CAR-T Safe, Active in Hodgkin Lymphoma – MedPage Today

A majority of patients with relapsed/refractory Hodgkin lymphoma responded to CD30-targeted chimeric antigen receptor (CAR) T-cell therapy, which caused no significant toxicity, a preliminary clinical study showed.

Overall, 23 of 37 (62%) evaluable patients had objective responses. The response rate increased to 72% when limited to 32 patients who received fludarabine, 19 of whom achieved complete responses.

The most common grade 3 adverse events were hematologic. No patient had grade >1 cytokine release syndrome (CRS), and no neurologic toxicity occurred, Barbara Savoldo, MD, PhD, of the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center in Chapel Hill, and co-authors from UNC and Baylor College of Medicine in Houston reported in the Journal of Clinical Oncology.

"This is particularly exciting because the majority of these patients had lymphomas that had not responded well to other new therapies," said Savoldo. "This treatment showed remarkable antitumor activity without significant toxicity, and we think it should be considered for patients in earlier stages of refractory/relapsing Hodgkin lymphoma."

The vast majority of patients with Hodgkin lymphoma can be cured with first-line therapy, but about 15% of patients have relapsed/refractory disease. The current standard of care for relapsed/refractory Hodgkin lymphoma is chemotherapy followed by autologous stem cell transplantation (SCT), but about half of patients relapse after SCT, Savoldo and co-authors noted.

CD30 is universally expressed by Hodgkin/Reed-Sternberg cells and has proven to be a safe target for novel therapies, such as brentuximab vedotin (Adcetris), which achieves sustained remissions in about a fourth of patients with relapsed/refractory Hodgkin lymphoma. Savoldo and colleagues sought to demonstrate that the same approach for using CAR T-cell therapy to treat B-cell malignancies -- targeting the CD19 antigen -- can be applied to treatment of Hodgkin lymphoma with anti-CD30 CAR T-cell therapy.

Clinical evaluation began with a phase I study with anti-CD30 therapy infused without lymphodepleting conditioning treatment. The therapy proved to be safe but had limited clinical activity.

Investigators continued clinical evaluation of the anti-CD30 therapy with lymphodepletion. A total of 41 patients with relapsed/refractory Hodgkin lymphoma received the genetically modified T cells. All patients had received at least two prior lines of therapy (and as many as 23) and a median of seven prior therapies.

Patients received one of three lymphodepleting regimens: cyclophosphamide-fludarabine, bendamustine alone, or bendamustine-fludarabine. A single infusion of anti-CD30 CAR T cells was administered 2 to 5 days after completion of lymphodepleting therapy. Patients who had stable disease or partial response after the infusion could receive a second infusion.

Of the 37 evaluable patients, 34 received fludarabine conditioning. Two of those patients had attained complete remission prior to CAR T-cell infusion and were not included in the efficacy analysis. The treatment led to objective responses in 23 of 32 (72%) patients, consisting of 19 complete responses and four partial responses. Three additional patients had stable disease.

The authors reported no dose-limiting toxicities associated with the CAR T-cell therapy. Ten patients developed grade 1 CRS, which resolved spontaneously in all cases without tocilizumab (Actemra) or corticosteroids. No patient developed grade >1 CRS.

The most commonly reported grade 3 adverse events were lymphopenia (100%), leukopenia (57%), nonpruritic maculopapular skin rash (48%), neutropenia (48%), and thrombocytopenia (26%).

Investigators are looking at biomarkers and clinical factors that might inform future use of the CD30-targeted therapy by helping to identify characteristics associated with response.

"We've started looking at the products made from the patients, the composition, so that we can anticipate what is the right composition of the product to give each patient," Savoldo told MedPage Today. "We're also looking at intrinsic factors in the tumor and in the tumor microenvironment to determine what other players in the immune system play a role."

The researchers are also exploring use of the CAR T-cell therapy in other CD30-associated diseases, especially poor-prognosis conditions, she added.

Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures

The study was supported by the National Cancer Institute, the Leukemia & Lymphoma Society, and UNC Oncology.

Savoldo disclosed relationships with Tessa Therapeutics, Cell Medica, Bluebird Bio, and Bellicum Pharmaceutical, as well as patent/royalty/intellectual property interests. First author Carlos A. Ramos disclosed relationships with Novartis and Tessa Therapeutics.

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CAR-T Safe, Active in Hodgkin Lymphoma - MedPage Today