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Maria J. Disselhorst
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-32 - Ki67+ PD-1+ Central Memory CD8 T-Cell Frequencies Predict Response Upon Nivolumab+Ipilimumab in Malignant Pleural Mesothelioma (ID 2270)
09:45 - 18:00 | Author(s): Maria J. Disselhorst
- Abstract
Background
New treatment options for malignant pleural mesothelioma (MPM) are urgently needed, as the only standard treatment, chemotherapy, has only modest activity in the majority of the patients. Recent clinical trials with checkpoint inhibitors have shown promising results in MPM patients who progressed after first line platinum-based chemotherapy. We reported on 2 phase II clinical trials which assessed nivolumab (aPD-1) monotherapy (NIVOMES) and the combination of nivolumab + ipilimumab (INITIATE). At the 12-week time point, the disease control was 47% for nivolumab and 68% for the combination. Here we report on differences in T cell subsets present in the peripheral blood at baseline and during treatment in both trials.
Method
Peripheral blood of 31 MPM patients enrolled in NIVOMES and 38 MPM patients enrolled in INITIATE was collected at baseline and 6-weeks after start of treatment. T-cell subsets frequencies and the expression of Ki67 and PD-1 on these subsets were determined by flow cytometry.
Result
An increased proportion of proliferating Ki67+ T-cells was found after 6-weeks of combination treatment with nivolumab/ipilimumab, which was not observed 6-weeks after treatment with nivolumab monotherapy. Increased proliferation was particularly observed in the effector memory (EM) and central memory (CM) CD4+ T-cells and EM CD8+ T-cells. Additionally, patients with a clinical response on combination therapy had a significantly higher frequency of PD-1+ Ki67+ CM CD8+ T-cells and effector memory re-expressing RA (EMRA) CD8+ T-cells compared to non-responders at baseline. These differences were not seen in patients that responded to nivolumab monotherapy. No alterations in the frequencies of either activated or naïve regulatory T cells (Tregs) were found in both treatment groups comparing baseline to 6 weeks.
Conclusion
Our results indicate that specifically in patients that respond to combination therapy the frequency of PD-1+Ki67+ CM CD8 T-cells at baseline was significantly increased, whereas combination therapy in both responding and non-responding patients increased proliferation of memory T-cell subsets. This indicates that addition of ipilimumab to nivolumab treatment reinvigorates T-cell responses in general, whereas responding patients present with elevated immune activation already at baseline. In conclusion, we were able to select MPM patients that are most likely to benefit from combination therapy of nivolumab and ipilimumab at baseline.
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WS02 - Mesothelioma Workshop (Ticketed Session) (ID 102)
- Event: WCLC 2019
- Type: Workshop
- Track: Mesothelioma
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/07/2019, 08:00 - 11:30, Interlaken (1988)
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WS02.12 - Translational Research MPM (Now Available) (ID 3841)
08:00 - 11:30 | Presenting Author(s): Maria J. Disselhorst
- Abstract
- Presentation
Abstract not provided
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