Characterizing outcomes in severe cytopenias by 3 months in BCMA and CD19 CAR-T cell therapies: A single institution experience.
Authors: Zhuang Tony , Rupji Manali , Santapuram Pranav , Graiser Michael , Romancik Jason , Cohen Jonathon Brett 
Published: June 2023

e19504

Background: Chimeric antigen receptor (CAR) T-cell therapy is approved for treatment in relapsed/refractory diffuse large B cell lymphoma, penta-refractory multiple myeloma (MM), and acute lymphoblastic leukemia. We evaluated relapse and survival rates by 3 months (mo) in patients (pts) who received BCMA and CD19 CAR-T cell therapies. Methods: We performed a retrospective analysis of pts with RRMM and R/R Non-Hodgkin lymphoma (NHL) who received CAR-T cell therapy from 2012-2023 at the Winship Cancer Institute at Emory University. Pts who relapsed prior to 3mo were excluded. SAS was used for statistical analysis with alpha of 0.05. Grades 3/4 cytopenias were compared at day 0, 1mo, and 3mo per CTCAE criteria with each pt counted once if > 1 cytopenia. Hematological recovery was defined as sustained Hgb > 8, Plt > 50,000, and ANC > 1000 without transfusion support. Group differences were evaluated using Chi-Square or Fisher’s exact tests for categorical and ANOVA or Kruskal-Wallis for numerical variables. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method from CAR-T receipt to progression or death, or last known contact for those censored. Univariable and multivariable cox regression were performed. Results: Of 126 pts, 60 had MM and 66 had NHL. Median age at CAR-T receipt was 64yrs (range: 25-85). Fifteen pts had ECOG ≥2. Most pts were male (52.4%) and of white race (61.9%). For R/R NHL, 39.4% received tisa-cel, 33.3% axi-cel, 13.6% brexu-cel, 3.0% liso-cel and 10.6% clinical trial. For RRMM, 91.7% received ide-cel and cilta-cel (8.3%). Bridging therapy, CRS, and ICANS were not associated with severe cytopenias. Overall, 89.7% had grade 3/4 cytopenias at day 0, 54.0% at 1mo, and 34.1% at 3mo. Cytopenia rates, hematological recovery, transfusions, and infectious complications were comparable between groups. Overall, 36.5% required GCSF, 34.9% red cells, 23.0% platelets, and 2.4% TPO. In MM pts, decreased OS was seen with persistence of severe cytopenias (p = 0.009) and decreased PFS with GCSF use ≥2wks (p = 0.007). Time to ANC recovery (days) was more prolonged in MM compared to NHL pts (p = 0.039). Overall median time to recovery (days) was 8, 19, 22.5 for Hgb, ANC, and Plt respectively. On MVA for overall cohort, grade 3/4 cytopenias at 3mo were associated with decreased OS [HR 2.28, 95%CI: (1.22-4.29), p = 0.010) and PFS [HR 1.8, 95%CI: (1.09-2.98), p = 0.022]. On MVA for NHL, decreased OS [HR 2.38, 95%CI: (1.03-5.48), p = 0.043] and PFS [HR 2.11, 95%CI: (1.01-4.41), p = 0.047] were associated with 3mo grade 3/4 cytopenias but not seen in MM pts. Conclusions: We report significant rates of severe cytopenias at 3 months and a potential association with higher relapse and decreased survival rates in pts receiving BCMA and CD19 CAR-T cell therapies. These results are hypothesis generating, and more prospective studies are needed for further confirmation.