center.Of the 61 patients, 18 (30%) were Hispanic, 7 (11%) Black, and 5 (8%) Asian. Only 24 (39%) would have been eligible for the initial trials while 37 (61%) would have been excluded. The main reasons for exclusion were inadequate bone marrow reserve in 14 patients, recent systemic or radiation therapy in 11, and inadequate renal function in 7. Out of the 37 excluded, 16 would have been excluded by two or more criteria. At the time of data analysis, 37 (61%) had progressed and 22 (36%) had died. There was no difference between groups in ≥ grade 3 immune effector mediated toxicity rates (13% “included group” vs. 14% “excluded group” and 10% URMs vs. 16% Whites). While there were no statistical differences in progression free survival (PFS) between both groups, overall survival (OS) was decreased in patients that would have been excluded (OS at 1 year = 82% for included group and 59% for excluded group, p = 0.034). The URM subgroup had similar PFS (p = 0.441) and 1-year OS to White patients (65% for URMs vs. 71% for Whites, p = 0.144).Although sample sizes are small, anti-CD19 CAR-T cell therapy proved to be an effective treatment for chemo-refractory DLBCL and FL regardless of trial eligibility at our center. Interestingly, OS appears to be worse in trial ineligible patients indicating that the strict enrollment criteria for these trials, as expected, excluded patients with shortened lifespans from co-morbidities. Similarly, URMs tend to have similar CAR-T efficacy and toxicity outcomes to those enrolled in the pivotal registration trials.