LOW-DOSE CHEMOTHERAPY FOLLOWED BY ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS INDUCES REMISSIONS IN PATIENTS WITH ADVANCED LYMPHOMA
(Abstract release date: 05/19/16)
EHA Library. Goff S. 06/12/16; 135286; S792
Stephanie Goff
Contributions
Contributions
Abstract
Abstract: S792
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in the US and the 5th deadliest cancer with almost 20,000 deaths per year. Anti-CD19 CAR T cells achieve durable remissions in patients with relapsed/refractory B-cell malignancies. Pre-treatment with chemotherapy allows depletion of recipient leukocytes, which improves the anti-cancer effects of adoptively transferred T cells. Increased serum concentrations of interleukin (IL)-15 is believed to contribute to this beneficial effect of chemotherapy. We (Kochenderfer et al. Journal of Clinical Oncology, 2015) and others previously reported effects of high-dose chemotherapy administered before anti-CD19 CAR T-cell therapy. We now report the effects of low-dose conditioning chemotherapy followed by anti-CD19 CAR T-cell infusion.
Aims
The main goals of the study were to evaluate efficacy and safety of low-dose conditioning chemotherapy followed by anti-CD19 CAR T cell therapy in patients with advanced lymphomas.
Methods
Twenty-two patients with advanced lymphoma were included in the study. Eighteen patients were treated with cyclophosphamide 300 mg/m2 daily for 3 days; the remaining 4 patients received cyclophosphamide 500 mg/m2 on this same schedule. Fludarabine 30 mg/m2 was provided to all patients on the same schedule and days as cyclophosphamide. A single dose of CAR T cells was administered 2 days after chemotherapy was completed. CAR T cell concentrations and cytokine levels were examined in blood samples collected from patients. Informed consent was received from all patients.
Results
Among 19 patients with diffuse large B-cell lymphoma of various subtypes, 8 demonstrated complete response, 5 partial response, 2 stable disease, and 4 progressive disease. A complete response was also noted in one patient with mantle cell lymphoma. Two patients with follicular lymphoma both obtained complete response. Duration of response ranged from 1 to 20 months, with 10 remissions that remain ongoing. All but 4 patients had either chemo-refractory lymphoma or relapsed lymphoma following autologous stem cell transplantation. Neurological toxicities were the most commonly observed adverse events. Fever and hypotension were also observed. The median peak blood CAR+ cell concentration was 47/μL (range 4-1217/μL), with higher levels found in patients who demonstrated complete or partial response than in those with stable or progressive disease. The mean serum IL-15 level was 4 pg/mL prior to administration of conditioning chemotherapy and 32 pg/mL after chemotherapy (P < 0.0001).
Conclusion
Low-dose conditioning chemotherapy followed by anti-CD19 CAR T cells induced remissions in patients with advanced B-cell lymphomas.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemotherapy, Immunotherapy, Lymphoma, T cell
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in the US and the 5th deadliest cancer with almost 20,000 deaths per year. Anti-CD19 CAR T cells achieve durable remissions in patients with relapsed/refractory B-cell malignancies. Pre-treatment with chemotherapy allows depletion of recipient leukocytes, which improves the anti-cancer effects of adoptively transferred T cells. Increased serum concentrations of interleukin (IL)-15 is believed to contribute to this beneficial effect of chemotherapy. We (Kochenderfer et al. Journal of Clinical Oncology, 2015) and others previously reported effects of high-dose chemotherapy administered before anti-CD19 CAR T-cell therapy. We now report the effects of low-dose conditioning chemotherapy followed by anti-CD19 CAR T-cell infusion.
Aims
The main goals of the study were to evaluate efficacy and safety of low-dose conditioning chemotherapy followed by anti-CD19 CAR T cell therapy in patients with advanced lymphomas.
Methods
Twenty-two patients with advanced lymphoma were included in the study. Eighteen patients were treated with cyclophosphamide 300 mg/m2 daily for 3 days; the remaining 4 patients received cyclophosphamide 500 mg/m2 on this same schedule. Fludarabine 30 mg/m2 was provided to all patients on the same schedule and days as cyclophosphamide. A single dose of CAR T cells was administered 2 days after chemotherapy was completed. CAR T cell concentrations and cytokine levels were examined in blood samples collected from patients. Informed consent was received from all patients.
Results
Among 19 patients with diffuse large B-cell lymphoma of various subtypes, 8 demonstrated complete response, 5 partial response, 2 stable disease, and 4 progressive disease. A complete response was also noted in one patient with mantle cell lymphoma. Two patients with follicular lymphoma both obtained complete response. Duration of response ranged from 1 to 20 months, with 10 remissions that remain ongoing. All but 4 patients had either chemo-refractory lymphoma or relapsed lymphoma following autologous stem cell transplantation. Neurological toxicities were the most commonly observed adverse events. Fever and hypotension were also observed. The median peak blood CAR+ cell concentration was 47/μL (range 4-1217/μL), with higher levels found in patients who demonstrated complete or partial response than in those with stable or progressive disease. The mean serum IL-15 level was 4 pg/mL prior to administration of conditioning chemotherapy and 32 pg/mL after chemotherapy (P < 0.0001).
