21st ISCT Annual Meeting S13

have observed serious adverse events (SAEs) and toxicities attributable to the
administration of CAR T cells, the most clinically significant being cytokine
release syndrome (CRS). In addition, a recent case report described a patient
who developed an anaphylaxis reaction to CAR T cells, ultimately attributed to
receipt of multiple doses of cells. As there are a number of ongoing clinical
trials at our institution utilizing CAR T cells to treat various hematologic and
solid malignancies and several patients have received multiple doses, we per-
formed a retrospective review to assess whether early or late infusion toxicities
were observed with subsequent infusions. We identified 45 of over 200 patients
who received more than one dose of CAR T cells between January 2009 and
December 2014. We assessed patient characteristics including type of malig-
nancy, disease status at the time of subsequent infusions, cell product (autol-
ogous vs. allogeneic), presence or absence of prior lymphodepletion, number of
infusions, dosing schedule, and the relationship to development of CRS. Each
characteristic was examined for any correlation to developing a SAE. Our re-
sults indicate that at our institution, repeated CAR T cell infusions are well
tolerated, with the majority of grade 3-4 adverse events being hematologic and
electrolyte abnormalities. Furthermore, the majority of SAEs reported after
repeated CAR T cell infusions were attributed as unrelated to the infusion
itself. However, further evaluation of a larger cohort is necessary to determine
whether an association between the timing of repeated infusions and CRS and
other SAEs exists. These findings and our continued evaluation of patients
receiving multiple infusions will help us to ensure the safety of administering
multiple doses of CAR T cells in the future.
22
CHIMERIC ANTIGEN RECEPTOR MODIFIED T CELLS
DIRECTED AGAINST CD19 (CTL019) INDUCE CLINICAL
RESPONSES IN PATIENTS WITH RELAPSED OR REFRACTORY
CD19+ LYMPHOMAS
B Levine1, J Svoboda2, SD Nasta2, D Porter2, E Chong2, S Lacey3,
Y Mahnke1, J Melenhorst1, A Chew3, G Shah4, J Hasskar5, M Wasik1,
D Landsburg2, A Mato2, A Garfall2, N Frey2, P Shaw6, K Marcucci3, J Shea3,
H McConville3, N Manvar1, M O’Rourke1, A Lamontagne1, A Bersenev1,
Z Zheng1, S Schuster2, C June3
1 months (p¼0.003, 0.001 and 0.001 respectively). At 12 months, 85% of group IA
Department of Pathology and Laboratory Medicine, Abramson Cancer
Center, University of Pennsylvania, Philadelphia, Pennsylvania, United
States, 2Lymphoma Program, Abramson Cancer Center, University of
Pennsylvania, Philadelphia, Pennsylvania, United States, 3Translational
Research Program, Abramson Cancer Center, University of Pennsylvania,
Philadelphia, Pennsylvania, United States, 4Novartis, East Hanover, New
Jersey, United States, 5Novartis, Basel, Switzerland, 6Biostatics and
Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, United
States
23
COMBINED LOCAL MELANOCYTES AND SYSTEMIC
MESENCHYMAL STEM CELL INJECTION IN VITILIGO
TREATMENT
H Gabr, WA Elkheir
Clinical Pathology, Cairo University, Cairo, Egypt
Background: Vitiligo is a cosmetically disfiguring acquired depigmenting
disorder caused by the loss of functional melanocytes. Autologous melanocyte
transplantation is a new effective treatment for stable vitiligo. Melanocyte
destruction is immune-mediated.
Mesenchymal stem cells (MSCs) have Immunomodulatory and immuno-
suppressive properties. MSCs will prevent damage to melanocytes and reduce
disease progession.
Study Objective: to examine the effectiveness and tolerability of systemic MSCs
in combination with local melanocyte application in treatment of vitiligo.
Study Design: A randomized, double-blind, placebo-controlled pilot study
with follow-up range from 3 to 12 months.
Patients and Methods: 50 vitiligo patients were recruited, divided into:
Group I Stable vitiligo
Group II Unstable vitiligo
Patients received:
- Group IA: cellular suspension (melanocyte + hyaluronic acid+MSC cells).
- Group IB: placebo (melanocyte medium + hyaluronic acid).
- Group IIA: local treatment, intravenous MSCs.
- Group IIB: local treatment, intravenous normal saline placebo.
Cellular suspension was applied after epidermal ablation and the lesion
covered with sterile dressing for 3-7 days.
Outcome Evaluation:
1. Percentage of area of repigmentation objectively assessed at 0, 3, 6, and 12
months after treatment and analyzed using a digital image analysis software.
2. Repigmentation pattern.
3. Scoring for stability using vitiligo disease activity score.
Results and Conclusions: There was statistically significant increase in
repigmented area in treated groups compared to placebo groups at 3, 6 and 12
patients showed repigmentation: 10% peripheral , 10% follicular and 65% mixed
repigmentation. In Group IIA, repigmentation was seen in lesions which were
not treated locally.
These results document the synergistic effect of systemic MSC and local
melanocyte application in treatment of unstable vitiligo.
Comparison between patient groups IA, IB and control as regards
the area of repigmentation at 0 day and after 3,6,12 months.6

