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. 2016 Jan 15;6(2):403–424.

Table 1.

Completed trials of anti-CD19 CAR immunotherapy in B-cell hematological malignancies

Summary of trial Cell number infused Results Toxicities Ref.
Treatment of 2 patients with refractory FL 108/m2 (dose #1) 1 patient showed no response, the other was non-evaluable; limited CAR persistence was noted as a barrier to efficacy Lymphopenia observed in both patients [134]
Lymphodepletion: Flu after dose #1 109/m2 (#2, #3)
Exogenous cytokines: IL-2 2×109/m2 (#4, #5)
Treatment of 6 patients with relapsed or refractory NHL: 1 with SLL, 3 with DLBCL, and 2 with FL/DLBCL Pt 1, 2: 2×107/m2 CD28 costimulation greatly enhanced expansion and persistence of CAR T-cells; 2 patients experienced SD Not reported [48]
Lymphodepletion: None Pt 3, 4: 1×108/m2
Exogenous cytokines: None Pt 4, 5: 2×108/m2
Treatment of 3 patients with relapsed CLL Pt 1: 1.6×107/kg 2 patients obtained CRs, 1 obtained PR Tumor lysis syndrome, lymphopenia, thrombocytopenia, and neutropenia were observed [92,93]
Lymphodepletion: Pt 1: Benda; Pt 2: Benda/Ritux; Pt 3: Pento/Cy Pt 2: 1.0×107/kg
Exogenous cytokines: None Pt 3: 1.5×105/kg
Treatment of 8 patients with relapsed CLL and 2 patients with relapsed ALL 1.8×108-3.2×109 3 of the 4 evaluable CLL patients who received Cy obtained obtained PRs or SD; the 3 CLL patients who did not receive Cy had no response Most patients experienced fevers, B-cell aplasia observed in ALL patient [89]
Lymphodepletion: Six of the patients received Cy
Exogenous cytokines: None
Treatment of 3 patients with relapsed FL, 1 patient with relapsed SMZL, and 4 patients with relapsed CLL 0.3×107/kg-3.0×107/kg 5 of the 7 evaluable patients obtained PRs, one obtained CR Cytokine-associated toxicities including hypotension, fevers, fatigue, renal failure, and obtundation [90,91]
Lymphodepletion: Flu/Cy
Exogenous cytokines: IL-2
Treatment of 8 patients with relapsed ALL or CLL who had received prior HSCT 1.9×107-1.1×108 3 patients obtained CRs, 1 obtained PR, 1 experienced SD No infusion-related toxicities [135]
Lymphodepletion: None
Exogenous cytokines: None
Treatment of 10 patients with relapsed CLL, DLBCL, and MCL who had received prior HSCT and DLI 0.4×106/kg-7.8×106/kg 1 patient obtained CR, 1 obtained PR, 6 experienced SD Toxicities included transient hypotension and fever [136]
Lymphodepletion: None
Exogenous cytokines: None
Treatment of 2 children with relapsed and refractory ALL Pt 1: 1.4×106/kg Both patients obtained CRs Cytokine release syndrome and B-cell aplasia were observed in both patients [95]
Lymphodepletion: Pt 1: None; Pt 2: Cy/VP16 Pt 2: 1.2×107/kg
Exogenous cytokines: None
Treatment of 16 patients with relapsed of refractory ALL 3.0×106/kg 88% of patients obtained CRs 7 patients experienced severe cytokine release syndrome, some patients experienced neurologic toxic effects [54]
Lymphodepletion: Cy
Exogenous cytokines: None
Treatment of 30 patients with relapsed or refractory ALL 0.8×106/kg-1.7×107/kg 90% of patients obtained CRs 8 patients experienced sever cytokine release syndrome, some patients experienced neurologic toxic effects [53]
Lymphodepletion: 15 patients received Flu/Cy, 12 received a different lymphodepletion regimen
Exogenous cytokines: None
Treatment of 14 patients with relapsed or refractory B-cell malignancies Not reported Cells cultured with IL-7 and IL-15 prior to infusion showed greater persistence and efficacy in vivo than those cultured in IL-2 None reported [137]
Lymphodepletion: None
Exogenous cytokines: None
Treatment of 21 patients with relapsed of refractory ALL or NHL Most patients received 1×106/kg (maximum tolerated dose), four received a second dose at 3×106/kg 67% of patients obtained CRs 3 patients experienced sever cytokine release syndrome [138]
Lymphodepletion: Flu/Cy
Exogenous cytokines: None
Treatment of 15 patients with relapsed of refractory B-cell malignancies: 9 with DLBCL, 2 with indolent lymphomas, and 4 with CLL 1×106/kg-5×106/kg 8 of the 13 evaluable patients obtained CRs, 4 obtained PRs, 1 experienced SD Toxicities in some patients including fever, hypotension, delirium, and other neurologic toxicities; 1 patient died suddenly due to an unknown cause 16 days after cell infusion [94]
Lymphodepletion: Flu/Cy
Exogenous cytokines: None
Treatment of a patient with refractory multiple myeloma as an addition to high-dose melphalan and HSCT 5×107 Durable CR was obtained; enhanced response attributed to anti-CD19 CAR T-cell activity Hypogammaglobulinemia was observed [139]
Lymphodepletion: Cy
Exogenous cytokines: None
Treatment of 29 patients with relapsed or refractory NHL: 19 with DLBCL, 8 with FL, and 2 with MCL 5×108 Of the 18 evaluable patients, overall response rate was 50% for DLBLC patients and 100% for FL patients 15 patients experienced cytokine release syndrome, 3 patients experienced neurologic toxic effects [140]
Lymphodepletion: Cy, Benda, EPOCH, radiation/Cy, or Flu/Cy
Exogenous cytokines: None
Treatment of 7 patients with relapsed or refractory NHL after HDT-ASCT 7 patients received 5×106/kg, 1 received 1×107/kg 5 patients obtained CRs One patient experienced prolonged cytopenias and died of mucormycosis pneumonia 38 days after HDT-ASCT; 4 patients experienced cytokine release syndrome [141]
Lymphodepletion: BEAM
Exogenous cytokines: None

ALL: acute lymphocytic leukemia; ASCT: autologous hematopoietic stem cell transplantation; BEAM: carmustine, etoposide, cytarabine, and melphalan; Benda: bendamustine; Ritux: rituximab; CLL: chronic lymphocytic leukemia; CR: complete response; Cy: Cyclophosphamide; DLBC: diffuse large B-cell lymphoma; DLI: donor lymphocyte infusion; EPOCH: etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin; FL: follicular lymphoma; Flu: fludarabine; HDT: high-dose therapy; MCL: mantle cell lymphoma; NHL: non-Hodgkin’s lymphoma; Pento: pentostatin; PR: partial response; SD: stable disease; SLL: small lymphocytic lymphoma; SMZL, splenic marginal zone lymphoma; VP-16: etoposide.