[ Visit Client Website ]

Before you can access ASH's online program, you must agree to the following:
  • Abstracts submitted to the ASH Annual Meeting are considered embargoed from the time of submission.
  • The media, companies and institutions issuing press releases, and others are required to abide by the embargo policies governing the Society’s annual meeting. Read ASH’s embargo policy for more information.
-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

168 Effective Treatment Of Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma With Autologous T Cells Genetically-Engineered To Express An Anti-CD19 Chimeric Antigen ReceptorClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 801. Gene Therapy and Transfer: Progress in vector development and gene therapy of acquired diseases
Sunday, December 8, 2013: 6:15 PM
Riverside Rooms - R02-R03 (Ernest N. Morial Convention Center)

James N Kochenderfer, M.D.1, Mark E. Dudley, Ph.D.2*, Sadik H Kassim, Ph.D.3*, Robert O. Carpenter1*, James C Yang, MD3*, Giao Q Phan, MD4*, Marybeth S Hughes, MD3*, Richard M Sherry, MD3*, Steven Feldman, Ph.D.2*, David Spaner, MD, PhD5*, Debbie-Ann N. Nathan, RN2*, Kathleen E Morton, RN3*, Mary Ann Toomey, RN3* and Steven A. Rosenberg, M.D., Ph.D.2*

1Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD
2Surgery Branch, NCI, Bethesda, MD
3Surgery Branch, NCI, Bethesda
4Sugery Branch, NCI, Bethesda
5Sunybrook Odette Cancer Center, Toronto, ON, Canada

We have treated 20 patients and administered 23 total T-cell infusions on a clinical trial of autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19.  This is the largest reported clinical trial of anti-CD19-CAR T cells.  The first 9 CAR-T-cell treatments have been reported (Kochenderfer et al. Blood 2010 and Blood 2012).  This abstract communicates unreported results from 14 patients who received anti-CD19-CAR T cells produced with a new 10-day culture process.  These patients did not receive exogenous interleukin-2.  Of these 14 patients, 5 obtained complete remissions (CR), and 6 obtained partial remissions (PR), (see table). 

     The CAR used in this work is encoded by a gammaretrovirus and incorporates the variable regions of an anti-CD19 antibody, part of CD28, and part of CD3-zeta.  A mean of 70.5% of the infused T cells expressed the CAR, and the infused cells produced cytokines and degranulated in a CD19-specific manner.  Because prior chemotherapy has been shown to enhance the activity of adoptively-transferred T cells, patients received cyclophosphamide (total doses shown in table) plus fludarabine (25 mg/m2 daily for 5 days) before a single infusion of anti-CD19-CAR-transduced T cells.  

     This is the first report of successful treatment of chemotherapy-refractory primary mediastinal B-cell lymphoma (PMBCL) and diffuse large B-cell lymphoma not otherwise specified (DLBCL) with anti-CD19-CAR T cells.  All of the 8 treated patients with either PMBCL or DLBCL were chemotherapy-refractory, and 5 of these 8 patients obtained either a CR or PR on this trial.  We defined chemotherapy-refractory as progression or no response 1 month after the end of the most recent chemotherapy.  For example, Patient 2 had PMBCL that was refractory to 3 different chemotherapy regimens and that relapsed after radiation therapy.  Patient 2 obtained a CR after infusion of anti-CD19 CAR T cells and remains in CR 19 months post-infusion. 

     Blood B-cell depletion lasting more than 3 months occurred in 3 of 3 evaluable patients. Most patients were not evaluable for B-cell depletion due to B-cell depletion by prior treatments.  One patient died suddenly of unknown etiology 16 days after infusion of CAR T cells.  Acute toxicities including fever, hypotension, and delirium occurred after infusion of anti-CD19-CAR T cells.  The toxicities resolved in less than 3 weeks after the cell infusion and were temporally associated with elevated serum interleukin-6 and interferon gamma levels in most patients.  Peak blood levels of cells containing the CAR gene ranged from 2.3% to 66.5% of blood mononuclear cells.  These results demonstrate the feasibility of treating patients with chemotherapy-refractory B-cell malignancies by using autologous anti-CD19 CAR T cells.  The numerous remissions obtained should encourage further development of this approach.

Patient

Age/Gender

Malignancy

Number

of prior

therapies

Total cyclo-

phosphamide

dose

(mg/kg)

Number of

CAR+ T cells

infused

(X106/kg)

 

Response

(time

after cell

infusion in

months)

1

56/M

SMZL

4

120

5

PR (20+)

2

43/F

PMBCL

4

60

5

CR (19+)

3

61/M

CLL

2

60

4

CR (16+)

4

30/F

PMBCL

3

120

2.5

NE

5

63/M

CLL

4

120

2.5

CR (10+)

6

48/M

CLL

1

60

2.5

CR (7+)

7

42/M

DLBCL

5

60

2.5

CR (4+)

8

44/F

PMBCL

10

60

2.5

PR (6+)

9

38/M

PMBCL

3

120

2.5

SD (1)

10

57/F

Low-grade NHL

4

60

1

PR (4+)

11

58/F

DLBCL from CLL

13

60

1

PR (2)

12

60/F

DLBCL

3

60

1

SD (1+)

13

68/M

CLL

4

60

1

PR (2+)

14

43/M

DLBCL

2

60

1

PR (1+)

    SMZL, splenic marginal zone lymphoma; PMBCL, primary mediastinal B-cell lymphoma; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma not otherwise specified.  CR, complete remission; NE, not evaluable; PR, partial remission; SD, stable disease. (+) indicates an ongoing response.

Disclosures: Kochenderfer: Kite Pharma: Research funding is provided to the NCI by Kite Pharma for this trial. Other. Rosenberg: Kite Pharma: Research Funding.

<< Previous Abstract | Next Abstract

*signifies non-member of ASH