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H.J. Ross



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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-032 - A pilot single institution study of autologous tumor autophagosome (DRibble) vaccination with docetaxel in patients (pts) with stage IV non-small cell lung cancer (NSCLC) (ID 2486)

      09:30 - 09:30  |  Author(s): H.J. Ross

      • Abstract

      Background
      DRibbles are tumor-derived autophagosomes containing short-lived proteins (SLiPs) and defective ribosomal products (DRiPs). Vaccination with DRibbles produces tumor regression and provides cross-protection against syngeneic MCA sarcomas in preclinical models. Docetaxel can expose hidden tumor antigens and induces relative lymphopenia, potentially enhancing specific immune response. Sargramostim (GM-CSF) augments priming of tumor-specific T cells when administered at the site of DRibble vaccine in mice. This pilot study of autologous NSCLC DRibble vaccination with GM-CSF and docetaxel enrolled patients with advanced incurable NSCLC with malignant pleural effusion.

      Methods
      Pts had NSCLC with malignant pleural effusion, ECOG PS ≤ 2, and up to 2 prior chemotherapy regimens. Prior cancer-related vaccine therapy, active autoimmune disease, HIV, viral hepatitis, or chronic steroid use were not permitted. Pts with rapid clinical deterioration after enrollment were not eligible for vaccination. After informed consent, cells from malignant pleural fluid were cultured with bortezomib to block degradation of SLiPs and DRiPs and ammonium chloride to prevent lysosomal degradation of the autophagosome. DRibble vaccines were irradiated and passed sterility and endotoxin release criteria. Pts received docetaxel 75 mg/m[2] IV on day 1 and 29 for antitumor effect and to unmask tumor antigens and produce relative lymphopenia. Vaccination was scheduled for days 14, 43, 57, 71 and 85. GM-CSF (50 ug/d) was given via mini pump for 6d after each vaccination with immune monitoring pretreatment and at each vaccination.

      Results
      Six pts (3M, 3F, average age 65) with PS 1 and adenocarcinoma were enrolled. All received d1 docetaxel. Two did not receive further therapy due to clinical decline. Four pts were vaccinated (2-4 vaccines). One of 4 pts exhibited autologous tumor-specific immune response (IFN-γ, TNF-α, IL-5, IL-10) and 3 of 4 pts generated B cell responses (>5 fold specific antibody), with 1 patient not evaluable (Table 1). Figure 1

      Conclusion
      DRibble vaccine given with GM-CSF and chemotherapy is feasible. Small patient numbers preclude further conclusions. In order to translate this strategy to a larger number of pts in a more feasible population, we have developed an allogeneic DRibble vaccine from two NSCLC cell lines expressing at least 9 NCI-prioritized cancer antigens and including agonists for TLR 2, 3, 4, 7 & 9, HSPs and a dendritic cell-targeting molecule. A phase II trial of adjuvant DRibble vaccine alone or combined with GM-CSF or imiquimod is open in patients with definitively treated stage IIIA/B NSCLC. Support R21 CA123864-02 (WJU), R444 CA121612-01 (SA/TH) and Kuni Foundation (WJU).

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    P3.24 - Poster Session 3 - Supportive Care (ID 160)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-043 - Donor - derived metastatic lung cancer in a liver transplant recipient (ID 2858)

      09:30 - 09:30  |  Author(s): H.J. Ross

      • Abstract

      Background
      Malignancy after organ transplantation is generally the result of de-novo occurrence or recurrence of prior malignancy. Donor-related malignancy, defined as direct transmission of tumor from the donor organ or tumor arising from cells of donor origin in a recipient of a solid organ or hematopoietic stem cell transplant, is less common (0.02-0.2% of solid organ transplants). When organs from donors with known malignancy are used, the rate of transmission is up to 45%, with a mortality of 33-42%. We present the first case of donor-transmitted lung cancer in 550 liver transplants at Mayo Clinic Arizona.

      Methods
      Case report and literature review.

      Results
      A 69 year-old Caucasian male, former smoker, underwent deceased-donor liver transplantation for alcoholic cirrhosis and hepatocellular carcinoma. He was seen for a routine 4 month follow-up visit, had no complaints and was compliant with immunosuppression. Physical exam and laboratory tests were unremarkable. Abdominal CT revealed 3 small, solid, indeterminate liver masses. Follow-up MRI 6 weeks later demonstrated an increase in number and size of liver lesions. US-guided biopsy revealed poorly differentiated carcinoma most consistent with non-small cell carcinoma of the lung, with a minor component of small cell carcinoma. On PET-CT, the abnormal uptake was limited solely to the liver. Suspicion of donor-transmitted malignancy arose. The donor was a 50 year-old man, with history of alcohol and nicotine dependence (>20 pack/year), without history of malignancy. Chest x-ray, bronchoscopy and surgical lung examination, performed as part of procurement protocol, were normal. No other organ from this donor was transplanted. A PCR-panel of markers that recognize highly variable regions of DNA was used to compare donor liver tissue to the tumor and recipient liver tissue. Results confirmed cancer cells were of donor origin. Cancer was confined to the donor organ, but the patient could not undergo graft removal and re-transplantation. Immunosuppression was reduced, and chemotherapy (etoposide & carboplatin) was begun with initial response. Progression of metastatic liver disease led to second-line therapy with erlotinib. Unfortunately, patient succumbed shortly thereafter.

      Conclusion
      Donor-derived bronchogenic carcinoma after solid organ transplantation is extremely rare. One series reported lung cancer in 9 of 3374 patients (0.3%) transplanted over a 15 year period. Of these 9 patients, 3 patients had a kidney transplant, 3 had liver transplant, 2 had heart transplant and 1 had lung transplant. Treatment includes reduction/discontinuation of immunosuppression, chemotherapy and/or radiation therapy as appropriate, as well as removal of the transplanted organ and re-transplantation when feasible. In the present case we hypothesize that the donor had an undiagnosed lung cancer with subclinical hepatic metastases transmitted to our patient at the time of liver transplantation. Donor-derived lung cancer is extremely rare and can lead to significant morbidity and mortality. Proper diagnosis of donor origin is critical since it has a significant impact on management of these patients.