Hematologic Toxicities of CAR T-Cell Therapy in Non-Hodgkin Lymphoma

Chimeric Antigen Receptor T-Cell (CART) therapy remains a novel approach for the treatment of relapsed, refractory B-cell Lymphoma. Complications of CAR T-cell therapy including cytopenias, infections, cytokine release syndrome (CRS) and neurotoxicity require aggressive supportive care. The objective of this study was to characterize the incidence of cytopenias and the utilization of growth factor and transfusion support following CAR T-cell therapy. This retrospective, single center study included 38 patients with relapsed, refractory non-Hodgkin lymphoma (NHL), who received CD19 directed CAR T-cell therapy, axicabtagene ciloleucel, as standard of care for the treatment relapsed NHL between January, 2018 and October, 2019. Cytopenias included 34% grade 4 thrombocytopenia (13/38), 76% grade ≥3 anemia (29/38), and 92% grade 4 neutropenia (35/38). Thirty-four percent (13/38) of patients required platelet transfusion support, 76% of patients (29/38) required RBC transfusions, 92% (35/38) of patients became neutropenic and 81.6% (31/38) received growth factor support. Twenty-nine percent of patients were found to have recurrent neutropenia status post recovery of their initial onset. The median initial onset occurred on day +8 (0-+14) and lasted a median of 5 days (0-85 days) with a median ANC nadir of too few cells to count (0-490). The median onset for a 2nd occurrence of neutropenia occurred on day +21 (D+12- D+28) which lasted 1 day (1-11 days) with a nadir of 430 cells/mm3 (0-480). Sixteen percent of patients experienced a 3rd occurrence on day +35 (D+25-+52), lasting a median of 3.5 days (1-19 days) with a median nadir of 335 cells/mm3 (270-440). One patient had a 4th occurrence on day +28 with a nadir of 220 cells/mm3. The etiology of recurrent neutropenia described is unclear. Multiple factors may contribute including bridging therapy, infection, steroids, CRS, and growth factor support. More is data is needed to identify risk factors for recurrent neutropenia. Chimeric Antigen Receptor T-Cell (CART) therapy remains a novel approach for the treatment of relapsed, refractory B-cell Lymphoma. Complications of CAR T-cell therapy including cytopenias, infections, cytokine release syndrome (CRS) and neurotoxicity require aggressive supportive care. The objective of this study was to characterize the incidence of cytopenias and the utilization of growth factor and transfusion support following CAR T-cell therapy. This retrospective, single center study included 38 patients with relapsed, refractory non-Hodgkin lymphoma (NHL), who received CD19 directed CAR T-cell therapy, axicabtagene ciloleucel, as standard of care for the treatment relapsed NHL between January, 2018 and October, 2019. Cytopenias included 34% grade 4 thrombocytopenia (13/38), 76% grade ≥3 anemia (29/38), and 92% grade 4 neutropenia (35/38). Thirty-four percent (13/38) of patients required platelet transfusion support, 76% of patients (29/38) required RBC transfusions, 92% (35/38) of patients became neutropenic and 81.6% (31/38) received growth factor support. Twenty-nine percent of patients were found to have recurrent neutropenia status post recovery of their initial onset. The median initial onset occurred on day +8 (0-+14) and lasted a median of 5 days (0-85 days) with a median ANC nadir of too few cells to count (0-490). The median onset for a 2nd occurrence of neutropenia occurred on day +21 (D+12- D+28) which lasted 1 day (1-11 days) with a nadir of 430 cells/mm3 (0-480). Sixteen percent of patients experienced a 3rd occurrence on day +35 (D+25-+52), lasting a median of 3.5 days (1-19 days) with a median nadir of 335 cells/mm3 (270-440). One patient had a 4th occurrence on day +28 with a nadir of 220 cells/mm3. The etiology of recurrent neutropenia described is unclear. Multiple factors may contribute including bridging therapy, infection, steroids, CRS, and growth factor support. More is data is needed to identify risk factors for recurrent neutropenia. Tables 1 and 2.Table 1Baseline CharacteristicsN=38Age (years)56 (30-74)Male26/38 (68.4%)Female12/38 (31.6%)Subtype of NHL• DLBCL19/38 (50%)• TFL13/38 (34%)• High grade Lymphoma5/38 (13%)• PMBCL1/38 (2.6%)Hematologic Parameters• Platelets116 (23-614)• ANC3.2 (0-7.9)• Hgb10.3 (7.4-13.2)• CD4116 (23-614) Open table in a new tab Table 2Incidence, onset and duration of NeutropeniaNeutropenia <5001st Occurrence2nd Occurrence3rd Occurrence4th OccurrenceIncidence35/38 (92%)11/38 (29%)6/38(16%)1/38 (2.3%)Duration of ANC<5005d (0-85d)1 d (1-11d)3.5 d (1-19 d)1 dOnset of NeutropeniaD+8 (0-+14)D+21 (D+12-D+28)D+38 (D+25-D+52)D+28Time to NadirD+9 (D+3-D+15)D-26 (D+12-D+54)D+35 (D+29-D+37)D+28ANC at Nadir0 (0-490)430 (0-480)335 (270-440)220Recovery of ANC >500D+7 (D+5-D+9)D+27 (D+13-CM-65)D+41 (D+26-D+59)D+29Duration of G-CSF6 d (1-41 d)3 d (1-18)3 d (1-11)ND Open table in a new tab