Introduction: CAR T therapy has improved overall survival for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who otherwise have poor outcomes with traditional chemoimmunotherapy. Cytokine release syndrome (CRS) and neurotoxicity are well known side effect from CAR T therapy. Cytopenia has been reported as well. However, to our knowledge, transfusion requirements during the first 30 days post-CAR T treatment have not been reported. Here we report the cytopenia characteristics and transfusion requirements in 15 patients who received commercial Axicabtagene ciloleucel (Yescarta) CAR-T cell therapy.
Methods: We retrospectively reviewed all DLBCL patients who received Yescarta between July 2018 through May 2019 at Weill Cornell Medical Center. All patients received cyclophosphamide (500mg/m2) and fludarabine (30mg/m2) lymphodepleting regimen from days -5 to -3 before the CAR T cell infusion. Cytopenia, granulocyte-colony stimulating factor (G-CSF) use, packed red blood cell (RBC) and platelet transfusion requirements during 30 days after CAR T infusion were examined. Cytopenia was defined according to CTCAE criteria. Grade 3 cytopenia was white blood cell (WBC) <2 x 103/mL, absolute neutrophil count (ANC) <1 × 103/mL, hemoglobin (Hb )<8 g/dL or platelet count <50 × 103/mL. Grade 4 cytopenia was white blood cell (WBC) <1 x 103/mL, absolute neutrophil count (ANC) <0.5 × 103/mL, hemoglobin (Hb )<6.5 g/dL or platelet count <25 × 103/mL.
Results: Median age was 68 years (range, 21-86yr) with 53% males (Table 1). Ten patients (67%) experienced cytokine release syndrome (CRS) with 8 patients receiving at least 1 dose of tocilizumab. Five patients (33%) experienced immune cell-associated neurologic syndrome (ICANS) and all received dexamethasone. Among patients with ICANS, one required ventilation support, one had a focal seizure and one had cerebellar ischemic stroke. Ten (70%) of the 14 evaluable patients had a D30 restaging PET/CT. Two patients had progressive disease and12 patients achieved partial response (PR).
On admission, grade 3 or 4 leukopenia or neutropenia was observed in 0 patients, except 1 patient (WBC14.1, but ANC 0). There were 2 patients had grade 3 anemia, none of the patients had grade 4 anemia or grade 3/4 thrombocytopenia. Between D0 and D30, grade 3 or 4 leukopenia or neutropenia was observed in 12 patients (Figure 1). Grade 3 or 4 anemia was observed in 6 and 5 patients and grade 3 or 4 thrombocytopenia in 9 and 6 patients respectively. A total of 6 patients (43%) required G-CSF, 6 (43%) and 6 (43%) patients required red blood cell transfusion and/or platelet transfusion support. The median PRBC and platelet transfusion was 0 (range, 0-8) and 0 (range, 0-19). Three (20%) of the 15 patients accounted for the majority of the transfusion support.
Conclusion: Cytopenia was common during the first 30 days after CAR-T cell therapy. Although nearly half of the patients required G-CSF and transfusion support, few patients had a significant burden.
Van Besien:Miltenyi Biotec: Research Funding.
