Benefits of CD30 CAR-T Therapy for Multiply Relapsed Enteropathy-Associated T-Cell Lymphoma

Chimeric antigen receptor T-cell (CAR-T) therapy targeting the CD30 molecule promoted a durable remission in a 69-year-old man with multiply relapsed enteropathy-associated T-cell lymphoma after previous allogeneic stem cell transplantation. Clinicians described the case in a report published in Blood Advances.

“To our knowledge, this is the first case of enteropathy-associated T-cell lymphoma treated with CAR T-cell therapy,” wrote the authors, from the University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, and the Levine Cancer Institute in Charlotte, North Carolina. “In this patient, who had not achieved a durable response with six previous lines of therapy, including brentuximab vedotin, allo-stem cell transplantation, and multiple donor lymphocyte infusions, we are encouraged by both the depth and duration of response after CD30 CAR T-cell therapy.” 

The patient had celiac disease, which had been well-controlled for 9 years through a gluten-free diet. When he developed abdominal pain and nausea, he underwent endoscopy and biopsy, which showed CD30-positive enteropathy-associated T-cell lymphoma in the small bowel. After several lines of treatment, response, and relapse, the patient was referred to the University of North Carolina for CD30-targeted CAR-T therapy. 

Treatment with lymphodepleting chemotherapy and CD30 CAR T-cells was well tolerated by the patient, according to the report. Although pretreatment scans showed involvement of bilateral cervical, supraclavicular, and mediastinal nodes, as well as a single mesenteric node, 6 weeks after CD30 CAR-T therapy all locations had completely resolved.  

Continued remission was confirmed via routine imaging at 24 months—and more than 30 months after treatment, the patient remains well on follow-up physical exams, the authors reported.

“Well-designed clinical trials are needed to expand our understanding of and overcome obstacles when using CD30 CAR T-cells in T-cell lymphoma,” the authors advised. “The remarkable response observed in this patient should be confirmed in a larger phase 2 trial.” 

“To this end,” they added, “the University of North Carolina is currently enrolling patients with relapsed/refractory CD30⁺ peripheral T-cell lymphoma in a phase 2 trial that uses two sequential CD30 CAR T-cell infusions at the recommended phase 2 dose of 2 × 10⁸ CAR T-cells per m² (NCT04083495).” 

—Jolynn Tumolo 

Reference

Voorhees TJ, Ghosh N, Grover N, et al. Long-term remission in multiply relapsed enteropathy-associated T-cell lymphoma following CD30 CAR T-cell therapy. Blood Adv. 2020;4(23):5925-5928. doi:10.1182/bloodadvances.2020003218