The combination of tumor-infiltrating lymphocytes and chemotherapy showed a robust response rate and improvements in progression-free survival in a phase 1/2 study.
Combining autologous tumor-infiltrating lymphocytes (TIL) therapy and platinum-based chemotherapy shows potential as a novel treatment option for patients with epithelial ovarian cancer, according to a phase 1/2 study (NCT04072263) from the Leiden University Medical Center in Leiden, the Netherlands.1
As of the data cutoff point of April 2023, 14 completed treatment with a full TIL cycle and were evaluated for clinical and immunological response. A total of 3 patients treated with platinum-based chemotherapy and TIL infusion achieved a complete response (CR), 9 achieved a partial response, and 2 showed stable disease, resulting in an objective response rate of 86% and a 100% disease control rate (DCR) at 6 months.
One cohort of patients was treated with interferon-α (IFNa) added to TIL and chemotherapy; however, this combination demonstrated toxicity, and 2 of 3 patients developed grade 3 thrombocytopenia and grade 4 neutropenia. Patients treated without IFNa did not experience any toxicities other than those expected from platinum-based chemotherapy alone.
“Our results show that it is feasible to obtain TIL for treatment and that it is safe to treat patient with TIL during platinum-based chemotherapy, when given without additional IFNa. The platinum-based chemotherapy induced reduction of myeloid cells is maximal at 1-2 weeks after the second chemotherapy and, therefore, considered the optimal timing for TIL infusions,” study authors wrote.1
Additionally, the chemotherapy/TIL combination did not appear to affect the levels of T-cell-supportive circulating cytokines IL-7, IL-15, and IL-21.
The median platinum-free interval (PtFI) after treatment was 6.5 months (range, 2-35). The median progression-free survival (PFS) was 10.7 months (range, 6-39+), and the median platinum-free survival was 6.5 months. The median probably of overall survival was 34.7 months, according to Kaplan-Meier analysis performed at the data cutoff of April 2023.
One patient had an ongoing PFS that increased fivefold after chemotherapy and TIL. Another patient had an exceptionally long, ongoing CR that was observed with a concurrent sustained alleviation of immune suppression.
Absolute numbers of monocytes and neutrophils were reduced, but there was little effect to absolute lymphocyte counts. Monocyte counts generally returned to baseline within 2 weeks after the 3rd chemotherapy cycle, but neutrophils stayed decreased. Of note, the greatest reduction in monocyte and neutrophil numbers was observed in the patient with the most durable PtFI.
Patients were enrolled in the study between November 2018 and March 2021. The median patient age was 61 years (range, 29-77). All but 1 patient had histologically confirmed high-grade serious ovarian carcinoma. All patients had an ECOG performance status of 0-1, recurrent, platinum-sensitive disease, and a PtFI between 6-12 months.
The primary end point of the trial was incidence of adverse events. Secondary end points included clinical response, DCR, PFS, and overall survival.2