Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking

被引：219

作者：

Braig, Friederike ^{[1
]}

Brandt, Anna ^{[1
]}

Goebeler, Mariele ^{[2
]}

Tony, Hans-Peter ^{[3
]}

Kurze, Anna-Katharina ^{[4
,5
]}

Nollau, Peter ^{[4
,5
]}

Bumm, Thomas ^{[2
]}

Boettcher, Sebastian ^{[6
]}

Bargou, Ralf C. ^{[7
]}

Binder, Mascha ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Hubertus Wald Tumorzentrum, Dept Oncol & Hematol,Bone Marrow Transplantat Sec, Hamburg, Germany

[2] Univ Hosp Wurzburg, Dept Internal Med 2, Hematol Oncol, Wurzburg, Germany

[3] Univ Hosp Wurzburg, Rheumatol Clin Immunol, Wurzburg, Germany

[4] Childrens Canc Ctr, Res Inst, Hamburg, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[6] Univ Rostock, Div Med, Clin 3, Hematol Oncol & Palliat Med, Rostock, Germany

[7] Univ Hosp Wurzburg, Comprehens Canc Ctr Mainfranken, Wurzburg, Germany

来源：

BLOOD | 2017年 / 129卷 / 01期

关键词：

T-CELL THERAPY; MINIMAL RESIDUAL DISEASE; TERM-FOLLOW-UP; B-LINEAGE; ANTIBODY BLINATUMOMAB; TARGETED THERAPY; FREE SURVIVAL; REMISSIONS; PHASE-2;

D O I：

10.1182/blood-2016-05-718395

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

The CD19 antigen is a promising target for immunotherapy of acute lymphoblastic leukemia (ALL), but CD19(-) relapses remain a major challenge in about 10% to 20% of patients. Here, we analyzed 4 CD19(-) ALL relapses after treatment with the CD19/CD3 bispecific T-cell engager (BiTE) blinatumomab. Three were on-drug relapses, with the CD19(-) escape variant first detected after only 2 treatment courses. In 1 patient, the CD19(-) clone appeared as a late relapse 19 months after completion of blinatumomab treatment. All 4 cases showed a cellular phenotype identical to the primary diagnosis except for CD19 negativity. This argued strongly in favor of an isolated molecular event and against a common lymphoid CD19(-) progenitor cell or myeloid lineage shift driving resistance. A thorough molecular workup of 1 of the cases with early relapse confirmed this hypothesis by revealing a disrupted CD19 membrane export in the post-endoplasmic reticulum compartment as molecular basis for blinatumomab resistance.

引用

页码：100 / 104

页数：5

共 18 条

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