Autologous T cells genetically modified to express a chimeric antigen receptor

Area of Area of Area of
consisting of an anti-CD19 antibody domain with CD3z and 4-1BB signaling Area of pigmentation pigmentation pigmentation
domains (CTL019 cells) can mediate potent anti-tumor effects in relapsed/ pigmentation after 3 after 6 after 12
refractory chronic or acute lymphoblastic leukemias. We report a phase IIa at 0 day months months months
clinical trial evaluating safety and efficacy of CTL019 cells in relapsed/re-
fractory CD19+ non-Hodgkin lymphomas (NHL). 30 evaluable patients (pts) Group 27.4018.79 35.0021.88 45.2526.18 52.2528.84
are planned, including pts with follicular lymphoma (FL), diffuse large B cell IA a A a a
lymphoma (DLBCL), and mantle cell lymphoma. Eligible pts have CD19+ Group 21.5016.84 26.0018.07 30.0019.15 33.0020.98
NHL with no available curative treatment options, limited prognosis of several IB a ab ab b
months to <2 years anticipated survival, and responsive or stable disease with Control 17.5013.18 17.5013.18 20.0014.72 22.5015.50
most recent therapy. One to 4 days after lymphodepleting chemotherapy, pts a B b b
receive a single dose of CTL019 cells. Peripheral blood and marrow samples
F ratio 1.203 2.879 4.658 5.530
are collected for analysis after T cell infusion. To date, 26 pts have enrolled.
The median number of prior therapies is 4 (range: 1-8), and number of pts with
P value 0.312 0.069 0.016 0.008
prior ASCT is 9 (35%). Six pts were removed before therapy due to progressive NS NS S S
disease, refusal to proceed, or inadequate T cell collection/expansion. 19 pts
have received CTL019 T cell infusions. Sixteen pts are evaluable for response
(DLBCL 11; FL 5). Overall response rate at >3 months is 63% with 8 com-
plete responses (DLBCL 4; FL 4) and 2 partial responses (DLBCL 1; FL 1); 6 24
pts with DLBCL had progressive disease before or at initial response assess- FUSOKINE GIFT4 TRIGGERS NOVEL B CELL FUNCTION ON
ment. 10 of the first 16 evaluable pts responded to therapy. These early results HEMATOPOIETIC STEM CELLS
demonstrate CTL019 cells can be prepared from previously treated pts with J Deng1, A Pennati1, S Yuan1, E Waller1, S Lonial1, K Roy2, J Galipeau1
1
active NHL, and can induce complete responses in pts with advanced, relapsed Hematology and Medical Oncology, Emory University Winship Cancer
or refractory DLBCL and FL. Longer follow up will define toxicities, dura- Institute, Atlanta, Georgia, United States, 2The Wallace H. Coulter
bility of response, and clinical benefit, and guide further development of this Department of Biomedical Engineering, Georgia Institute of Technology,
promising new therapeutic approach. Atlanta, Georgia, United States