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R. Mason



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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-044c - Neurological Complications Following Treatment with Anti-PD1 Immune Checkpoint Inhibitors (ID 9213)

      09:30 - 16:00  |  Author(s): R. Mason

      • Abstract
      • Slides

      Background:
      With increasing use of single agent and combination immune checkpoint inhibitors in non-small cell lung cancer (NSCLC), a wide spectrum of immune related adverse effects (irAEs) are posing new challenges for treating physicians.

      Method:
      We report 3 patients with NSCLC, developing neurological autoimmune toxicities on treatment with Nivolumab.

      Result:
      Patient 1 was a 66 years old man diagnosed in 2013 with a T1N0M1 adenocarcinoma and a solitary cerebral metastasis treated with resection of both lesions and post-operative whole brain radiotherapy. In 2015 he developed metastatic disease and was treated in the KEYNOTE-024 trial. Randomised to chemotherapy he developed progressive disease after 18 weeks and crossed over to Pembrolizumab. Following his second cycle the patient developed acute encephalopathy, confirmed on EEG, peripheral sensory neuropathy and related gait disturbance. He responded to high dose methylprednisone with a complete resolution of symptoms. Patient 2 was a 61 year old man treated with 2[nd] line Nivolumab. After four cycles he developed right ptosis, blurred vision, dysarthria, dysphonia, dysphagia, myositis and grade 2 hepatitis. Electromyogram showed fatiguing with repetitive stimulation. A diagnosis of Nivolumab induced myasthenia gravis like syndrome was made. This responded to intravenous immunoglobulin, pyridostigmine and methylprednisolone with complete resolution of symptoms. Patient 3, a 61 year old female diagnosed with resected T2N2 lung adenocarcinoma in 2010 developed metastatic disease treated in 2015 with 1[st] and 2[nd] line chemotherapy. On progression she received Nivolumab. Autoimmune thyroiditis and hypothyroidism developed after 2 cycles followed by dysarthria and dysphonia. Initially diagnosed as a CVA on MR imaging, her symptoms worsened over two weeks with the onset of dysphagia, bilateral facial weakness and tongue atrophy. She was diagnosed with myasthenia gravis like syndrome, treated with pyridostigmine and immunoglobulin and subsequently plasmaphoresis and glucocorticoids with a moderate improvement in speech, facial movements and dysphagia. EMG and nerve conduction studies suggested a likely neuromuscular junction disorder. In all cases laboratory investigations, including auto-antibody screens, and imaging were of no value in establishing the diagnosis. All three patients have had near complete tumour responses on follow-up imaging despite discontinuation of therapy.

      Conclusion:
      Although relatively rare, these cases demonstrate the variety of presentations possible with neurological irAEs. Early recognition and treatment with immunosuppressive agents is essential to avoiding long term sequelae. The remarkable responses and survival seen in these cases indicate the need for further research to define the optimal treatment duration with checkpoint inhibitors in NSCLC.

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P2.07-032 - Outcomes of Nivolumab in Metastatic NSCLC Patients via the Access Program Across Multiple Tertiary Oncology Centres. (ID 9298)

      09:30 - 16:00  |  Author(s): R. Mason

      • Abstract
      • Slides

      Background:
      Immune checkpoint inhibitors are the standard of care for non-small cell lung cancer (NSCLC) patients following first line therapy. There is limited information available on the outcomes of patients receiving these therapies for NSCLC outside of a clinical trial.

      Method:
      We retrospectively collected data from patients who received Nivolumab for advanced NSCLC on the Bristol-Myers Squibb (BMS) Access Program across four tertiary oncology institutions in Brisbane, Australia, to analyse their outcomes in a real-world setting, and compare these outcomes to those in Phase III randomised clinical trials.

      Result:
      85 patients were enrolled to this Ethics Committee approved audit - 32 females (37.6%); 53 males (62.4%); 54, PS 0-1 (63.5%); 30, PS 2-3 (35.3%); median age 67 yrs (range 42-84). 84 patients were evaluable for progression. 20% (17/84) of patients had a radiological partial response (PR) during the course of their treatment, and an additional 22.4% (19/84) patients had stable disease (SD) as their best response. In PS 0-1, 24% (13/54) had a PR, compared with only 10% (3/30) in PS 2-3 patients. The overall median progression-free survival (PFS) was 1.8 months, being 2.7 months in PS 0-1 versus 1.2 months in PS 2-3 patients. Median overall survival (OS) was 5.9 months; 6.5 months in PS 0-1 versus 2.3 months in PS 2-3 patients. Median OS for adenocarcinoma was 6.2 months, versus 4.7 months for squamous cell carcinoma. At 12 months after initiation of nivolumab 34% of patients were alive; 44% PS 0-1 versus 16% PS 2-3 patients. Grade 3 or 4 treatment related adverse events were observed in 10% of patients. Analysis of the prognostic relevance of routine haematological and biochemical parameters is ongoing.

      Conclusion:
      Nivolumab has clinically significant long term benefits in the treatment of relapsed NSCLC with 12 month survival rates in keeping with clinical trials in PS 0-1 patients. The development of predictive biomarkers remains central to identifying those patients, particularly with poor performance, most likely to benefit from immune checkpoint inhibitors.

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