TCL1A Protein Identified as Predictor of Blinatumomab Response in Relapsed B-ALL

A study presented at the American Society of Hematology annual meeting identified TCL1A as a potential predictive biomarker for blinatumomab (Blincyto) response in relapsed pediatric B-cell acute lymphoblastic leukemia (B-ALL).

In this exclusive MedPage Today video, Andrew Hughes, MD, PhD, of the Children’s Hospital of Philadelphia, offers a summary of the groundbreaking findings on TCL1A and its role in improving treatment strategies for relapsed pediatric B-ALL.

Following is a transcript of his remarks:

My project is performing correlative biology studies that were embedded in the trial, ALL1331, which was a trial run by the Children’s Oncology Group, that compared blinatumomab to intensive multi-agent chemotherapy for relapsed pediatric B-ALL.

The trial was very successful. It was actually so successful that it was terminated early for loss of clinical equipoise. And now the blinatumomab-containing regimen is the standard of care in many centers for relapsed pediatric B-ALL.

So, it was very successful, but still not all patients responded to blinatumomab, and a significant proportion went on to experience a second relapse. So we’re looking at why those patients who didn’t respond, didn’t respond; why those patients who did respond, did respond. Because if we can get to a point where we can predict who will respond — or even better, understand the biology enough that we can turn non-responders into responders — we can improve outcomes even further.

What I presented at ASH is a preliminary finding that we’ve made, which we think is very exciting, which is that this protein called TCL1A, which has never been reported in a setting like this ever before, is significantly more abundant in responders compared to non-responders. Not only during the infusion, and it’s given for 28 days continuously, but actually before the infusion as well, specifically higher in responders in both the bone marrow and peripheral blood.

So we think that this protein, TCL1A, could be useful at least as a predictive biomarker of response to blinatumomab, but based on its biological function, could be involved in that actual response of the immune system to killing B-ALL cells in the setting of blinatumomab. It’s still early work and there’s a lot of work left to do to dissect this, the role of this protein further, but it’s a pretty good start.