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[georgejjl]

CD19 CAR-T cells combined with ibrutinib to induce complete remission in CLL.

Sub-category:
Chronic Lymphocytic Leukemia (CLL)

Category:
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Meeting:
2017 ASCO Annual Meeting

Abstract No:
7509

Poster Board Number:
Poster Discussion Session (Board #271)

Citation:
J Clin Oncol 35, 2017 (suppl; abstr 7509)

Author(s): Saar Gill, Noelle V. Frey, Elizabeth O. Hexner, Simon F. Lacey, Jan Joseph Melenhorst, John C. Byrd, Susan Metzger, Taylor Marcus, Whitney Gladney, Katherine Marcucci, Wei-Ting Hwang, Carl H. June, David L. Porter; University of Pennsylvania, Philadelphia, PA; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH

Abstract Disclosures

Abstract:
Background: Immunotherapy with anti-CD19 CART cells induces complete remission (CR) in the minority of patients with CLL, but where CRs occur they tend to be durable. Based on preclinical evidence of synergy, we combined anti-CD19 CAR T cells with ibrutinib to test the hypothesis that pre- and concurrent treatment would enhance the CR rate. Methods: This is a pilot trial of anti-CD19 CAR T cells in adults with CLL/SLL who were not in CR despite at least 6 months of ibrutinib. Pts must have failed at least 1 regimen before ibrutinib, unless they had del(17)(p13.1) or a TP53 mutation. T cells were lentivirally transduced to express a CAR comprising CD3z, 4-1BB, and humanized anti-CD19 scFv (CTL119). Pts were lymphodepleted 1 week before infusion. Ibrutinib was continued throughout the trial. Results: Manufacturing was successful in all pts. Ten pts (9M, 1F; ages 47-77; 0-12 regimens prior to ibrutinib) have been infused. All had abnormalities of TP53 or ATM and two pts had increasing BTK C481S clones. Median marrow CLL burden was 10% (range 10-50%). The median follow-up is 6 months (range 0.5-9). Cytokine release syndrome (CRS) developed in 9 pts; gr1 in 2, gr2 in 6 and gr3 in 1 pt. One pt developed gr4 tumor lysis syndrome. Treatment of CRS with the IL-6 receptor antagonist tocilizumab was not required. At 3 months, 8 evaluable pts had achieved an MRD-ve marrow CR (89%) by 9-color flow, and all remain in marrow CR at last F/U. There was modest residual splenomegaly in 3/5 patients, and adenopathy resolved in 4/6 subjects with progression in 1/6. MRD assessment by deep sequencing will be presented. Conclusions: We observed 89% MRD-ve marrow CR in pts with high-risk CLL using a well-tolerated combination of CART cells and ibrutinib. Longer follow-up will reveal the durability of these results and could support evaluation of a first-line combination approach in an attempt to obviate the need for chronic therapy. Clinical trial information: NCT02640209

Good luck and GOD bless,

George