ASH 2018: CAR.CD30 T-Cell Therapy in Relapsed or Refractory CD30-Positive Lymphomas
At the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition, Grover et al presented preliminary results from a clinical study of an investigational cellular immunotherapy for Hodgkin lymphoma and non-Hodgkin lymphoma expressing the CD30 protein marker (Abstract 681). Data from the phase Ib/II trial showed that the treatment was safe, and it generated responses when used after a regimen containing fludarabine and bendamustine, said researchers.
“Our results were definitely promising, especially given how many patients in the study had progressed on other treatments,” said Natalie Grover, MD, Assistant Professor in the University of North Carolina School of Medicine Division of Hematology/Oncology. “Hodgkin lymphoma is a generally curable disease, but there is a small percentage of patients who have…disease that doesn’t respond to therapy….[T]his could be a promising option for them.”
Study Methods
Researchers presented preliminary data for 24 patients. The majority of patients (16) had Hodgkin lymphoma. Prior to enrolling in the study, most patients had received more than seven treatments, including brentuximab vedotin (Adcetris), which can target the CD30 marker.
In the study, the researchers pretreated the patients with chemotherapy—a treatment method they called lymphodepletion—prior to an infusion of chimeric antigen receptor modified T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts).
Two dose levels were tested: 1×108 CAR-Ts/m2 (DL1) and 2×108 CAR-Ts/m2 (DL2).
Fourteen patients with evidence of disease prelymphodepletion were included in efficacy analysis. Of these 14, 6 patients had a complete response (43%, all in the bendamustine/fludarabine cohort), 1 had partial response (7%), 2 had stable disease (14%), and 5 had progressive disease (35%) at disease assessment. At a median follow-up of 138 days, the median progression-free survival was 129 days. The median progression-free survival for 3 patients who received bendamustine at DL1 was 55 days vs 172 days for the 9 patients who received bendamustine/fludarabine at DL2 (P = .039). Two patients remain in complete response at 1 year.
“The most important findings were that we identified a lymphodepletion regimen that can be used with these specific CAR T-cells, and make a difference in the outcome for these patients without significant toxicities associated with other cellular immunotherapies,” said the study’s senior author Barbara Savoldo, MD, PhD, Assistant Director of the UNC Lineberger Immunotherapy Program and Professor of Pediatrics in the Division of Hematology/Oncology at the UNC School of Medicine.
Researchers said their work will be ongoing to try to improve outcomes for the investigational treatment, including through another clinical trial that is designed to evaluate a mechanism for helping to recruit CAR T-cells to tumor sites.
The study was supported by the University Cancer Research Fund.
Disclosure: See the study authors’ full disclosures at ash.confex.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
