Lisocabtagene maraleucel, a CD19-directed 4-1BB CAR T-cell product, produced durable responses in patients with heavily pretreated relapsed-refractory diffuse large B cell lymphoma (R/R DLBCL) and appears to have manageable acute toxicities, investigators of the TRANSCEND NHL 001 trial (ClinicalTrials.gov identifier: NCT02631044) have found. Results of the study (abstract 7505) were reported at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
“Our update report includes 102 evaluable patients in the entire study, and 73 patients with relapsed/refractory DLBCL who represent patients being accrued in the pivotal cohort,” said study presenter Jeremy S. Abramson, MD, Clinical Director of the Lymphoma Program at Massachusetts General Hospital Cancer Center, Boston, Massachusetts. “Our response rate among all subjects was 75%, with complete responses in 55%. We also see evidence of a dose-response relationship between treatment arms.”
Dr. Abramason presented the updated safety and long-term clinical outcomes (6-month and 12-month) data resulting from an evaluation of lisocabtagene maraleucel in R/R aggressive NHL. The study included patients with R/R DLBCL, primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma grade 3B (FL3B), and mantle cell lymphoma (MCL); all patients had adequate organ function. Treatments included lymphodepletion with fludarabine and cyclophosphamide, followed by lisocabtagene maraleucel. The team investigated multiple dose levels and administration schedules for the therapies studied.
The researchers opted for a dose of 108 CAR T cells (dose level 2) for the current investigation. The primary objective of this study was to assess safety, pharmacokinetics, and antitumor response. “Among relapsed/refractory DLBCL and transformed follicular lymphoma patients treated in dose level 2, the best overall and complete response rates were 78% and 62%, respectively, and 49% of patients were in ongoing response at 6 months,” Dr. Abramason told Cancer Network.
He said durable responses were seen in all high-risk subgroups, including primary refractory disease and double hit lymphomas. “Dose level 2 has been taken forward in relapsed/refractory DLBCL and transformed follicular lymphoma in the pivotal phase of the trial. The high rates of response and durability are encouraging in this very high risk patient population,” said Dr. Abramason.
Among 102 evaluable patients, the researchers observed any-grade cytokine release syndrome (CRS) in 39% of patients. However, Dr. Abramson noted that this was a low-grade adverse event in nearly all patients, with only a single patient experiencing severe CRS. Neurotoxicity was observed in 23% of the patients, and it was severe in 13%. He said all of the toxicities were virtually always reversible, and there were no deaths from CRS or neurotoxicity. “These data demonstrate remarkable efficacy and safety of this CAR T-cell product, which is uniquely characterized by a defined cell composition which results in a precise dose of CD8 and CD4 CAR+ T cell administered to each patient,” said Dr. Abramson.