Novel CAR-T Cell Therapy Shows Promise in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

By Andrew John, /alert Contributor
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A novel CAR-T cell therapy showed promise in the treatment of patients with B-cell non-Hodgkin lymphoma whose disease did not respond to CD19 CAR-T therapy, according to findings from a phase 1 trial scheduled for presentation at the 2021 ASCO Annual Meeting.

“Relapse due to loss of the CD19 targeted epitope presents a therapeutic challenge of CD19 CAR-T therapy,” Aibin Liang, MD, PhD, of the Tongji University School of Medicine, Shanghai, and colleagues wrote in an abstract. “C-CAR066 is a novel second generation chimeric antigen receptor T (CAR-T) therapy targeting CD20 antigen.”

The researchers conducted a phase 1 study of C-CAR066, which was open to adults with relapsed or refractory diffuse large B-cell lymphoma, mantle cell lymphoma or follicular lymphoma. As of the end of January of 2021, seven patients with relapsed or refractory B-cell non-Hodgkin lymphoma (n = 6) or transformed follicular lymphoma (n =1) were enrolled. Only patients with an ECOG score of less than 2 were eligible. Patients had a median age of 51 years, and three (42.9%) were male. The patients had received a median of five prior therapies (range, 2-6).

Liang and colleagues administered a 3-day regimen of cyclophosphamide plus fludarabine, followed by a single infusion of the novel C-CAR066. Doses of the novel therapy ranged from 2 x 106 to 4.8x106 CAR-T cells/kg, and the researchers allowed bridging therapy.

Median follow-up was 7.8 months. The researchers reported that “the best overall response rate was 100%.” Five patients (71.4%) achieved a complete response. Patients had a median time of 1 month to response (range, 0.9-2.7), with a median of 2.7 months to complete response (range, 0.9-2.8).

All patients experienced cytokine release syndrome, 85.7% of whom were graded at 1 or 2. One patient experienced grade 4 CRS; however, this patient recovered after receiving corticosteroids and tocilizumab.

Three patients experienced disease progression by the time of the cutoff-date. The study did not reach median duration of response.

“These results show that C-CAR066 has a different mechanism of action compared to anti-CD-19 CAR-T therapy and could provide a solution to address the unmet medical need in B-NHL patients that have failed anti-CD19 CAR-T therapy,” Liang and colleagues wrote.

Disclosures: Liang reports no relevant financial disclosures. Please see the abstract for a complete list of all authors’ relevant financial disclosures.


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