Transcriptome Analysis Identifies a Myeloid-Like Signature in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Poor Response to CD19 Chimeric Antigen Receptor T Cell Therapy.

What was studied

This study looked at people with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia. They were treated with CD19 CAR-T cell therapy. Responses to this therapy differ from person to person. The team asked if bone marrow gene activity before treatment could explain poor response. It used a single-arm clinical trial. The people were split by response: 8 were good responders and 7 were poor responders. The team also built an exploratory gene score.

What they found

Poor responders showed a myeloid-like signature. Myeloid-related genes were more active in them. The team checked 7 of these genes in other patient groups and in cell lines. They also checked one patient at single-cell level. Some genes were made by the leukemia cells themselves. Others came mainly from monocytes and macrophages. A separate gene score split the groups in the first cohort. Its AUC was 1.00. Corrected and outside estimates were about 0.57-0.59. In the outside cohort, the AUC was 0.592.

What it means for patients

The authors say the pre-treatment gene profile showed a myeloid-like signature in poor responders. They say it warrants further study as a candidate marker of treatment outcome.

Why it is not certain yet

Only a small group was in the trial. There was no comparison group. The gene score did far worse outside the first cohort. The range around 0.592 was wide, from 0.356 to 0.828. The authors call the score exploratory.

Source

Transcriptome Analysis Identifies a Myeloid-Like Signature in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Poor Response to CD19 Chimeric Antigen Receptor T Cell Therapy.

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