Abstract
CAR T-cell therapy has changed the landscape of relapsed-refractory non-Hodgkin lymphoma and multiple myeloma (MM). While cytokine release syndrome and neurological toxicities (ICANS) are well known, information on prolonged cytopenia and immune dysregulation is very limited. Since the majority of CAR T-cell trials had underrepresentation of African-American (AA) patients, the impact of race on the pattern of cytopenia is not known. In this study, we investigate post-CAR-T cytopenia with a focus on racial differences in hematologic toxicities.
We conducted a retrospective analysis of patients (pts) who received CD19- or BCMA-targeted CAR T-cell therapy for diffuse large B-cell lymphoma (DLBCL) or MM at Karmanos Cancer Center between 2016 and 2024. Baseline demographic and clinical characteristics were collected. Hematologic parameters were compared among AA and non-AA pt populations at various time points, such as before CAR T cell collection and at 1,2,3,6, and 12 months following CAR T-cell infusion or until relapse, requiring additional treatment. Cytopenia was graded according to CTCAE v5.0 criteria. Various clinical parameters were compared among these two cohorts and analyzed using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Overall survival (OS) was defined as the time from CAR-T administration to death from any cause. Relapse-free survival (RFS) was defined as the time from CAR-T administration to documented relapse or death, whichever occurred first. Kaplan Meier methods were used to estimate survival distributions for OS and RFS. Follow-up time was estimated using the reverse Kaplan–Meier method.
A total of 174 adult pts received CAR T-cell therapy, including 59% with DLBCL and 41% with MM. Our cohort was 79% Caucasian, 15% AA, 2% Asian, 1% Hispanic, and 3% other. Among AA pts, 73% of AA pts had MM compared to 35% of non-AA pts (p < 0.001), while DLBCL was more frequent in non-AA pts (64% vs. 26%). Most pts were aged 60–80 years(yrs) (65% of AA vs. 58% of non-AA), and approximately 80% in both groups had a performance status of 70–80% (p = 0.92). ICANS occurred in 27% of non-AA pts and 15% of AA pts (p = 0.23), while the incidence of CRS was similar (69% in both groups). However, use of steroids for ICANS was significantly lower in AA pts compared to non-AA pts (50% vs. 95%, p = 0.036). CAR T-cell product distribution differed by race: AA pts more often received cilta-cel (35%) and non-approved or investigational products (23%), while non-AA pts predominantly received Axi-cel (44.6%). Post-infusion, AA pts had significantly lower median absolute neutrophil counts (ANC) at day 30 (1.10 vs. 1.45 ×10⁹/L; p = 0.017), day 90 (1.80 vs. 2.65 ×10⁹/L; p = 0.031), and day 365 (2.00 vs. 2.90 ×10⁹/L; p = 0.033). At day 30, 92.3% of AA pts had neutropenia: grade 1 in 6 (23.1%), grade 2 in 10 (38.5%), and grade ≥3 in 8 (30.8%), compared to 77.7% of non-AA pts with grade 1 in 37 (25.0%), grade 2 in 36 (24.3%), and grade ≥3 in 42 (28.3%). By day 90, 46.2% of AA pts had persistent neutropenia (grade 1–3), versus 36.5% of non-AA pts. At one yr, 19.2% of AA pts continued to exhibit low-grade neutropenia (grade 1–2), compared to 14.9% of non-AA patients, while normalization of absolute neutrophil count (ANC) was observed in 80.8% and 85.1% of AA and non-AA pts, respectively. This trend was not observed in hemoglobin or platelet countat similar time points. Our cohort did not show significant differences in baseline ANC by race, hemoglobin, or platelet counts. Additionally, no AA patients developed secondary hematologic malignancies, while 7 non-AA patients did (five with MDS, one with AML, one with aplastic anemia). The incidence of infection within 100 days was similar between groups (30.4% in non-AA vs. 26.9% in AA; p = 0.82). ICU admission occurred in 13.5% of non-AA pts and 3.8% of AA pts (p = 0.32). 2-yr overall survival was 61% (95% CI, 2.15–NR) for non-AA and 71% (95% CI, 1.97–NR) for AA pts (HR 0.95; 95% CI, 0.48–1.86; p = 0.88). 2-yr relapse-free survival was 45% (95% CI, 0.94–3.12) in non-AA and 58% (95% CI, 0.61–NR) in AA pts.
Our findings highlight a pattern of delayed neutrophil recovery following CAR-T therapy among Black patients with DLBCL and MM. These observations emphasize the need for early recognition and to consider starting supportive treatments sooner and more aggressively in this population.
