ACUTE LYMPHOBLASTIC LEUKEMIA - THERAPY, EXCLUDING
`TRANSPLANTATION: POSTER II |
`NOVEMBER 19, 2010
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`B Cell Aplasia In a Patient with Relapsed B Cell Acute Lymphoblastic
`Leukemia Following Re-Induction and Consolidation with
`Autologous T Cells Genetically Targeted to the CD19 Antigen
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`Marco L Davila, MD, PhD,*,1 Clare Taylor, MSc,*,2 Xiuyan Wang, PhD,*,2
`Jolanta Stefanski,*,2 Malgorzata Olszewska,*,2 Shirley Bartido, PhD,*,2 Mark Frattini, MD,*,3
` Michel Sadelain, MD, PhD,4 Isabelle Rivière, PhD,*,2 Renier J. Brentjens, MD, PhD*,4
`1Department of Medicine, Division of Medical Oncology,
`Memorial Sloan-Kettering Cancer Center, New York, NY, USA,
`2Cell Therapy and Cell Engineering Facility, MPC Program,
`Memorial Sloan-Kettering Cancer Center, New York, NY, USA,
`3Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA,
`4Department of Medicine, Center of Cell Engineering and Molecular
`Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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`Blood (2010) 116 (21) : 3268.
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`http://doi.org/10.1182/blood.V116.21.3268.3268
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`Abstract
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`Abstract 3268
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`Despite high initial remission rates following induction chemotherapy, most adults with B cell acute
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`lymphoblastic leukemia (B-ALL) ultimately relapse and the overall prognosis is poor. In light of the overall
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`poor outcomes seen with currently available chemotherapy regimens as well as allogeneic stem cell
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`transplantation, novel and effective treatment approaches are needed for these patients. To this end,
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`we have developed a program utilizing a patient's own T cells genetically modified ex vivo to express
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`a chimeric antigen receptor (CAR), termed 19–28z, specific to the CD19 antigen expressed on normal
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`B cells as well as most B-ALL tumors. In preclinical studies, human T cells modified to express the 19–
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`28z CAR effectively eradicated systemic human B-ALL NALM-6 tumors in SCID-Beige mice. Based
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`on these findings we have recently opened a phase I clinical trial (IRB #09-114) wherein patients with
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`relapsed B-ALL are initially treated with re-induction chemotherapy followed by consolidation with high
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`dose cyclophosphamide (3gm/m2) and a subsequent infusion of autologous T cells genetically modified
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`Miltenyi Ex. 1047 Page 1
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`to express the 19–28z CAR. Herein, we report the initial findings of the first patient treated on this clinical
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`trial. This patient, a 67-year-old male, with B-ALL (normal cytogenetics), achieved a complete remission
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`following induction chemotherapy with mitoxantrone and high-dose cytarabine. The patient remained
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`in remission following treatment with vincristine (consolidation B) and cyclophosphamide (consolidation
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`C). However, he was noted to have relapsed disease following consolidation cycle D with cytarabine
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`and etoposide. At the time of relapse the patient was leukapheresed to obtain autologous T cells, and
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`subsequently achieved a second remission following re-induction with a modified PEG-asparaginase,
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`vincristine, and prednisone regimen. Upon recovery, the patient, as stipulated by the clinical trial, received
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`lymphodepleting consolidation with high dose cyclophosphamide followed, 2 and 3 days later, by a split
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`dose infusion of 3 × 106/kg autologous 19–28z+ T cells, the lowest planned T cell dose on this trial. Over
`the next 2 weeks, FACS and Q-PCR detected gene-modified T cells in the peripheral blood. Significantly,
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`over the next 5 weeks, despite recovery of neutrophils and T cells, the patient exhibited a persistent B cell
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`aplasia consistent with CD19-targeted cytotoxic activity of the infused autologous 19–28z+ T cells. The
`patient subsequently received an allogeneic stem cell transplant from a HLA-identical sibling effectively
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`abrogating further analysis of modified T cell function. Despite this limitation, we conclude that following
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`lymphodepleting chemotherapy, modified CD19-targeted T cells exhibit effective anti-CD19 cytotoxic
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`activity, as demonstrated by the persistent B cell aplasia, in the clinical setting. These findings support the
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`promise of this novel adoptive T cell therapy in patients with relapsed B-ALL.
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`Disclosures:
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`No relevant conflicts of interest to declare.
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`Author notes
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`* Asterisk with author names denotes non-ASH members.
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`© 2010 by the American Society of Hematology
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