Tumor infiltrating lymphocyte therapy feasible for metastatic NSCLC
medwireNews: Patients with metastatic non-small-cell lung cancer (NSCLC) may respond to adoptive cell therapy using tumor infiltrating lymphocytes (TILs), suggest results from a small phase 1 trial.
Presenting the data at the 2020 AACR Virtual Annual Meeting I, Ben Creelan (H Lee Moffitt Cancer Center, Tampa, Florida, USA) explained that TIL adoptive cell therapy has previously been used in the metastatic melanoma setting with durable complete responses in 10–15% of patients. The researchers therefore hypothesized that NSCLC patients “may also have durable remission” with the combination of TIL and anti-PD-1 therapy.
And indeed, the discussant Gal Markel (Sheba Medical Center, Ramat-Gan, Israel) described the study as “a very good proof-of-concept of clinical activity of TIL therapy” in advanced lung cancer patients.
In all, 20 patients with no prior exposure to PD-1 axis inhibitors were enrolled in the trial and had their TILs harvested from a resected metastatic lesion before receiving nivolumab 240 mg every 2 weeks for a total of four doses.
Sixteen patients displayed evidence of progression on nivolumab and underwent lymphodepletion with two doses of cyclophosphamide 60 mg/kg and five doses of fludarabine 25 mg/m2 in the week prior to receiving a single infusion of the expanded autologous TILs at a dose of 20–100 billion CD3+ cells, depending on growth.
Interleukin (IL)-2 was then given for 6 days after the TIL infusion, at an initial dose of 18.0 miU/m2 over 6, 12, and 24 hours on days 1, 2, and 3, respectively, followed by 4.5 miU/m2 over three 24-hour periods, after which patients received maintenance nivolumab 480 mg every 4 weeks, from day 29 for up to a year.
Creelan described the “diverse spectrum of responses” among the 12 patients with evaluable post-TIL data, which included two complete responses, one confirmed partial response (PR), one unconfirmed ongoing PR, and two unconfirmed PRs in patients who subsequently progressed with new lesions. The remaining six patients all had progressive or stable disease. This translated to an objective response rate of 25%.
Markel said it was “phenomenal” that TIL therapy elicited responses in the three patients who had progressed on previous lines of therapy and had low PD-L1 levels and tumor mutational burden (TMB) and were thus “hardly expected to respond to nivolumab.”
However, he pointed out that the other three responders had been treatment-naïve, with one having high PD-L1 levels and another high TMB. The discussant therefore emphasized that “after being exposed to only four doses of nivolumab […] it may be a bit hard to call these patients as primary failures.”
Creelan noted that the toxicities were “manageable,” with the most common adverse events of grade 3–4 being decreased lymphocyte and white blood cell counts, anemia, decreased neutrophil and platelet counts, and hypophosphatemia.
“Almost all adverse events occurred early and largely had resolved by 2 weeks,” highlighted Creelan, but there were two deaths, one of which was attributed to a stroke 23 days after receiving the TIL infusion and was partially attributed to the IL-2 treatment.
In conclusion, Creelan described the need to optimize TIL therapy in this setting “so that we can increase the response rate for more patients,” and he stressed that “finding ways to make it faster to produce, and fewer adverse events,” would make it a more accessible option.
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