Novel CAR T-Cell Therapy Shows Promise in Advanced Hodgkin Lymphoma

Use of a novel anti-CD30 CAR T-cell therapy following treatment with fludarabine-based lymphodepletion induced a high rate of durable responses in patients with heavily pretreated relapsed or refractory Hodgkin lymphoma, according to data published in Journal of Clinical Oncology.

Results from the parallel phase 1 and phase 2 studies also demonstrated that the CAR T-cell therapy was safe and did not produce any serious or severe side effects.

Researchers from the UNC Lineberger Comprehensive Cancer Center and Baylor College of Medicine administered anti-CD30 CAR T cells to 41 patients with relapsed or refractory Hodgkin lymphoma. All patients underwent lymphodepletion with bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine prior to the anti-CD30 CAR T-cell therapy.

Measuring safety was the primary goal of the two parallel studies.

The overall response rate, or the percentage of partial or complete responses to therapy, among 37 evaluable patients was 62%. Thirty-four of the patients received fludarabine-based lymphodepletion – 17 of which received it with bendamustine, and the other half received it with cyclophosphamide. Two of these patients were considered to be complete response at infusion and maintained the response, so they were not included in final analysis.

The overall response rate among the remaining patients was 72%, with 59% of patients achieving a complete response. After a median follow-up of 533 days, researchers identified the one-year progression free survival rate to be 36% and the one-year overall survival rate to be 94%.

“This is particularly exciting because the majority of these patients had lymphomas that had not responded well to other powerful new therapies,” said senior study author Dr. Barbara Savoldo, professor in the Department of Microbiology and Immunology at the UNC School of Medicine, in a press release.

Patients within the study had received a median of seven previous lines of therapy that included checkpoint inhibitors and autologous or allogeneic stem cell therapies, therapies known to be powerful but also tend to come with a host of side effects.

However, treatment with the anti-CD30 CART cells demonstrated a favorable safety profile. Although 10 patients developed cytokine release syndrome, all cases were considered minor.

Patients who received fludarabine-containing lymphodepletion were the only participants in the study to have a response to the anti-CD30 CAR T-cell therapy.

“Although CD30 CAR T (cells) showed modest activity in (Hodgkin lymphoma) when infused without lymphodepletion, robust clinical responses were achieved when these cells were infused in hosts lymphodepleted with fludarabine-containing regimens,” the authors wrote.

“The activity of this new therapy is quite remarkable and while we need to confirm these findings in a larger study, this treatment potentially offers a new approach for patients who currently have very limited options to treat their cancer,” said Dr. Jonathan Serody, director of the bone marrow transplant and cellular therapy program at UNC Lineberger Comprehensive Cancer Center, in the release. “Additionally, unlike other CAR T-cell therapies, clinical success was not associated with significant complications from therapy. This means this treatment should be available to patients in a clinic setting and would not require patients to be hospitalized, which is critical in our current environment.”