CAR T therapy being explored in Hodgkin lymphoma


Photo courtesy of NCCN

Attendees at the NCCN 13th hematology congress

New York—Although the data set is small and not yet mature, chimeric antigen receptor (CAR) T-cell therapy appears to be a promising approach for Hodgkin lymphoma, according to Philippe Armand, MD, PhD, of Dana-Farber/Brigham and Women’s Cancer Center and the Massachusetts General Hospital Cancer Center.

While based on a handful of patients, the data do suggest this approach may play a role either by targeting CD30 or Epstein Barr virus (EBV), Dr. Armand said in a presentation at the NCCN 13th Annual Congress: Hematologic Malignancies.

“Most importantly perhaps, like it's experience outside of Hodgkin lymphoma, it may really have curative potential, based on the long CR rates that have been already exhibited,” he told attendees at the NCCN conference.

Much of the published clinical experience to date is with CD30-directed CAR Ts, Dr. Armand said, noting that in Hodgkin lymphoma, results so far show promise for this particular approach.

In a recent phase 1 dose escalation study, 9 patients with relapsed/refractory Hodgkin lymphoma or anaplastic large-cell lymphoma (ALCL) received infusions of autologous T cells modified to express CD30-specific CAR T cells encoding the CD28 costimulatory domain, with no conditioning regimen.

Out of 7 relapsed Hodgkin patients, one had a complete response (CR) lasting beyond 2.5 years following a second infusion. Another had a CR persisting almost 2 years and 3 had transient stable disease.

One of the 2 ALCL patients had a CR lasting 9 months after a fourth infusion. No toxicities attributable to the therapy were seen, according to investigators.

The CD30 CAR T cells are being evaluated with a conditioning regimen in the phase 1 RELY-30 trial. According to Dr. Armand, preliminary results presented at the EBMT 2018 meeting showed better expansion of CAR T cells and responses in 3 out of 5 patients, including 2 CRs.

A CD30-directed CAR T-cell therapy with a 4-1bb costimulatory domain has also been tested in a small group of Hodgkin patients with a response rate of 35%, including some CRs. Response rates were lower in patients with extranodal involvement, although that needs to be validated with further study, according to Dr. Armand.

A considerable amount of active research is ongoing in China, Dr. Armand said, while a phase 1 study of T cells expressing a fully human anti-CD30 CAR is being evaluated in the United States in CD30-expressing lymphomas, he added.

Among non-CD30-targeted products, a CD19 CAR-T approach has been tried in Hodgkin lymphoma, though preliminary results suggest only transient activity.

An interesting approach has been the targeting of EBV, Dr. Armand noted. Recently reported results showed that two doses of T cells with specificity for EBV-derived tumor antigens induced clinical responses in patients with EBV-positive Hodgkin lymphoma.

The cells were engineered to express dominant-negative TGF-β receptor type 2 (DNRII).

“We know that TGF-β provides a strong immunosuppressant signal in the tumor microenvironment,” Dr. Armand said, noting that some of the responses in the 7 evaluable patients lasted 4 years or more.

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