Autologous CAR T-Cell Therapy Induces Durable Responses in Relapsed/Refractory Hodgkin Lymphoma

A high rate of durable complete responses (CRs) was observed with CD30-directed autologous chimeric antigen receptor (CAR) T-cell therapy as treatment of heavily pretreated patients with relapsed/refractory Hodgkin lymphoma in 2 independent phase 1/2 clinical trials, Tessa Therapeutics announced in a press release.¹

The results of these studies have been published in the Journal of Clinical Oncology, which also demonstrated a favorable safety profile with the autologous CD30 CAR T-cell therapy.

"These data are significant, as they demonstrate that CAR T-cell therapy may be a safe and effective treatment option for patients with Hodgkin lymphoma and potentially other lymphomas expressing the CD30 antigen," said Natalie Grover, MD, study co-first author, assistant professor in the Department of Medicine, University of North Carolina (UNC) and a UNC Lineberger member, in a statement.

Overall, 41 adult patients with relapsed/refractory Hodgkin lymphoma were enrolled to the studies and received CD30 CAR T-cell therapy following lymphodepletion with chemotherapy. Ninety-four percent of patients remained alive 1 year after treatment. Among the patients who achieved a CR, 61% had no evidence of recurrence 1 year later.²

None of the patients had experienced serious or life-threatening complications that have been associated with CD19-directed CAR T cells in clinical trials.

The most common toxicities observed in the trial were grade 3 or greater hematologic adverse events. Cytokine release syndrome, a toxicity commonly associated with CAR T cells, occurred in 10 patients, which was only grade 1 in all patients. No neurologic toxicities were observed.

The overall response rate was 72% in the 32 patients who had active disease and received fludarabine-based lymphodepletion, which included 19 patients (59%) who achieved a CR. After a median follow-up of 533 days, the 1-year progression-free survival rate was 36% (95% CI, 21%-51%). The 1-year overall survival rate was 94% (95% CI, 79%-99%).

"The highest dose treatment led to the complete disappearance of tumors in the majority of patients, and almost all subjects had clinical benefit. As such, we believe further study of this treatment approach is warranted," said Carlos Ramos, MD, study co-first author, professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, in a statement.¹

Investigators conducted the 2 parallel phase 1/2 clinical trials (NCT02690545 & NCT02917083) at 2 independent centers. To be included in either study, patients had to have relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma and a CD20-positive tumor. They also had to have a Karnofsky or Lansky score of > 60%, bilirubin 1.5 times or less than the upper limit of normal (ULN) and aspartate aminotransferase 3 times or less than the ULN.

Following lymphodepletion with either bendamustine (Bendeka) alone, bendamustine plus fludarabine, or cyclophosphamide and fludarabine, patients received the CD30 CAR T-cell therapy. The primary end point was safety.

Patients had received a median of 7 prior lines of therapy (range, 2-23), which included brentuximab vedotin (Adcetris), immune checkpoint inhibitors, and stem cell transplantation.

As treatment of patients with B-cell malignancies, CAR T cells have proven effective. These trials aimed to determine whether the same approach of CAR T cells, specific to CD30, could be used to treat patients with Hodgkin lymphoma as well.²

Overall, patients in this study were heavily pretreated and were able to achieve a high rate of durable responses with the CD30 CAR T-cell therapy. This research highlights the feasibility of extending these therapies beyond B-cell malignancies.

"We have been working with Baylor and the University of North Carolina to confirm these impressive results further in a Tessa-sponsored regulatory phase 2 trial, which we aim to initiate this year," stated Ivan D. Horak, MD, president of Research and Development at Tessa Therapeutics. "Longer term, we seek to explore the potential of this therapy beyond Hodgkin's lymphoma to CD30+ expressing Non-Hodgkin lymphomas, where there is a demonstrated unmet need."

UNC and Tessa will collaborate to further develop and commercialize the CD30 CAR T-cell therapy. The company is currently working on 2 innovative cellular therapies, this CD30 CAR T-cell therapy, and virus-specific T cells.

_References

_{1. Tessa Therapeutics Announces Results from Two Independent Phase 1/2 Trials of Autologous CD30 CAR-T Cell Therapy in Patients with Relapsed or Refractory Hodgkin Lymphoma. News Release. August 6, 2020. Accessed August 6, 2020. https://prn.to/2PvZQAI}

_{2. Ramos CA, Grover NS, Beaven AW, et al. Anti-CD30 car t-cell therapy in relapsed and refractory Hodgkin lymphoma. Journ of Clin Oncol. doi: 10.1200/JCO.20.01342}