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Following Progression on CAR T-Cell Therapy, B-Cell Lymphoma Treatment Options Needed

Danielle Ternyila
Published: Tuesday, Feb 12, 2019

Victor A. Chow, MD
Victor A. Chow, MD
Patients with large B-cell lymphoma who experience disease progression following CD19-targeted chimeric antigen receptor (CAR) T-cell therapy have poor long-term outcomes. Therefore, effective therapeutic strategies need to be identified for this patient population, explained Victor A. Chow, MD.

In a retrospective study that was presented during the 2018 ASH Annual Meeting, researchers at Fred Hutchinson Cancer Research Center evaluated the outcomes of 55 patients with various B-cell lymphomas who progressed on CD19-specific CAR T-cell therapy. Results showed that those with large B-cell lymphomas who show evidence for early progressive disease after receiving this type of treatment have poor outcomes. This high-risk group of patients represents an unmet need in identifying therapy options following progression, said Chow, a senior hematology/oncology fellow at the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance.

“We need to be thinking strategically about how to look at the next subsequent treatment for them so hopefully patients will get a sense that once their CAR T cell fails them, we’re not just giving up on them. We’re still trying to think about other options to help prolong or get them back into remission,” Chow said.

In an interview with OncLive, Chow, who was the lead author of this retrospective study, highlighted the trial, its findings, and the next steps in understanding how to treat patients who progress after CAR T-cell therapy.

OncLive: Could you provide background to this study, which looked at disease progression after CD19-targeted CAR T-cell therapy?

Chow: This study really came about [because] as lymphoma specialists, we see a lot of patients, unfortunately, with relapsed/refractory large B-cell lymphomas after CAR T-cell therapies. In the last year, [there] has been a huge change and dramatic shift in terms of treatment options for patients with not many very good options. We have been seeing a lot of good outcomes from CAR T-cell therapy, but unfortunately, there is still a good proportion of patients who still relapse disease following CD19-specific CAR T-cell therapy.

Our clinical question is when they come back to see us in clinic, what do we do? How do we treat them? What is the standard of care? What are their options? As amazing and good the hype is, [we are still] understanding how this therapy should be figured into the treatment algorithm when they’re back in clinic with us. One lingering question that remains is, “What do we do now?” That was behind why we wanted to look at this study.

How was this study designed?

This was a retrospective study, and we looked at essentially all of the patients at our center that got any CAR T-cell product that was CD19-specific for diffuse large B-cell lymphoma, transformed follicular lymphoma, primary mediastinal large B-cell lymphoma, and high-grade B-cell lymphoma. We specifically looked for individuals who had evidence for progressive disease immediately after their CAR T-cell therapy. Generally, folks will get staged again in 28 or 30 days or so. We also looked at individuals who had late progression of disease, meaning they had evidence of complete response (CR), partial response (PR), or stable disease initially, but later on had evidence of progression of disease. We identified these individuals and looked at their outcomes.

What were the findings?

When we looked at all of our patients who had evidence for progressive disease, we identified 55 patients. Their overall survival (OS) was a median of a little over 5 months. This is taking into account both early and late progression, which is not a great outcome certainly. We can be doing more to help our patients, hopefully improving CR rates and also decreasing progressive disease rates.


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Community Practice Connections™: 2nd Annual International Congress on Immunotherapies in Cancer™: Focus on Practice-Changing ApplicationFeb 28, 20192.0
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