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CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope.

ABSTRACT: Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to refractory disease, lack of a suitable allogeneic donor, higher age, or cumulative toxicity of previous chemotherapy. Despite patients undergoing allogeneic HCT normally profit from a graft-versus-lymphoma effect, overall survival in patients with NHL after HCT remains short. Therefore, novel treatment modalities are urgently needed. Chimeric antigen receptor (CAR)-T cells, a new class of cellular immunotherapy involving ex vivo genetic modification of T cells to incorporate an engineered CAR have been used in clinical trials. In the majority of studies, B cell malignancies treated with CD19 targeting CAR-T cells have been analyzed. Recently, results from 2 CD19 directed CAR-T cell trials with an increased follow-up of patients led to Food and Drug Administration and European Medicines Agency approval of tisagenlecleucel and axicabtagene ciloleucel. Common adverse events (AEs) include cytokine release syndrome and neurological toxicity, which may require admission to an intensive care unit, B cell aplasia and hemophagocytic lymphohistiocytosis. These AEs are manageable when treated by an appropriately trained team following established algorithm. In this review, we summarize the results of 3 large phase II CD19 CAR-T cell trials and focus on AEs. We also provide a perspective of ongoing activity in this field with the intend to improve the potency of this emerging novel therapy.

SUBMITTER: Hopfinger G

PROVIDER: S-EPMC6746029 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope.

Hopfinger Georg G Jäger Ulrich U Worel Nina N

HemaSphere 20190308 2

Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to refractory disease, lack of a suitable allogeneic donor, higher age, or cumulative toxicity of previous chemotherapy. Despite patients undergoing allogeneic HCT normally profit from a graft-versus-lympho ...[more]

PMID: 31723824

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Project description:PurposeAxicabtagene ciloleucel (axi-cel) is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma. Bridging therapy may be required for lymphoma control during the manufacturing interval between collection of autologous T cells and final CAR T product administration. The optimal bridging therapy is not known and patients are often chemorefractory. We present a case series of patients receiving radiation as a bridge to axi-cel.Methods and materialsBetween December 2017 and October 2018, 12 patients were intended to receive bridging radiation before axi-cel. The group was characterized by highly aggressive disease including 6 of 12 with "double hit" lymphoma and 6 of 12 with disease ≥10 cm in diameter. All patients received 2 to 4 Gy/fraction to a median dose of 20 Gy (range, 6-36.5 Gy). Half of patients received either 30 Gy in 10 fractions or 20 Gy in 5 fractions. Seven patients received concurrent chemotherapy. Eleven patients underwent axi-cel infusion and one did not. Median follow-up was 3.3 months (range, 1.1-12.0 months).ResultsNo significant toxicities were identified during bridging radiation, and no patient experienced in-field progression of disease before axi-cel infusion. One patient experienced abdominal pain, which resolved after dose reduction. Two patients had out-of-field progression of disease during the bridging period. After axi-cel infusion, 3 of 11 patients (27%) experienced severe cytokine release syndrome or neurotoxicity. At 30 days, the objective response rate was 81.8% (11 of 12 evaluable; 1 stable disease, 1 out-of-field progression), with complete response in 27% (3 of 11). At last follow-up, the best objective response rate was 81.8%, with a complete response attained in 45% (5 of 11). Lymphocyte counts decreased slightly in 10 of 12 patients during radiation (median, 0.25 k/uL).ConclusionsRadiation (with or without concurrent chemotherapy) can be safely administered as a bridge to axi-cel in high-risk lymphoma. Caution should be taken if irradiation is started before apheresis, and lymphocyte counts should be monitored closely throughout. Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy.

Dataset Information

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope.

Publications

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope.

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