The study’s invited discussant, Ryan J. Sullivan, MD, Assistant Professor of Medicine, Harvard Medical School, and Assistant Professor in Hematology/Oncology at Massachusetts General Hospital, welcomed the positive results from the updated analysis of lifileucel in treatment-refractory melanoma.
“There have been limited clinical trial data in this population, and they generally involve an anti–PD-1 antibody plus an additional agent. The response rate in these studies has been 15% to 25%, and although that’s better than nothing—and some patients have durable responses—it’s still not good enough,” he said.
Ryan J. Sullivan, MD
Tumor-infiltrating lymphocytes as a treatment for melanoma was developed at the National Cancer Institute. It involves harvesting cells from a tumor, isolating the tumor-infiltrating lymphocytes, growing and expanding them, lymphodepleting the patient, infusing the T cells, and “chasing” this with a high dose of interleukin-2. In the past, this treatment has been available only at certain centers, with no commercial product available. This may change with lifileucel, which is “attempting to become that commercially available product,” noted Dr. Sullivan.
Recap of Safety and Efficacy
In the study, 66 patients underwent resection for the purpose of generating tumor-infiltrating lymphocytes. Dr. Sullivan learned from Dr. Sarnaik that the attrition rate was 18% for patients with tumors harvested, but in just 6% of cases was this due to a manufacturing failure.
“The safety of this treatment has been well described. Essentially, its toxicity is substantial, but it’s limited in time,” he said. Basically, the toxicity is related to lymphodepleting chemotherapy and the high-dose interleukin-2. Most patients recover completely, and there is very little in the way of long-term toxicity.”
Responses were in the mid-30% range, and the waterfall plot’s inflection point “was far beyond 50%,” said Dr. Sarnaik. “Of note, these responses tended to be durable, with the majority lasting more than 12 months. At a median follow-up of 18.7 months, the median duration of response had not been met.”
Addressing an Unmet Need
“Lifileucel is a commercial tumor-infiltrating lymphocyte product that allows for more widespread availability of this treatment modality. It showed remarkable response rates in a treatment-refractory population, and although it’s acutely toxic, there is a very low rate of long-term toxicity. Does this study address an unmet need? I would say, definitely, yes,” Dr. Sullivan concluded.
He added that although similar efficacy is observed in the study’s other cohorts, this may be a treatment modality “we are all going to need to learn how to give.”
DISCLOSURE: Dr. Sullivan reported financial relationships with ACI Clinical, Array Biopharm, Asana Biosciences, Merck, Novartis, Replimmune, Syndax, WorldCare Clinical, and Boehringer Ingelheim.
