LOW-DOSE CHEMOTHERAPY FOLLOWED BY ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS INDUCES REMISSIONS IN PATIENTS WITH ADVANCED LYMPHOMA
Author(s): ,
James N Kochenderfer
Affiliations:
Experimental Transplantation and Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH),Bethesda,United States
,
Robert PT Somerville
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Tangying Lu
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Victoria Shi
Affiliations:
Experimental Transplantation and Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH),Bethesda,United States
,
James C Yang
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Richard M Sherry
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Christopher A Klebanoff
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Udai S Kamula
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Stephanie L Goff
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Adrian Bot
Affiliations:
Kite Pharma, Inc.,Santa Monica,United States
,
John Rossi
Affiliations:
Kite Pharma, Inc.,Santa Monica,United States
,
Marika Sherman
Affiliations:
Kite Pharma, Inc.,Santa Monica,United States
,
Arianne Perez
Affiliations:
Kite Pharma, Inc.,Santa Monica,United States
,
Allen Xue
Affiliations:
Kite Pharma, Inc.,Santa Monica,United States
,
Tatyana Feldman
Affiliations:
Lyphoma Division, John Theurer Cancer Center, Hackensack University Medical Center,Hackensack,United States
,
Jonathan W Friedberg
Affiliations:
University of Rochester School of Medicine,Rochester,United States
,
Mark J Roschewski
Affiliations:
Lymphoid Malignancy Branch, NCI, NIH,Bethesda,United States
,
Steven Feldman
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Lori McIntyre
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
,
Mary Ann Toomey
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
Steven A Rosenberg
Affiliations:
Surgery Branch, NCI, NIH,Bethesda,United States
EHA Learning Center. Goff S. Jun 12, 2016; 135286
Stephanie Goff
Stephanie Goff
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Abstract
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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
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