Up-Regulation of CAR-T Cells after G-CSF and Dexamethasone Treatment in a Defuse Large B Cell Lymphoma Patient Receiving 4SCAR19 T Cell Therapy

A 37-year-old woman was diagnosed with DLBCL, GCB origin, positive with CD20, Bcl-2, Bcl-6, CD10 and negative with CD3, CD5, ,D21, CD23, CyclinD1. PET-CT scan showed that her lymph nodes were broadly involved. Based on PET-CT, the stage was IIIA and aaIPI score was 1. After eight cycles of R-CHOP (rituximab, cyclophosphamide, epirubicin, vincristine, and prednisone), the tumor regressed to a small retroperitoneum lesion with SUV 2.0, and she received another four cycles of rituximab for maintenance. The tumor relapsed one year later with resistance to ESHAP after she had failed multiple alternative treatments including GA101 trial, 3x DICE, MTX1g, 2x GEMOX, and 2x EPOCH. She was enrolled in a CD19-CAR (chimeric antigen receptor) T cell pilot study in January 2015. Her T cells were apheresis collected and transduced with a 4^th generation, apoptosis-inducible, safety-engineered lentiviral CAR: CD19- scFv/CD28/CD137/CD27/CD3ζ-iCasp9 (4SCAR19). A personalized conditioning regimen was given based on the patient's history to chemotherapy: cyclophosphamide 500mg/d d1-3, and fludarabine 50mg/d d1-4, 40mg d5. Two days later, she received infusions of a total dose of 1.27×10⁸ of the 4SCAR19 T cells (2x10⁶/kg). At day 7 (D7) after infusion, she developed a fever over 39^o C, which lasted for 7 days; this was controlled with NSAIDs (Non-Steroidal Anti-inflammatory Drugs). The tumor in her lymph nodes began to shrink 5 days after CAR-T infusion and she achieved nCR (near complete response) after 30 days. In a follow up PET/CT 3 months after CAR-T infusion, there was only one suspected retroperitoneum lesion (SUV 3.8) in the whole body, but it was indiscernable whether the SUV signal was tumor or T cell related. We monitored the peripheral blood CAR-T cell counts by qPCR and detected 0.03%, 0.07%, 0.3%, 9.3%, 0.01%, 1.57% on D7, D13, D48, D69, D84 and D112, respectively. In attempt to perform an autotransplantation to pursue a cure, she was mobilized twice with G-CSF on D68-D72, D110-112, plus dexamethasone 20mg/d on D101-102 and 15 mg/d on D110-111. Unexpectedly, the CAR-T cells in the patient peripheral blood increased to 9% after the first mobilization, and to 18% after the second mobilization. To this date, the patient has remained in nCR after 4SCAR19 therapy (January 23 to July 23, 2015). To our knowledge, this is the first report of evident CAR-T cell boost associated with G-CSF plus dexamethasone treatment. Further investigation is warranted to understand the molecular mechanisms behind such a favorable CAR-T therapy outcome in a terminal DLBCL disease.