Conclusion
Low-dose conditioning chemotherapy followed by anti-CD19 CAR T cells induced remissions in patients with advanced B-cell lymphomas.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemotherapy, Immunotherapy, Lymphoma, T cell
Abstract: S792
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in the US and the 5th deadliest cancer with almost 20,000 deaths per year. Anti-CD19 CAR T cells achieve durable remissions in patients with relapsed/refractory B-cell malignancies. Pre-treatment with chemotherapy allows depletion of recipient leukocytes, which improves the anti-cancer effects of adoptively transferred T cells. Increased serum concentrations of interleukin (IL)-15 is believed to contribute to this beneficial effect of chemotherapy. We (Kochenderfer et al. Journal of Clinical Oncology, 2015) and others previously reported effects of high-dose chemotherapy administered before anti-CD19 CAR T-cell therapy. We now report the effects of low-dose conditioning chemotherapy followed by anti-CD19 CAR T-cell infusion.
Aims
The main goals of the study were to evaluate efficacy and safety of low-dose conditioning chemotherapy followed by anti-CD19 CAR T cell therapy in patients with advanced lymphomas.
Methods
Twenty-two patients with advanced lymphoma were included in the study. Eighteen patients were treated with cyclophosphamide 300 mg/m2 daily for 3 days; the remaining 4 patients received cyclophosphamide 500 mg/m2 on this same schedule. Fludarabine 30 mg/m2 was provided to all patients on the same schedule and days as cyclophosphamide. A single dose of CAR T cells was administered 2 days after chemotherapy was completed. CAR T cell concentrations and cytokine levels were examined in blood samples collected from patients. Informed consent was received from all patients.
Results
Among 19 patients with diffuse large B-cell lymphoma of various subtypes, 8 demonstrated complete response, 5 partial response, 2 stable disease, and 4 progressive disease. A complete response was also noted in one patient with mantle cell lymphoma. Two patients with follicular lymphoma both obtained complete response. Duration of response ranged from 1 to 20 months, with 10 remissions that remain ongoing. All but 4 patients had either chemo-refractory lymphoma or relapsed lymphoma following autologous stem cell transplantation. Neurological toxicities were the most commonly observed adverse events. Fever and hypotension were also observed. The median peak blood CAR+ cell concentration was 47/μL (range 4-1217/μL), with higher levels found in patients who demonstrated complete or partial response than in those with stable or progressive disease. The mean serum IL-15 level was 4 pg/mL prior to administration of conditioning chemotherapy and 32 pg/mL after chemotherapy (P < 0.0001).
Conclusion
Low-dose conditioning chemotherapy followed by anti-CD19 CAR T cells induced remissions in patients with advanced B-cell lymphomas.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemotherapy, Immunotherapy, Lymphoma, T cell
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in the US and the 5th deadliest cancer with almost 20,000 deaths per year. Anti-CD19 CAR T cells achieve durable remissions in patients with relapsed/refractory B-cell malignancies. Pre-treatment with chemotherapy allows depletion of recipient leukocytes, which improves the anti-cancer effects of adoptively transferred T cells. Increased serum concentrations of interleukin (IL)-15 is believed to contribute to this beneficial effect of chemotherapy. We (Kochenderfer et al. Journal of Clinical Oncology, 2015) and others previously reported effects of high-dose chemotherapy administered before anti-CD19 CAR T-cell therapy. We now report the effects of low-dose conditioning chemotherapy followed by anti-CD19 CAR T-cell infusion.
Aims
The main goals of the study were to evaluate efficacy and safety of low-dose conditioning chemotherapy followed by anti-CD19 CAR T cell therapy in patients with advanced lymphomas.
Methods
Twenty-two patients with advanced lymphoma were included in the study. Eighteen patients were treated with cyclophosphamide 300 mg/m2 daily for 3 days; the remaining 4 patients received cyclophosphamide 500 mg/m2 on this same schedule. Fludarabine 30 mg/m2 was provided to all patients on the same schedule and days as cyclophosphamide. A single dose of CAR T cells was administered 2 days after chemotherapy was completed. CAR T cell concentrations and cytokine levels were examined in blood samples collected from patients. Informed consent was received from all patients.
Results
Among 19 patients with diffuse large B-cell lymphoma of various subtypes, 8 demonstrated complete response, 5 partial response, 2 stable disease, and 4 progressive disease. A complete response was also noted in one patient with mantle cell lymphoma. Two patients with follicular lymphoma both obtained complete response. Duration of response ranged from 1 to 20 months, with 10 remissions that remain ongoing. All but 4 patients had either chemo-refractory lymphoma or relapsed lymphoma following autologous stem cell transplantation. Neurological toxicities were the most commonly observed adverse events. Fever and hypotension were also observed. The median peak blood CAR+ cell concentration was 47/μL (range 4-1217/μL), with higher levels found in patients who demonstrated complete or partial response than in those with stable or progressive disease. The mean serum IL-15 level was 4 pg/mL prior to administration of conditioning chemotherapy and 32 pg/mL after chemotherapy (P < 0.0001).
Conclusion
Low-dose conditioning chemotherapy followed by anti-CD19 CAR T cells induced remissions in patients with advanced B-cell lymphomas.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemotherapy, Immunotherapy, Lymphoma, T cell
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