An Abscopal Response to Radiation and Ipilimumab in a Patient with Metastatic Non–Small Cell Lung Cancer

Ipilimumab and local radiotherapy result in an abscopal response. PET imaging and select fused PET/CT axial images from August 2012 (left) and January 2013 (right) are displayed. The axial images in the second row reveal the hypermetabolic liver lesion that was targeted and responded to radiotherapy (white arrows, second row). An abscopal response was seen in a left lower lobe lung lesion (white arrows, third row) and a left sacral lesion (white arrows, bottom row). A mixed response was seen in the hilar/mediastinal lymph nodes (striped arrows, third row).

Treatment timeline and the absolute peripheral blood cell counts. A detailed clinical timeline is displayed (A, top). A PET/CT on June 8, 2012, showed disease progression, prompting a change in the patient's chemotherapy regimen. On June 15, 2012, the patient was started on a chemotherapy regimen containing gemcitabine and vinorelbine. The green marker indicates the treatment timeline for gemcitabine and vinorelbine (A, top). A repeat PET/CT on August 6, 2012, showed continued disease progression. From August 22, 2012, to August 31, 2012, the patient was treated with concurrent radiotherapy (RT) and ipilimumab. Afterward, he received three additional cycles of ipilimumab alone. The blue marker indicates the treatment timeline for radiotherapy and ipilimumab [A (top) and B], and data plotted to the right of the vertical dashed line in each graph represents postinitiation of radiotherapy and ipilimumab treatment [A (bottom three graphs) and B]. The final dose of ipilimumab was given on October 26, 2012. Imaging on November 8, 2012 (CT of the chest, abdomen, and pelvis) and January 17, 2013 (PET/CT), showed significant treatment responses. During the course of treatment, the patient had serial blood draws. The results of the peripheral absolute blood cell counts [white blood cells (WBC), absolute leukocyte count (ALC), and absolute eosinophil count (AEC)] are displayed as number of cells (×10³) per μL of whole blood (A, bottom three graphs), in accordance with the aforementioned treatment timeline (A, top). A dramatic drop in carcinoembryonic antigen levels (a nonspecific tumor marker) was observed after treatment with radiotherapy and ipilimumab (B). The marker peaked at 119.6 ng/mL (normal levels 0–5 ng/mL) on September 7, 2012, showing a dramatic drop to 5.8 ng/mL on October 26, 2012, and thereafter was maintained at normal levels.

Enhanced tumor-infiltrating lymphocytes in an abscopal lesion. A treatment-naïve left supraclavicular nodal metastasis was excised in 2010 and an adjacent nonirradiated nodal metastasis was excised in 2013 (following treatment with ipilimumab and local radiotherapy). The immunologic characteristics of the two specimens were compared (A). A hematoxylin and eosin (H&E) stain showed lymphocytic infiltration largely confined to perivascular areas in the 2010 biopsy specimen (A, top left–black arrow), whereas lymphocyte-infiltrated tumor cells nests in the 2013 biopsy specimen (A, top right–white arrow). Rare CD8⁺ cells were present in the 2010 specimen (A, middle left). However, a marked increase in CD8⁺ and TIA⁺ (a marker for cytotoxic granules) cells was present in the 2013 specimen (A, middle right). The inset shows TIA-1⁺ cells directly interacting with tumor cells (A, bottom right). Cells were counted in 10 randomly selected high-power fields (HPF; B). CD8⁺ cells were significantly increased (P < 0.0001) in the biopsy from 2013. FoxP3⁺ cells also increased (P < 0.05), but the ratio of CD8⁺/FoxP3⁺ cells was higher in the 2013 specimen.